intro to nervous system cell physiology 101, part 1: demystifying the neuron || s1e4

[Music] hello and welcome to intro 101 my name is Kris  and I am your neuroscience and psychology graduate student assistant I'm here to assist you with the  related science Basics that you interact with on a daily basis my goal for doing this is to help you  start or continue to build a foundation in human biology and physiology ology that can better help  you engage with the information you consume from your favorite health and wellness Educators and  influencers much like the way a graduate a

ssistant helps prepare intro students so they can better  engage with lectures delivered by their professors or maybe you're here because you just like a  better idea of what's going on under the lid either way grab a notepad and pencil and beverage  of choice and stick with me for the next forever minutes because today we embark on a Fabulous  Adventure into the cell cellular level of the nervous system today's episode is intro to nervous  system cell physiology 101 part one it is entirely devo

ted to the beautiful complex and very chatty  neuron we'll go over basic cell structure anatomy and function including neural communication  and its role in the production and release of neurotransmitters we'll look at a few different  kinds of neurotransmitters and where they project in the central nervous system and we'll also cover  some of the different types of neurons and where in the body they live you may be surprised I'll  introduce you to some inspiring neurobiologists and neuroscienti

sts both past and present who have  made incredible contributions to our understanding of this Mighty cell before we start I'd like  to respectfully acknowledge with much gratitude that intro 101 is recorded on the unseated and  ancestral territories of the Kwantlen, Katzie, Matsqui, and Semiahmoo First Nations additionally  we at intro 101 believe wholeheartedly that science is for everybody in fact the richness  complexity and strength of scientific research is astronomically improved by the i

nclusion of many  varied voices to ensure everybody has access to education research resources and representation  across scientific Fields the world over I will be sharing organizations in the show notes that  provide access to stem education opportunities and research resources and ask that you check  them out and support them in any way that you can please donate share their work on your social  media networks or maybe volunteer your time to help them if you already Advocate or generate  oppo

rtunities that provide Equitable access to stem education and resources within your own  communities or support other stem organizations not listed here do let us know about them in the  comments below so others can contribute as they are able all right welcome to class let's crack  on with nervous system cell physiology 101 Part part one the neuron I'm very excited about all the  things I want to share with you today I'm almost overwhelmed by choice as to where to begin we  really get into the

details today so this episode is a little bit like a Choose Your Own Adventure  book I recap some of the major discussion sections so if you just want the light version of neuron  physiology you can choose to just watch or listen to the Recaps if you love revelling in the minutia  or just really want a deeper understanding of what these cells do follow along the whole way through  or mix it up you have options so we'll start with a recap of some of the general facts you learned  from the previou

s episodes if you remember your nervous system is one of 11 body systems that work  together to maintain homeostasis in your body if you're new to this Channel and new to the nervous  system please check out the previous episodes to get familiar with what homeostasis is and to get  a broad understanding of the nervous system and its many parts okay so also a reminder that  the nervous system is one of two regulatory body systems the endocrine system being the other  nervous system tissue is made

up of particular types of cells the ones we hear about the most are  the stars of today's episode neurons neurons are special because they send and receive chemical  and electrical messages signaling to the body and brain to take some kind of action there are  many different kinds of neurons throughout the nervous system and they are highly specialized  meaning they carry out functions specific to their type the adult human nervous system has  somewhere around 86 billion neurons in the brain 50

0,000 motor neurons in the errant division of  the peripheral nervous system 10 million Sensory neurons in the afer division of the peripheral  nervous system and somewhere between 200 and 600 million neurons in the enteric nervous system  system which if you remember from the nervous system episode is located in the wall of your  gastrointestinal tract yes you have millions of neurons outside of your brain for a long time it  was believed that the brain contained 100 billion neurons but neurosc

ientist Susanna herculano  husel figured out a more accurate way to count them than had been previously attempted in fact  she couldn't find where the original count of 100 billion neurons came from so she devised an  experiment by which she dissolved a human brain into what she calls brain soup and from that she  was able to identify and count neuronal nuclei and she and her colleagues counted 86 billion neurons  in the brain on average during the same process she was able to count non neuron n

uclei as well  which was roughly the same number as neurons and that too is wildly less than what was originally  hypothesized we'll get to nervous system cells that aren't neurons in the next episode we we  can't really begin to discuss neurons without first mentioning two men who share a Nobel  Prize for their independent contributions to our understanding of neuronal morphology they are  Camillo Golgi and Santiago Ramon Y Cajal you'll recognize Camillo Golgi from the last episode  on Cell phy

siology as the discoverer of the Golgi complex also called Golgi apparatus though  even having an important organelle named after him slightly pales in comparison to perhaps his  most beloved contribution to science and that was the invention of a staining method that rendered  the structure of individual neurons visible for the first time named of course the GGI stain now  though GGI made these really important discoveries he also championed a theory about how neurons  function that didn't pan

out to be accurate he believed that neurons fused together to form a  kind of net of nerves that operated as one whole unit rather than each individual neuron operating  on its own this is where Ramon y Cajal enters the scene he refuted Golgi's Theory ironically by  using the GG stain method to study the nervous tissue of many organisms including human and he  found that neurons are indeed their own contain units and communicate to each other albeit  at an extremely close range more on that in a

bit but do take a minute to appreciate these  two important historical figures both GUI and Ramon Y Cajal included detailed drawings of  neurons while documenting their findings in fact Ramon Y Cajal was an artist before he was  a scientist I can't imagine what it would have been like to be one of the first people to see a  neuron especially Through The Eyes of an artist there is something about both Golgi and Ramon Y  Cajal's renderings that bears witness to whatever awe and wonder they may ha

ve experienced when  they first laid eyes on these Beauties their illustrations look simultaneously other worldly  and familiar like something you might find growing in the Shady underbelly of a forest I almost  wish I hadn't seen a modern graphic rendering of a neuron before I saw GOI and Ramon kajal's  illustrations some of their work is beautifully meticulous and yet some also seem a bit rough  and rushed but in those you can almost sense the Magic in urgency of feverishly trying to capture 

a moment of Discovery I've posted a link in the show notes below that has a gallery devoted to  the illustrations of both of these men if you take a minute to look at their illustrations try  to imagine what it would be like to be them seeing these tiny Fantastical looking cells for the first  time so what do these Fantastical neurons look like well as I've mentioned their shape and size  vary by type the multi-polar neuron is the most abundant and likely most represented in typical  diagrams of

a single neuron our graphic represent presents a multi-polar neuron which seems to  be the most common type found in the central nervous system it has a tree likee structure with  what looks like branches extending from a cell body a longer thin trunk projecting from the cell  body and Roots protruding from the bottom of that trunk the cell body is called the Soma and its  intracellular physiology is very much like that described in the previous episode on typical cell  physiology with the addi

tion of granules called nil bodies which is kind of like additional rough  endoplasmic reticulum to Aid in the abundance of proteins the soma needs to produce otherwise  it has a nucleus containing genetic material and organelle suspended in cytosol like most  other cell bodies the Soma carries out basic cell functions but on top of that it carries out  all sorts of business specific to nervous system function this will get clearer as we get more  acquainted with the neuron's main job and that i

s cell cell communication by a process called  neurotransmission but to give you an idea of the amount of activity going on we can look at  the kind of energy neurons consume in just a resting state and for that we turn to a study by  zuu and colleagues they were able to calculate that a single cortical neuron so a neuron in the  cortex of the brain like our example so a single cortical neuron utilizes approximately 4.7 billion  ATP molecules per second in a resting human brain and by resting br

ain they mean the brain activity  of a human in a fully relaxed condition can you imagine what the metabolic output would be if  you were being chased by a bear it would be a lot okay so what's going on in the cell body that  requires so much energy if you remember from the last episode one of the jobs mitochondria are  tasked with is making ATP which is the fuel cells need to do their business so in a kind of  cellular version of an internal return the cell needs to make a ton of ATP to not onl

y provide  enough fuel to burn 4.7 billion molecules of it per neuron per second it also has to make enough  fuel to keep making and metabolizing ATP consider the amount of mitochondria needed to produce  that much ATP so as you can imagine there is an abundance of mitochondria in a typical  neuron the cell also produces and packages hundreds of different proteins each with its own  specific supportive function it also manufactures different types of chemical molecules that it  needs to transpor

t to the very end of the neuron and those determine the type of signal being sent  to the next neuron we'll get into how all of this plays out in a minute but for now know that the  Soma is a hub of manufacturing activity that takes a ridiculous amount of energy to produce organize  synthesize and transport all the goods needed to do its business okay now the tree like appendages  branching off of the Soma are called dendrites the word dendrite comes from the Greek word dendron  which means trea

t not all neurons have dendrites but those that do have Junctions at the ends that  receive signals from other neurons the dendrite branches also have many tiny thorn-like structures  attached to them called spines dendritic spines like the dendritic Junctions also receive  signals from other neurons expanding its own neurons ability to receive multiple signals it's  been suggested that dendritic spines attract a specific type of signal called excitatory input  more on that later on and addition

ally spines also appear to rapidly change in shape and  number during neuronal activity this will be important to remember when we get to discussions  on neuroplasticity in future episodes okay moving on to another side of the Soma where there is  a protruding thin trunk this trunk is called the axon also called a nerve fiber that projects  to other parts of the brain and body at varying lengths depending on where in the nervous system  it is it has a very important role in passing along or tran

smitting a signal to the next neuron  so the dendrites are signal receivers and the axon is a signal transmitter the outer surface of  some axons is covered in a fatty substance called myelin and that has a specific purpose related  to insulating the signal that is traveling along the axon more on that in a minute the axon's  intercellular physiology is incredibly Dynamic and involved in transporting molecular cargo from  and to the Soma because the end of the axon which is the end of the neuron

can be quite a distance  from the cell body or Soma there needs to be a way to get things that are produced in the Soma to  the other end of the neuron this is accomplished by a process called axoplasmic transport and  the best way I can explain what this is is to ask you to imagine a tiny headless protein with  legs feet and arms carrying a giant sack full of goods along a microtubule to the end of the axon  they do this at a speed of roughly 500 mm per day if you're unsure of what a microtubu

le is it's a  long thin tubular track with loads of functions but see the previous episode on Cell physiology  for a more in-depth description so tiny headless proteins transport cargo to the end of the axon  but that's not all sometimes bits need to travel from the end of the axon back to the Soma and this  process is called retrograde axoplasmic transport but same basic principle little headless dude  walking cargo along a microtubule only retrograde transport takes place at a much slower Pace

I kid  you not this is how happening inside your body right now so what's at the end of the axon that  has so much business going on it needs to receive and send cargo the end of an axon can Branch  off into root-like structures and at the ends of those roots are bulbs called terminal buttons  or I've also heard them called synaptic buttons inside the terminal buttons are where chemicals  called neurotransmitters are synthesized stored and released into the extracellular space between  the term

inal button and the of another neuron it's trying to communicate with neurotransmitters  are also called chemical messages because they are chemical molecules this chemical transmission  is how the signal is passed on to the next neuron this process is called neurotransmission and this  whole Space is called the synapse so the synapse includes the Press synaptic terminal button the  post synaptic dendrite and the space in between them which is called the synaptic Clift so you  might be wondering

wondering what material needs to be transported up and down the axon between  the Soma and the terminal button well the terminal button contains large and small vesicles called  synaptic vesicles which are like round membranous sacks that look like Escape pods the small  synaptic vesicles contain neurotransmitters the large synaptic vesicles contain different types of  peptides the Soma produces these large and small vesicle sacs and the peptides and it makes the  enzymes needed to synthesize n

eurotransmitters and the tiny protein dudes are transporting all  of this from the Soma to the terminal button by axoplasmic transport important to note is that  every part of the neuron is contained inside a plasma membrane so even though it's a strange  shape the plasma membrane surrounds the whole thing so dendrites axons and terminal buttons  too not just the Soma the plasma membrane is incredibly important in cell communication but  more on that in a moment okay so quick recap the typical n

euron looks a bit like a tree with  dendrites branching off the Soma the dendrites have spines attached to them and that enhances the  cell's ability to pick up signals from neighboring neurons the Soma is the cell body and it is a  hive of manufacturing activity related to basic cell function and neurotransmission protruding  from the Soma is a long thin trunk-like structure called called the axon the axon is a nerve fiber  of varying lengths and projects to both the brain and body depending on

the type of neuron the  outside of the neuron transmits the electrical communication signal and some axons are covered  in fatty myelin that helps insulate and speed up the signal inside the axon a wondrous process  called axoplasmic transport is taking place and that is when tiny proteins carry cargo along  microtubules that run the length of the axon from the Soma to the axon's terminal buttons sum  of that cargo is small and large synaptic vesicles small synaptic vesicles contain neurotransm

itters  and large synaptic vesicles contain peptides most of which is manufactured in the Soma when they  reach the terminal buttons of the synapse also called pre- synaptic button the synaptic vesicles  are stored and await the electrical signal that is their cue to release their contents into  the synaptic CFT where they will find their way to the post synaptic dendrite and the process  begins again at the next neuron and all of this is contained within the borders of a plasma membrane  next w

e're going to look at the physiology of neurotransmission I think the best way to get  better acquainted with the physiology and function of a multi-polar neuron is to follow a signal from  the receiving end so the receiving post synaptic dendrites all the way to the Rel releasing end  of the pr synaptic buttons into the synaptic C where the signal is then passed on chemically  to the next post synaptic dendrites before we get into the minutia of neurotransmission it's  probably a good idea to g

ive you some general context as to the purpose of neurotransmission  I've said this in other episodes and I'll say it again here it's easy to lose sight of the body's  homeostatic goals when we talk about one tiny part in a siloed manner I'm about to give you an  example of cell communication in one neuron but in reality billions of neurons can be communicating  at any one time and in a beautifully orchestrated Symphony of chemical and electrical currents that  initiate thoughts and actions and

beget behavior and memories and emotions and movement and so much  more there are roughly 100 quadrillion synaptic connections and any one neuron can be connected  to and communicated meeting with 5,000 to 10,000 other neurons this process neurotransmission is as  I've said a regulatory process your body relies on to keep it in Balance to keep it in homeostasis so  try to hold that bigger picture in mind as we get into the details so let's begin with our typical  neuron communicating to another

neuron the typical communication modality of a multi-polar neuron is  synaptic transmission so we're at the synapse now normally when we hear about neural communication  the phrasing can go something like neurons send electrical pulses or signals throughout the brain  and body to somewhere for the most part the signal is electric it has an electrical charge but the  space between the presynaptic button and the post synaptic dendrite called the synaptic cleft is two  larger space even though it's

incredibly tiny for an electrical current to directly leap across  so the pre synaptic side of the synapse changes the electrical signal to a chemical signal and it  does this by releasing neurotransmitters more on that when we get to the other side of the neuron  so the pre synaptic button has just released a load of chemical neurotransmitter molecules into  the fluid filled extracellular space that is the synaptic Clift they diffuse across the synaptic  Cliff to the post synaptic or receiving

dendroid this is where it all kicks off dendrites can be  smooth or they can have spines both are bordered by the cell's plasma membrane but this particular  area of the plasma membrane where the postsynaptic dendrite receives the neurotransmitter this  area is called post synaptic membrane this post synaptic membrane contains special proteins called  called receptor channels they're also called ionotropic receptors or lien gated receptors  but receptor channels is easier to say and also rememb

er so for now I'm going to refer to them as  receptor channels what makes them special is that they are protein units that contain an ion Channel  but also have receptors attached to them that unless activated keep the ion channels closed or  gated this receptor part of the unit has a special binding site that is designed specifically for  its partner neurotransmitter molecule when the neurotransmitter diffuses across the synaptic  cff it will bind with the receptor like a key to a lock no other

type of neurotransmitter can  bind to that receptor when the neurotransmitter molecules bind to each available receptor those  receptors activate and open the Ion channel it is attached to in other words these receptor  channels are chemically gated ion channels which means the signal the dendrite is receiving is in  its chemical form and can only be in chemical form there may be lots of reasons for this but I think  it helps keep the signal going in One Direction because once it's past this po

int it converts to  an electrical form and that electrical form can't manipulate these Gates a quick reminder from the  previous episode on Cell physiology is that ion channels are proteins in the plasma membrane that  allow ions to cross the membrane's phospholipid bil layer because ions are water soluble and  cannot pass through the lipid membrane on their own okay so the neurotransmitter chemical molecule  has bound to the receptor Channel opening up the Ion channel here's where it gets very

persnickety  how the signal converts from chemical back to electrical form depends on a few things in general  what happens when the ION channel opens is that it allows ions to enter the intracellular space  that will shift the electrical charge within the cell either positively or negatively if it shifts  the charge positively and to a specific voltage threshold then we've got ourselves the signal  that will make it to the end of the neuron if it doesn't quite reach that threshold or if the  ch

arge is shifted negatively making it even less likely it will reach the threshold then this is  where the signal ends there is so much happening at this juncture that involves an intense amount  of scientific understanding I don't want to bury you in detail but I'll get into it as best as  I can because we've looked at body physiology down to the cellular and molecular level so far  in this series but this next bit will take us to Atomic levels I told you in the first episode that  our bodies re

cruit even the tiniest atoms to help us maintain homeostasis and this is one very good  example at how it achieves that so to set up the next level of detail it's important to understand  that plasma membranes are electrically polarized which means positively and negatively charged ions  ions are electrically charged atoms they live on either side of the membrane in the intracellular  and extracellular fluid the intracellular side of the membrane is slightly more negatively charged  than the ext

racellular side when the cell is at rest this means it has slightly more negative ions  on the inside of the cell than the extracellular side when this Dynamic changes the polarization of  the membrane changes and that is called membrane potential if an influx of positively charged ions  cross the membrane into the intracellular space the membrane depolarizes if more negative ions  enter the intracellular space or positive ions leave it becomes even more negatively charged  and the membrane hype

rpolarizes okay now park that for a minute another important thing to know  is that when a neuron is not active it is at rest when it is at rest the electrical charge of the  membrane is polarized at roughly -70 millivolts this is called resting potential this is the  set point which determines whether the membrane depolarizes or hyperpolarizes if you remember  a set point is part of the homeostatic feedback loop when it shifts too far from its range the  body initiates activity that will bring

it back to its set point range so when more positive ions  enter the cell it becomes less polarized than - 70 M the charge moves closer to 0 molt for instance  a signal of small magnitude May shift the charge up to - 60 M when it's hyperpolarized the charge  moves even farther from 0 molts than - 70 molts so maybe it'll reach -80 molt you can park this  for a few minutes too so let's rewind back to the post synaptic dendrite where neurotransmitter  molecules have unlocked the ion channels and le

t's approach how the signal converts from chemical  back to electrical form with a little more detail now the how is going to depend on a few things  one is the type of neurotransmitter and another is the ion Channel it opens and the particular  ions that channel allows into the cell as for types of neurotransmitters there are excitatory  neurotransmitters and inhibitory neurotransmitters excitatory neurotransmitters open ion channels  that allow the passage of sodium ions across the membrane in

to the post synaptic neuron sodium  is a positively charged ion so what's going to happen to the intracellular side of the membrane  when loads of positive ions enter it depolarizes because now there are more positive ions inside  the cell when it becomes depolarized it is more likely to create a potential a potential is stored  energy and if an abundance of positively charged ions enter the intracellular space it can change  the voltage of the cell from resting potential to an action potential

a little bit further  down the neuron and the action potential is what keeps the signal moving an excitatory  potential at an excitatory synapse is known as an excitatory post synaptic potential or epsp  inhibitory neurotransmitters open ion channels that either allow more positive ions to leave  the membrane or more negative ions to enter the cell increasing the negative charge inside this is  called hyperpolarization and it pretty much kills any chance that there will be enough potential  to k

eep the signal moving the in inhibitory neurotransmitter inhibits further activity and  this is aptly called inhibitory postsynaptic potential or ipsp there are many instances  when this is a good thing please don't think that because a signal terminates that something is  wrong we don't want to be firing all the time for example what prevents alertness from becoming  hypervigilance and anxiousness are inhibitory neurotransmitters the most most abundant  excitatory neurotransmitter is glutamate

glutamate almost always produces excitatory potentials or  epsps the main inhibitory neurotransmitter is gamma Amino amino butc acid gamma gamma amino butc  acid gamma amino butc acid also known as GABA it's GABA just it's GABA. GABA always produces  inhibitory potentials or ipsps we'll look at these and other neurotransmitters in a few  minutes an excitatory potential at one synapse may not depolarize a post synaptic dendrite  membrane enough to create an action potential that moves the signal

along but all of the neurons  dendrites and dendritic spines together receive a ton of inputs at the same time and the summation  of simultaneous excitatory and inhibitory inputs results in a total post synaptic potential since  excitatory potentials are more likely to create enough potential to move the signal along we'll  assume that our neuron example received a total post synaptic potential that is excitatory and  add a large enough magnitude that we can follow it along the neuron so once ex

citatory potential  is established at the post synaptic area of the membrane the resulting ion difference inside and  out outside of the membrane creates a current of ion movement along the resting membrane changing  the membrane potential as it flows this is called a graded potential and it can sort of lose its  o as it travels along the membrane away from its trigger point at the post synaptic dendrite but  if the magnitude of the excitatory potential is large enough so a high enough voltage i

t can  create a graded potential that can depolarize the m all the way through the Som to a pivotal  area at the beginning of the axon called the axon hillock the axon hillock has loads of sodium  ion channels only these ion channels are activated By changes in electrical membrane potential  and this dense patch of sodium ion channels makes the axon hillock extremely sensitive to  changes in membrane potential if the graded potential so this flow of electrical current  depolarizing the membrane

as it travels from dendrite through the Soma if it reaches the axon  hillock on the other side of the Soma it still has a magnitude of voltage that meets the axon  hilx threshold which is about minus 55 molts this dense little patch of sodium ion channels open  and an explosive influx of sodium ions flood the intracellular space and supercharge the current  creating the all-important action potential once the action potential is triggered no other event  is required to blast that supercharged cu

rrent down the axon to the terminal buttons and launch  neurotransmitters into the synaptic cleft when you hear terminology like neurons fire or Spike that  is referring to the moment the action potential is triggered an important note about the action  potential threshold is that the graded potential must hit that threshold of - 55 millivolts it's  called The All or Nothing phenomenon if it's even a little less the action potential will not be  triggered and the neuron will not fire but if it h

its - 55 millivolts the sodium ion channels fly  open and the influx of sodium changes the voltage to somewhere near plus 30 millivolts that's a  difference of 85 millivolts from threshold and that's 100 mol difference from resting potential  if you need a visual to lock in this all or none phenomena think of Marty McFly and a DeLorean  with a flux capacitor if he can get the delorean to a threshold of 88 mph there's an electrical  explosion and he Rockets into another time it can't be less than

88 mph that is the threshold  with the greater potential traveling along your neurons it has to meet minus 55 millivolts and  it has to be at least that voltage at the axon hillock for the action potential to rocket down  the axon it won't rocket us into another time but you'll move a muscle or blink actually I mean  I guess the I guess technically a reflex arc happens faster than the event it's responding to  can register in our conscious awareness so maybe some of our neurons do fire into the

future  if present time exists only at the moment we perceive it I don't know what do you think leave a  comment below it's just for fun so please be kind I kind of like the idea that part of us can live  in the future like baby time Lords okay moving on so what's happening along the axon while this  supercharged current is rocketing to its end well once the action potential is triggered at the axon  hillock the current is propelled down the axon by way of one of two methods contiguous or salta

tory  conduction contiguous conduction involves axons that are not myelinated so these are axons  that are not insulated with fatty cells and this conduction follows a very similar pattern  to the flow of current we find in the graded potential mentioned earlier it requires the same  action of an influx of sodium ions moving into the intracellular space of the axon through voltage  gated sodium ion channels Shifting the charge to a significantly more positive charge and thereby  depolarizing the

membrane one patch of membrane at a time all the way down the axon what makes  the continuous conduction of an action potential different from a graded potential triggered at  the excitatory synapse is that it doesn't lose any oomph it maintains its momentum and it does  this because what's traveling down the axon isn't actually the same action potential as the initial  trigger at the ax and helic new action potentials are being triggered at sequential sections of  membrane all the way down the

axon contiguous means in sequence and that's what's happening  Action potentials are igniting new identical Action potentials in sequential patches of  plasma membrane along the axon by way of an influx of sodium ions through voltage gated  ion channels at each patch this depolarizes the membrane to a voltage threshold that launches  another action potential in the next section and so on and so on from beginning to the end of  the axon what keeps the action potential going in One Direction well

once the next section of  membrane becomes activated the previous section returns to its resting state and when it returns  to its resting state it enters something called a refractory period this means that when the next  action potential is generated and depolarization of the membrane happens the voltage gated sodium  ion channels in the previously active section of the membrane remain closed so they cannot  be triggered to open again until the whole cell returns to resting state and resets t

hem so  both contiguous and saltatory conduction can only happen in One Direction now saltatory conduction  involves myelinated axons if you remember from earlier our example of a multipolar neuron is  covered in a fatty substance called myelin and it acts as an insulator if you recall I are water  soluble and can't cross through liquid layers without assistance so ions cannot pass into or out  of myelin as there are no ion channels in myelin in the peripheral nervous system these myelin  cells

are called Schwann cells in the central nervous system they're called oligodendrocytes  since our sample neuron is in the central nervous system we'll continue the Journey of the action  potential as though the milin is alod dendrites to be clear is not part of the neuron it's like  sheets of lipid membrane that are wrapped around the axon like a Swiss roll but more like a Swiss  roll Zilla because it can have up to 300 lipid sheet layers and it does this in sections all  along the axon Schwan c

ells are individual Swiss rollik cells independent of each other lined up  along the axon alod dendrites are cells with many arms that have Swiss roll like hands at the end  of them called myelin sheath and the arms sort of reach out and wrap the myelin Swiss roll hands  around the axons one oligodendrocyte can reach out and wrap around many parts of one axon and also to  multiple other axons in the vicinity these myelin Swiss roll hands are not buted up right next  to each other there's a littl

e space in between each of them and those spaces are called nodes of  ronier and those spaces or nodes are bare naked axon completely exposed to the extracellular fluid  these exposed bits of axon are important because that is where each action potential is initiated  down the melinated axon these nodes are packed with sodium ion channels that get activated as  the current flows down the axon I say flow but it more like jumps over myin to the next node the  word saltatory comes from the Latin wo

rd salus which means to jump so saltatory conduction is  an electrical charge jumping from one node to the next and this significantly increases the speed of  the electrical pulse to about 50 times faster than contiguous conduction this is important for neural  Pathways that need to respond quickly to input like consider your visual Pathways there is a  bundle of axons that runs from the neurons in your retina to the back of your brain and it's called  the optic nerve and it contains roughly 1 m

illion melinated axons because that info has to zip zip  at lightening speeds to where image processors live so you can make sense of those inputs by  turning them into forms you can recognize if those were unmated axons theoretically our visual  processing speeds would probably lag quite a bit because it would take much longer for input to  reach the visual processing brain areas in reality deated axons that are supposed to be melinated  are implicated in a number of neurodegenerative diseases

in the optic nerve deterioration of myin  may play a role in the development of glaucoma so myin is very important and we'll talk more about  the cell that form it so alod dendrites and Schwan cells in more detail in the next episode so just  now I gave you an example of melinated axons and why they need to be melinated but what about  neurons with unmyelinated axons well unmyelinated neurons are present in both the peripheral  and central nervous systems and an example of neurons that are unmat

ed are those involved in  your body's ability to sense pain brought on by damage to body tissue like a burn to the skin so  I'm not sure why those neurons need to be unmated you'd think you'd want faster processing speeds if  your skin is on fire but I guess there are other neurons receiving input that are melinated  and are already trying to put out the Flames before you're experiencing the full magnitude  of pain so I'm wondering if maybe the unmated neurons help slow or temper the magnitude o

f pain  experienced I don't know for certain that unmated neurons involved in pain processing are directly  involved in tempering immediate pain processing but it makes sense to me that they would slightly  delay the amount of pain processed perhaps to Aid and pain tolerance something to look into for  another time okay now there's another aspect to action potentials that provides another  layer of context to homeostasis of the cell if you remember from a few minutes ago I said the  resting memb

rane potential of the neuron is about -70 mols but when we get an excitatory potential  at a magnitude that depolarizes the cell to a threshold ofus 55 M at the axon hilic that creates  that action potential that zips down the axon so how does the cell close the loop and get back to  a resting state well while the action potential is happening there are a couple of things that kick  in just after the sodium ion channels fly open in response to depolarization the ion channels  are voltage gated a

nd oddly what makes them open also makes them close again only slower than  the speed of opening so the sodium ion Channel Gates fly open and loads of sodium flies into the  intracellular space but their ion channels start to close half a millisecond later preventing any  more sodium ions from entering the cell and the channels will stay closed until another action  potential is initiated the second thing that happens involves other ions that are at work one  of the other ions I want to draw you

r attention to is potassium pottassium ions are positively  charged ions that at resting state dominate the intracellular space as far as positive ions  go not enough to create depolarization because there are still more negative ions than positive  ions in the intracellular space potassium ions are also kind of like wandering free ions in  the plasma membrane they have both gated ion channels that are closed until activated as well  as a few special ion channels that are open all the time so ca

n leak into extracellular  space or not they're on their own Journey they're peaceloving rest promoting ions until an  action potential rips through the neuron blasting positively charged sodium ions into their space  with ions Opposites Attract and same Z's Propel so positive pottassium ions aren't super Keen  to stick around in spaces that get supercharged with an abundance of positive sodium ions because  they have the same electrical charge when the the membrane is at Peak potential after it

's reached  threshold gated potassium ion channels slowly open and potassium exits the cell to go I don't know  plant some peace in the extracellular space and when they do that it shifts the amount of positive  charge in the intracellular space and when that happens the membrane potential drops from Peak  to resting technically the membrane potential would eventually reach a resting state by the  sodium ion channels closing and potassium ions gradually leaking through its open channels into  th

e extracellular space but potassium having its own gated ion channels speeds up the process  in a kind of reverse graded potential on the extracellular side of the membrane this rushing  of potassium ions into the extracellular space is called potassium efux because both potassium  leaky channels and gated channels are open the e-lux of potassium is slightly more excessive than  necessary in effect hyperpolarizing the membrane so dipping below resting potential before it  normalizes again to res

ting potential so now we have a bunch of potassium ions in the  extracellular space and a bunch of sodium ions in the intracellular space so how does the  cell go back to its resting state concentrations of sodium and potassium on either side of the  cell membrane well the membrane has yet another protein embedded in its phospholipid bilayer  it's not an ion channel it's not a receptor it's a pump specifically a sodium potassium pump  for every three sodium ions it pumps back out of the cell it

pumps two potassium ions back into  the Cell It's relatively slow but eventually it will restore the ion concentrations on either  side of the membrane the neuron doesn't have to wait for the pump to completely restore these  concentrations before it can launch another action potential because there are still loads  of other sodium and pottassium ions on their respective sides of the membrane but it does  need to keep pumping to keep the concentrations at odds so more potassium inside than outsi

de  and more sodium outside than inside okay so so far we followed the signal from receiving  dendritic synapses all along the membrane to the axon hilic to transmitting down the axon and  now we are almost full circle at the synapse but before we get there what happens at the end of  the axon at the terminal buttons remember back to the dendrites where they received the signal in  chemical form and converted it to electrical form so how does the electrical form of the action  potential convert

back to chemical form before it's released into the synapse by press synaptic  neuron well when the action potential reaches the terminal end of the axon more ion channels  spring open only this time they're calcium channels in the terminal buttons we'll call them  the preseptic buttons for clarity the pre synaptic buttons contain synaptic vesicles remember the  tiny protein dude carrying vesicle sacks full of stuff produced in the Soma and transporting  them down microtubules to the pratic butt

ons in a process called axoplasmic transport those are the  synaptic vesicles contained in the Press synaptic button so the voltage gated calcium ion channels  in the buttons open and an influx of calcium ions enter the synaptic button and when that happens  it triggers an event called EXO cytosis that's when some of the vesicles fuse with the plasma  membrane so it becomes part of the membrane and all of its contents spill out into the synaptic  Clift those contents are neurotransmitters and th

ey diffuse across the synaptic Clift and we  start this process all over again at the post synaptic dendr some terminal buttons synapse with  dendrites and some synapse to the Som membrane in our example the pre synaptic button synapses with  post synaptic dendrit now I've just described a chemical syapse but there are also electrical  synapses not many but they are involved where synchronized neural firing is necessary for  instance they are most abundant in a part of the brain that secretes a

neuro hormone responsible  for controlling the reproductive system but it must do so in a distinct synchronized pattern  of secretion because the cells on the receiving end only respond to this pattern okay we've made  it all the way through the process of one neuron receiving excitatory input and firing an action  potential to its terminal end where it passed it on to the next neuron this was a lot of detailed  information so thank you for sticking with me but let's recap quickly before we look

at some of  the different kinds of neurotransmitters and what happens to them after they've done their business  in the synaptic C so to recap neurotransmission post synaptic dendrites receive an incoming  chemical neurotransmission that is either excitatory or inhibitory and it connects like a  key to a lock to receptor channels in the plasma membrane if it's an excitatory neurotransmitter it  unlocks sodium ion channels allowing an influx of positive sodium ions into the intracellular  space

which depolarizes the membrane and converts the chemical signal to electrical if it's  inhibitory positive potassium ions leave the cell or negatively charged chloride ions enter the cell  and hyperpolarizes the membrane and terminates the signal because the dendroides receive multiple  inputs the summation of inputs determines if the total membrane potential is excitatory or  inhibitory and if it produces an excitatory synaptic potential with a high enough magnitude  it begets a graded membrane

potential that should be strong enough to reach the axon hilic at  threshold which is- 55 MTS this then triggers loads of sodium ion channels to fly open and allow  an influx of sodium ions into the intracellular space rapidly depolarizing the membrane and  launching it down the axon either by unmyelinated contiguous conduction or melinated saltatory  conduction both require creating new action potentials along the axon at either sections of  the membrane or at nodes of exposed axon called node

s of ronier but once the action potential is  triggered it does not lose momentum it will fire the length of the axon to the terminal buttons  where it triggers calcium gated ion channels to open and cause an influx of calcium ions this  triggers vesicles to release neurotransmitter chemicals into the synaptic Clift and diffuse  across the cliff to the receiving post synaptic dendrites which converts it back to an electrical  signal and so on and so on until whatever actually needed to happen ha

ppens the neuron returns  to a resting state by way of potassium ions leaving the intracellular space after sodium ions  invade their space which repolarizes the membrane to a resting potential and eventually a sodium  potassium pump helps both types of ions find their way back home to their favorite side of  the membrane okay loves have a stretch hydrate because now we're going to look a little closer at  neurotransmitters and what their roles are Beyond propagating a signal to the next neuron

but first  we're going to look at what happens to them after they've done their business in the synaptic Clift  this part may seem like excessive detail but this very tiny Gap the synaptic CFT between neurons  is a most beloved space it's in this space where many therapeutic drugs and recreational drugs  SL drugs of abuse intentionally manipulate your brain chemistry sometimes for beneficial outcomes  other times not so much You may wish to know how and why this happens so after the pre synaptic

  button has released these neurotransmitters into the synaptic CFT and it is bound to the receptor  channels in the post synaptic membrane in order for another neurotransmission to happen  the previous neurotransmission needs to be inactivated by removing the neurotransmitter  from the synaptic CFT this happens a few different ways one is reuptake another is degradation by  enzymes and lastly it can just wander away from the synapse by way of diffusion reuptake is the  fastest and most efficien

t way and simply put the neurotransmitter is taken back up into the Pres  synaptic or terminal button to be recycled and restored in vesicles or demolished by enzymes  you may be wondering how it does this because the vesicle that housed this neural transmitter  fused with the pr synaptic button membrane so it's not going back into those vesicles well  much much like ion channels embedded in the post synaptic plasma membrane allow ions into  and out of the cell the pre synaptic button has transp

orter molecules embedded in the plasma  membrane that draws the neurotransmitter back into the intracellular space the terminal  button and they are recycled and repackaged into vesicles you may recognize the word reuptake  because a certain type of anti-depressant called selective serotonin reuptake Inhibitors or ssris  have received a lot of attention lately serotonin is a neurotransmitter and we'll visit it in more  detail in a minute but ssris are a therapeutic drug that targets the serotoni

n reuptake  transporter so though normally reuptake is very fast like immediately after releasing a  neurotransmitter an SSRI will slow the reuptake of Serotonin by blocking the transporter and this  inhibits the transporter's ability ability to draw serotonin out of the synaptic CFT and back into  the Press synaptic button the idea is that the longer serotonin can linger in the synaptic CFT  the more often it can stimulate the post synaptic neuron though to be clear we're still not super  sure

why ssris work and indeed in 60 to 70% of people with moderate to severe depression who try  ssris it will effectively help regulate their mood regardless hopefully you're getting a clear idea  of what's happening at the synaptic CFT after the neurotransmitter has been released the second way  neurotransmitters are cleaned up from the synaptic C is enzymatic degradation and that is when enzyme  activity breaks down the neurotransmitter into its component parts that can either be recycled  or dif

fused away from the synaptic Clift the enzyme responsible for degradation is going to  be particular to the neurotransmitter an example of this process occurs when the neurotransmitter  aceta Coline is released it is cleaned up by both enzymatic degradation and transporter molecules  the enzyme acetylesterase breaks down acetyl choline into choline and acetate molecules the  choline is drawn back into the praed button by the transporter molecule and recycle to make new  acetycholine I'm not 100%

sure what happens to the acetate I think it either diffuses away  or make it gobbled up by other non-neuronal cells and then the third mechanism of synaptic  Clift cleanup is diffusion diffusion is when the neurotransmitter floats away from the Clift into  the Great extracellular Space like a bunch of George cloony in the film Gravity except without  the untethering drama it appears this happens at just about every synaptic Junction there will be  some diffusion of neurotransmitters even if the

primary mechanism is reuptake or enzymatic  degradation so let's look at some of the different neurotransmitters and what they can do  and how they're cleaned up from the synaptic CFT as mentioned the two primary neurotransmitters  responsible for excitation and inhibition of signals are glutamate and gappa glutamate is  the primary excitatory neurotransmitter in the central nervous system so brain and spinal  cord and its main gig is to help move signals along from cell to cell until whatever

action  needs to happen happens if enough glutamate is released to the post synaptic neuron at the many  dendritic ends and spines if we use our example of the neuron the abundance of excitation ensures  the summation of inputs will total an excitatory synaptic potential which as we know already  increases the likelihood of propagating the signal onto the next neuron glutamate is also  active in learning and memory processes it may also be involved in the sleep wake cycle I think  that's been a

established in Mouse models but I'm not sure about humans glutamate can also be used  as fuel when ATP is low an interesting study by fent and colleagues intentionally inhibited the  glucose synthesis in neuronal mitochondria and found that the mitochondria instantly switched  to oxidizing glutamate to produce fuel this is helpful because too much glutamate can over  stimulate post synaptic responses and that could lead to increased toxicity called exitox toxicity  this results in cell death tha

t could lead to neurodegenerative conditions like ALS as well  as Strokes if neurons were redirected to consume excessive glutamate as a source of fuel that may  mitigate excitotoxicity levels not to worry though glutamate is usually removed from the synaptic  CFT by way of reuptake through Transporters in the Press synaptic membrane of special interest in the  health and wellness spheres are glutamate receptor channels so remember those are the receptor  plus ION channel units in the post synap

tic membrane that allow ions to enter the cell in  this case positively charged sodium ions that generate excitatory post synaptic potentials when  glutamate binds to that receptor part glutamate has four major types of receptors and one of these  glutamate receptors is called the nmda receptor and this receptor is special for many reasons it  plays an important role in learning and memory so you may have heard of it in that context  you may have also heard it mentioned during discussions of alc

ohol consumption and withdrawal  alcohol affects the transmission of glutamate by messing with the Gate of this particular nmda  receptor it's not able to stay open as long as it should which would lessen the excitatory effect  of this neurotransmitter and lower the firing rate of these neurons given the processes glutamate  is involved with tampering with its ability to do its J job interferes with memory learning  cognition and even some motor function so when you hear or read someone say that

alcohol is  an nmda receptor antagonist what they're really saying is that alcohol inhibits the function of  that particular glutamate receptor alcohol affects other cellular functions but I wanted to mention  the nmda receptor because it could be difficult to understand why this mechanism matters without  some context okay so moving on to Gaba it's the primary inhibitory neurotransmitter found in  the brain and spinal cord we didn't get into great detail on what happens at the post synaptic  m

embrane when an inhibitory neurotransmitter like Gaba binds to its receptor Channel other than to  briefly mention that depending on the channel it either lets potassium ions out or allows chloride  ions into the intracellular space to make it more negatively charged but again the summation of  the signal charge is what matters and if the total post synaptic potential is inhibitory it  won't propagate the signal any further and this is a good thing in many instances there's a reason  Gaba is the

primary and most abundant and widely distributed inhibitory neurotransmitter in the  brain well many reasons but first and foremost it stabilizes brain activity if neurons kept  firing all over the place it would be chaos in fact some researchers believe that disordered Gaba  production release and receptor binding underlies the onset of seizures and Gaba regulatory  function helps attenuate overactivity that would otherwise lead to anxiety agitation that  disrupts concentration sleep disturban

ces and even depression Gaba is removed from the synaptic cleft  by reuptake Transporters of note in health and wellness discussions Gaba also has several types  of of receptors at the post synaptic membrane but a particularly important one cleverly named Gaba a  is quite the target for numerous anxiolytic drugs which are anti-anxiety drugs one class you may  recognize is benzodiazepine they bind to this receptor to reduce anxiety and induce muscle  relaxation they've also been used to reduce se

izure activity and to remit Catatonia they do  this by unlocking Gaba a receptor to regulate any deficiencies in gabic function a cautionary note  about benzodiazepines prolonged use places the user at very high risk for developing dependency  or Worse an addiction to them I say prolonged but dependency can kick in if taken longer than 2  weeks dosage and duration must be monitored by a medical professional as does discontinuing use  it's not a drug you just stop taking the dosage needs to be ta

pered because full-blown benzo  withdrawal will make you wish you could crawl out of your own skin and that's partly due to its  persistent interaction with Gaba a receptors okay so I'll introduce a few more neurotransmitters and  some of them have roles in both the peripheral and central nervous systems how they are organized  in the central nervous system so brain and spinal cord can be quite complex so I think the best  way to give you context for now is to describe them as having their own s

pecific Pathways and  what I mean by Pathways is the trajectory a neural signal takes until it reaches its final  destination this trajectory can be neurons forming synaptic connections to other neurons  to propagate a signal along as many neurons as it takes until it synapses to neurons that kick  out different neurotransmitters it could also be just one set of axons projecting to a whole  other area of the brain I've heard the words Pathways and projections used interchangeably so  you may hea

r that too I believe it's referring to the same idea though perhaps projection is  referring more specifically to the axons and the directions they are projecting either way  it's referring to the root the neurons want the signal to travel in order to involve brain areas  needed to excite an action or inhibit an action but in the context of neurotransmitters their  Pathways begin where there is a cluster or an abundance of neurons that produce a particular  neurotransmitter and those neurons pro

ject to other areas of the brain and spinal cord in the  central nervous system glutamate and Gaba are widely distributed throughout the brain and spinal  cord you'll find them just about everywhere they are also involved in specific Pathways but these  next examples of neurotransmitters are not widely distributed in the central nervous system and  mainly have specific routs they take to excite or inhibit an action so first up is an excitatory  neurotransmitter called acetylcholine it's found bo

th in Central and peripheral nervous systems it  has a major role in the peripheral nervous system all of the neurons that excite your skeletal  muscles to make voluntary movements like my hands do so by releasing acetal choline all of  your skeletal muscles have col energic receptors go ahead and wiggle your fingers just now that  required acetal choline transmission to do just that in the central nervous system aceto choline  has specific Pathways and three that I'll mention are named accordin

g to the locations in the brain  where there are an abundance of acetylcholine releasing neurons we'll do a whole episode  on the brain very soon so not to worry if you don't recognize any of these labeled brain areas  just yet the first pathway begins in the dorsal lateral ponds and it is involved in REM sleep the  ponds is in the brain stem and dorsal means back think dorsal fin and lateral is side or furthest  from the midline of the brain so at the sides of the ponds and towards the back are

a bunch of  acetool energic neurons or also called coleric neurons and there are a few hypotheses as to where  they project to initiate the onset of REM sleep mostly neighboring neurons or possibly as far away  as the periaqueductal gray which is just above the ponds in the midbrain another cholinenergic  pathway begins in the basal forebrain basil means base so at the base of the forbrain  there is a constellation of coleric neurons and they project to the cerebral cortex to promote  perceptua

l learning the last colonic pathway I'll mention also begins in the basil forebrain but it  projects to the hippocampus and contributes to the formation of memories acetylcholine has loads  of other functions including regulating blood pressure and heart rate sexual desire motivation  and many other things I already used it as an example for how it's cleared from the synaptic  cleft but again it's broken down by the enzyme acetylcholinesterase into choline and acetate and  the choline is taken b

ack into the presynaptic button by reuptake Transporters and the acetate  George Clooney's it off into extracellular space probably okay the next neurotransmitter we'll  discuss is serotonin serotonin is an inhibitory transmitter interestingly even though most  conversations about serotonin involve the brain behavior and mood most serotonin is  produced outside of the central nervous system outside of mood and behavior serotonin helps  regulate vascular cardia respiratory metabolic gastrointesti

nal sexual urinary and reproductive  function it is busy in our bodies but even though so much of our serotonin is found outside of the  central nervous system serotonin neurons within it play an enormous role in modulating almost all  all human behavior and many neuros processes it modulates mood perception memory anger aggression  reward attention appetite sexuality and probably others outside of Behavioral effects it plays a  part in regulating other central nervous system processes like moto

r control sleep and circadian  rhythms even body temperature in the brain serotonergic neurons are mostly found in clusters  called the RAF nuclei and they live in sort of the middle or midline of the midbrain the ponds and  medulla which are all parts of the brain stem just above the spinal cord the clusters of serotonergic  neurons closest to the bottom of the brain stem project to the spinal cord the others project to  the rest of the brain like nearly everywhere in particular one part of the

rap cluster projects  to the cerebral cortex where it's involved with cognition mood impulse control as well as motor  function another part of the rafei cluster projects to the basil ganglia and ganglia is  another word for group so it projects to another group of brain structures in the center of the  brain that are responsible for movement learning emotional processing among other things another  part of the rafei cluster projects to the dentate gyrus which is part of the hippocampal structu

re  and is involved in memory formation there are other projections but as I said there's nary a  part of the brain where serotonin isn't projecting so hopefully that's enough to get a picture of  this incredibly diffuse and busy neurotransmitter I mentioned a few minutes ago that serotonin  is removed from the synaptic cleft by reuptake Transporters and a class of anti-depressant drugs  called selective serotonin reuptake Inhibitors or SSRIs block the reuptake transporter to keep  serotonin act

ive in the snaps for longer than normal of other interest in health and wellness  spheres the stimulant drug ecstasy also called methylenedioxymethamphetamine or MDMA massively  manipulates serotonin transmission among other neurotransmitters it seems to bind to serotonin  Transporters as well as other Transporters belonging to norepinephrine a neurotransmitter  will'll get to in a minute when MDMA binds to these Transporters it reverses the flow of  the these neurotransmitters and causes them t

o release back into the synaptic C but here's  the kicker it also prevents their re-uptake which massively increases their levels and duration  in the synaptic CFT this would have a lot of effects but it's possible the flood of Serotonin  contributes to the euphoric and hallucinogenic effect of MDMA before you get excited this kind  of massive neurotransmitter flooding also causes excitotoxicity which I've already mentioned  mentioned ravages your neurons and leads to cell death and cell death l

eads to damaged brain  structures and damaged brain structures leads to overall nervous system malfunction so it's not to  be taken flippantly or without medical monitoring preferably by a professional not your Uncle Jim  who used to make it in his basement and sold it as candy necklaces to kids at rapes there are  potential therapeutic uses of MDMA at the time of writing this episode there are drug trials  currently underway to determine its efficacy in treating post-traumatic stress disorder o

r PTSD  with so far very promising outcomes I've posted a phase 3 MDMA drug trial study in the references  section of the show notes if you're interested in learning more about it now that you've learned  a little bit about serotonin and re outtake Transporters you'll recognize what this paper  is talking about it's a pretty cool feeling when you can crack science-speak codes and academic  papers so I hope you at least give it a try okay okay so the next neurotransmitter is more than a  neurotra

nsmitter but we're going to mostly talk about its neurotransmitter and that is dopamine  I don't know how to feel about dopamine is it friend is it faux it's most definitely necessary  there's a number of dopaminergic Pathways Each of which have very different functions involving  multiple body systems it's involved in craving and reward motivation learning and approach Behavior  cognition motive function and prolactin regulation which is involved in vastly different mechanisms  from metabolism

to sexual satisfaction to immune function so all good things right but it's also  connected to addictive behaviors so the craving and pursuing of all those good things can become  uncontrollable so dopamine can be your best friend and also a bit of a sociopath or a micromanaging  narcissistic boss who if you enable will lock you into cycles that siphon every ounce of autonomy  and agency from your life but if you just let it think it's the best of all the boss molecules  running your body and oc

casionally affirm it's business Acumen it won't bleed your soul dry and  it may even let you keep a plant on your desk okay that's a a bit abstract but you'll get me if  you listen to the many many science Educators and wellness influencers talk about it I highly  recommend the book dopamine Nation by psychiatrist Dr Anna Lemke it's a really fascinating and  intimate dive into the many facets of dopamine's effects on our Behavior but most notably addiction  what I'm qualified to tell you is that

dopamine is both excitatory and inhibitory and it is both a  neurotransmitter and a neuromodulator it may also be a hormone it also makes nor I mean it's a bit  of an overachiever and possibly a control freak but we put up with it because let's be honest  chocolate thinking coordination and orgasms are worth it you're probably wondering how it can  be both inhibitory and excitatory it depends on the post synaptic receptor Channel dopamine  has several subtypes of receptors and some of them init

iate an influx of sodium ions that  make it excitatory and some initiate an efflux of potassium ions that make it inhibitory so what  about these many dopaminergic Pathways there are four major Pathways and many minor Pathways the  majors are mesolimbic mesocortical nigrostriatal and tuberoinfundibular Pathways we could talk  about each of them for days I mean everything in this episode we could talk about for days it  feels like I've been talking for days so thank you for sticking with me hang

in there a little  bit longer we're going to get into some of these major Pathways okay briefly the mesolimbic pathway  is the reward pathway and it begins with a group of dopaminergic neurons in the ventral tegmental  area also known as the VTA which is kind of near the upper front of the midbrain which is at the  top of the brain stem those neurons project to many areas of the limbic system which is deep  inside your brain above your brain stem most notably are projections that reach the nucle

us  accumbens amygdala and hippocampus the mesolimbic pathway is the pathway that motivates us to seek  pleasurable things like food sex achieving a long sought-after goal anything that feels rewarding  it's also the pathway that if not kept in check will kick you in the teeth not totally on its own  the mesocortical pathway lends a hand as well but it's mostly this pathway it's lovingly called the  reward pathway but it's also brutally known as the circuitry that with enough repetitive exposure

  to a reward organic or artificial can keep us compulsively craving and seeking more and more  of that reward for example every like share and retweet you receive on your socials begets the  craving and pursuing of more likes shares and retweets and oh my goodness when an internet  celebrity influencer or whatever unexpectely likes your comment on their account or better  responds to your comment favorably you feel amazing and what happens is you form an amazing  feeling Association to that rew

ard and once that Association has been formed it can continue to  have a strong influence on your drive to seek more of that reward for quite some time this crave  seek and act cycle can tether you to them without any assuredness of reciprocity but it's that  anticipation of reciprocity that they may like or comment or respond again that is what keeps you  seeking more of that reward and every time that reward is fulfilled the drive gets stronger the  Crave seek act cycle gets more and more repe

titive thus more and more addictive and some of these  influencers and most definitely these platforms Bank on you being in repetitive addictive crave  and pursue Cycles because that keeps you on these platforms for longer durations now I know all of  you probably have a very manageable relationship with social media but in the event that you  ever find yourself feeling pressure to be in a constant contact with anyone on your socials  whether that's external or internal pressure take a minute if

you're racing to comment on a post  in hopes it will be seen and then keep checking to see how many likes your comment has and if  that influencer or any Person of Interest has acknowledged you give it give it another minute  give it many minutes give it all the minutes instead of posting or checking put your device  down and go outside if it's safe for you to do so take a tour around your block say hi to a neighbor  or call a friend and tell them how wonderful they are exercise meditate read o

r listen to a book  like Dr ly's dopamine Nation interrupt the cycle you can actually kind of reset this pathway at  least in this context it doesn't mean you never check or post again but you get to control when  and why rather than letting when and why drive and control you now I've never met Dr Anna Lemke  I have no relationship with her I'm not trying to sell you books you can probably find dopamine  Nation at your local library what you may find helpful from her book is a dopamine reset pro

tocol  this is not a dopamine fast this is not a 24-hour reset this takes time she makes suggestions  backed by rigorous research on how to break free of crave seek and act Cycles including over  engagement with social media so that may be of some help to you it was enormous help to me okay  so that wasn't really at all brief but that was the mesolimic dopaminergic reward pathway next is  the mesocortical dopaminergic pathway this pathway also begins at the VTA again that's the ventral  t mental

area but it projects to the prefrontal cortex which is the top few millimeters of the  surface of your brain at the very front this area is where something called executive functions  live and that refers to cognitive functions and cognitive control but dopamine's role in these  processes has an excitatory effect on planning reason problem solving attentional control and  short-term memory dysregulation of this pathway is believed to contribute to ADHD addiction  and negative symptoms of schizo

phrenia okay so that one was brief next up the nigrostriatal  dopaminergic pathway this pathway begins with a group of dopamine neurons in the substantia  nigra pars compacta which is in the midbrain at the very top of your brain stem and those  project to Basil ganglia more particularly to the caudate nucleus and the putamen which are part  of the dorsal striatum it's a lot of words you may not know right now but we'll get to know them in a  future episodes you'll recall a serotonin pathway als

o leads to Basil ganglia and that this group of  brain structures is in the center of the brain and is responsible for movement learning emotional  processing and much more dopamine's effect on these structures is excitatory on GABAergic  neurons which then inhibit further striatal neural projections to influence voluntary movement  why activate an inhibitory response to movement well when this pathway is damaged voluntary  movement becomes uncontrollable or unstable symptoms of Parkinson's dise

ase emerge when the  nigral dopaminergic pathway is compromised from neurodegeneration in the substantia nigra so in  this pathway dopamine is working in cahoots with GABA to help you maintain control over voluntary  movements so you're not moving when you don't wish to okay so the last dopaminergic pathway I'll talk  about today is the tuberoinfundibular pathway this begins with dopamine neurons in the hypothalamus  which kind of sits at the top and in front of the brain stem and these dopamine

neurons project to  the pituitary gland which kind of drops underneath the hypothalamus and I say drops because there  really isn't a better way to describe what the pituitary gland looks like other than your brain's  tiny scrotum this gland connects the nervous system to the endocrine system and dopamine's  effect on this gland is to regulate secretion of hormones in particular prolactin prolactin  has a pretty vast CV from maternal processes to sex hormone regulation to Human Social bonding t

o  glucose regulation and appetite and Metabolism it has its fingers in a lot of pies dopamine's effect  on this pathway is actually inhibitory it's part of a negative feedback loot hello homeostasis and  a negative feedback loop that stops the secretion of prolactin again we have good reason to wish to  inhibit the release of something elevated levels of prolactin can cause prolactinemia which has  been correlated and by correlated it's not the same as causal but correlated with obesity insulin

  resistance fatty liver disease and infertility to name a few reasons why it should be regulated the  regulation of prolactin release is important and dopamine is the shut off part of that regulation  so those are some of the dopamine Pathways dopamine is removed from the synaptic Clift by  way of re-uptake Transporter and related to health and wellness spheres these Transporters are a  target for both prescription and recreational drugs much like the way ssris block serotonin  reuptake Transpo

rters the stimulant drug cocaine blocks dopamine Transporters preventing reuptake  and allowing it to accumulate and linger in the synaptic cleft for longer periods of time cocaine  is highly addictive going back to the reward pathway when the rewards of euphoria energy and  alertness is associated with the drug the drive to seek more cocaine to get that reward elevates  but diabolic Al the more exposure to cocaine someone has the more the brain desensitizes to  Natural reward stimuli and simult

aneously hypers sensitizes the neural circuitry responsible for  the stress response so even the slightest bit of stress can drive cocaine users to seek out more  cocaine and it doesn't stop there repeated cocaine use increases one's tolerance to it so you can  see where this is going more use at higher and higher doses so you can get trapped in the cycle  of rising cocaine use frequency and dose which plummets coping capacity to the slightest stress  which leads to increased frequency and dose

and it gets worse repeated high doses of cocaine leads  to developing sensitivity to its toxicity effects which means the more someone uses repeatedly the  less is needed to launch them into anxiety Panic convulsions paranoia potentially even psychosis  from there we're looking at brain damage and loads of other organ damage increased risk for stroke  brain bleed cognitive deterioration heart ruptures movement disorders it's really an unending list of  all the ways cocaine can break down someone

's body yet keep them just alive enough to thoroughly  experience their own deterioration if I didn't articulate this well enough earlier please don't  mess with dopamine let it do what it's supposed to do but do your best to not overindulge it so  the last neurotransmitter I'll mention today is norepinephrine also known as noradrenaline it  is both a neurotransmitter and a hormone I've heard that it's called neuro adrenaline when  we're referring to it as a hormone but I've also read the opposi

te so I'll just refer to it as  norepinephrine it is found in both central nervous system and the peripheral nervous system in the  peripheral nervous system it is a major player in the fight or flight response for more on that see  episode two as neurotransmitters in the central nervous system norepinephrine has two Pathways  that project to nearly every region of the brain one pathway begins with a group of neurons in the  locus coeruleus or Locus (k)oeruleus either way it's a fabulous name fo

r anything and sounds  like a planetary system somewhere in the Star Wars universe so the locus coeruleus is located  in the dorsal ponds so the back of the middle of the brain stem the other group is in the ventral  ponds and medulla these neurons project to all over the forebrain which is the whole top of your  brain including the cortex Thalamus and limbic system the lyic system includes the hypothalamus  hippocampus and amygdala they also project to other areas of the brain stem plus cerebel

lum  and spinal cord so pretty much everywhere norepinephrine has an excitatory effect on these  areas and its main gig is to increase attention alertness or vigilance to environmental events  it also plays a regulatory role in blood pressure and has roles in memory mood and sleep wake Cycles  interestingly norepinephrine is made from dopamine in the terminal button vesicles it is removed from  the synaptic cleft by reuptake transporter and is either degraded by enzymes or restored in vesicles 

of Health and Wellness interest norepinephrine is a key player in sleep regulation in that it  promotes waking and is highly active during wakefulness if you're on social media you probably  can't scroll 1 minute without coming across posts telling you that low solar angle sun exposure  in the morning and evening will help regulate your circadian rhythms well norepinephrine  may play a significant role in this Dynamic an older study by Gonzalez and Aston Jones found  that timing of light exposur

e is a catalyst in norepinephrine's role in sleep wake cycles as it  appears to contribute to the maintenance integrity and function of norepinephrine projections from  the locus coeruleus and robust Locus coeruleus projections and train circadian rhythms by  increasing wakefulness and inhibiting sleep during active periods of the day other notable  health and wellness considerations involve norepinephrine dysregulation when norepinephrine  transmission is compromised the downstream effects are

implicated in the development and progression  of Alzheimer's disease Parkinson's disease ADHD schizophrenia and depression so let's recap the  different neurotransmitters what they do and how they're removed from the synaptic cleft again  the synaptic cleft is a significant Target for both prescription and recreational drugs so if you  skip directly to this recap and wish to learn more about that I do give a few examples of which  drugs affect which neurotransmitter synapses in the previous man

y minutes so you may wish  should go back and listen to that okay so recap the two primary neurotransmitters responsible  for excitation and inhibition are glutamate and GABA glutamate's main gig is to help move  signals along from cell to cell until whatever action needs to happen happens it is also active  in learning and memory processes and it may also be involved in the sleep wake cycle glutamate  is usually removed from the synaptic cleft by way of reuptake Transporters GABA's main  job is

to to stabilize brain activity and help attenuate overactivity that would otherwise  lead to anxiety agitation sleep disturbances and depression among many other things GABA is removed  from the synaptic left by reuptake Transporters acetylcholine is involved in REM sleep perceptual  learning and contributes to the formation of memories it's also involved in regulating blood  pressure and heart rate and sexual desire and motivation and many other things it's cleared  from the synaptic cleft by

enzyme degradation and reuptake serotonin modulates almost all human  behavior and many neuropychological processes including cognition mood impulse control  learning emotional processing and memory formation it also plays a part in regulating  motor control sleep and circadian rhythms even body temperature serotonin is removed from the  synaptic CFT by reuptake transporters dopamine is implicated in a number of different functions  including craving reward motivation learning and approach Behav

ior cognition motor function and  prolactin regulation which is involved in vastly different mechanisms from metabolism to social  satisfaction to immune function dopamine is also a major player in addictive behavior it is removed  from the synaptic CFT by reuptake Transporters now norepinephrine's main roles include increasing  attention alertness or vigilance to environmental events memory mood and the sleep wake cycle it  also plays a regulatory role in blood pressure it is removed from the s

ynaptic left by reuptake  transporter and is either degraded by enzymes or restored in vesicles okay moving on I think at  this juncture it's important to gently remind everyone that none of these chemicals work  independently of each other in a siloed manner serotonin is isn't solely responsible for mood  dopamine isn't solely responsible for motivation neurotransmitters work in conjunction with each  other and with other body chemistry like hormones I've tried to simplify neuronal physiology a

nd the  neurotransmission process to give you a picture of what the neuron does and why but to be clear  intentionally increasing the levels of any one neurotransmitter won't necessarily increase the  action you're hoping for or if it does does you may not be fully clear about the demands you're  putting on other neural systems to compensate for that shift in homeostasis and I hope I've  also made it clear that messing with your brain chemistry without medical supervision could have  pretty disa

strous consequences I also want to clarify the difference between a neurotransmitter  and a neuromodulator I didn't really get into specifics of neuromodulation partly because they  don't behave the same way as neurotransmitters do and though some neurotransmitters can also  act as neuromodulators not all neuromodulators are neurotransmitter chemicals some are also  peptide hormones in a nutshell neuromodulators are released from a pre synaptic button in  a voluminous and diffuse manner to alter

the synaptic strength of multiple neurons and control  the amount of neurotransmitter released by these neurons while neurotransmitters create a  rapid effect on the post synaptic neuron and their action terminates in the synapse  immediately neuromodulators take their time and can produce either a short-term or long-term  excitatory or inhibitory effect ultimately they add a level of flexibility and adaptability  to neural circuitry some neuromodulators that are also neurotransmitters are acet

ylcholine  serotonin dopamine and norepinephrine and some of the effects on the body behavior that  I mentioned these chemicals produce may also be due to modulation rather than strictly  transmission okay we are nearing the end of this colossal episode but I didn't want to end without  going over some of the different types of neurons that you may hear mentioned in health and wellness  discussions so structurally neurons are classified as multi-polar like our example and that is common  in most

vertebrae animals unipolar is most common in invertebr organisms bipolar are found in most  sensory tissue and pseudo poolar is a version of bipolar neurons that that sense touch and pain  functionally neurons are classified as Sensory neurons which collect information from sensory  organs like eyes skin ears tongue and send it to the central nervous system for processing we have  motor neurons which carry signals from the brain and spinal cord to muscles to act in response to  sensory informat

ion and we have interneurons which connect some neurons to other neurons these are  very broad classifications and just about every neuron falls into one of them but as I said at  the very beginning of this Opus is that neurons are Fantastical cells Golgi and Ramoni Y Cajal  gave us a glimpse into their unique and wildly intricate morphology it seems almost a shame to  reduce them to such broad categories thankfully there are more particular names given to neurons  based on their structure and s

ome of those are the following purkinje and pyramidal cells which have  a Soma shaped somewhat conical or pyramid like there are basket cells which have loads of axonal  branches that surround the postsynaptic Soma there are stellate cells which are my personal  favorite their dendrites Branch out into star-like formations a little bit like the jazz hands of  neurons there are lots of others if you want to explore the many different kinds of neurons there  is a fantastic website with a searchabl

e gallery of digital renderings of so many different neurons  I'll post a link in the show notes the website is called neuromorpho.org and you can Browse by cell  type at the time of writing this episode they have 242,462 digital images of neurons cataloged  now there is one type of neuron I have not yet mentioned and those are mirror neurons it's a bit  of a stingy subject mainly because interpretations of how they function in humans have been somewhat  divided what I can tell you is that in hu

mans they appear to be found in the prefrontal cortex the  premotor area and possibly a few other neighboring areas in terms of physiological function mirror  neurons activate in equal measure whether we witness someone perform an action or we ourselves  perform the same action for example I see you pick up a mug my mirror neurons fire as though I  picked up the mug even though I did not perform that action I believe it's even possible that if  we were in total darkness and I heard you pick up t

he mug my mirror neurons would fire as though I  picked up the mug they are incredibly fascinating where it gets muddy and somewhat controversial  is to what extent mirror neurons are involved in higher cognitive processes in humans some have  interpreted that motor action mirroring could be a telepapathic like understanding of someone  else's actions this led to the hypothesis that mirror neurons enable us to predict and understand  another's mental state mirror neurons were lotted as cells tha

t read minds and may even contribute  to empathy a number of branches of social sciences have leapt at this hypothesis and even developed  psychotherapeutic modalities based on it there is still much debate as to whether there is enough  evidence to support whether or not mirror neurons actually make it possible for humans to infer the  intentions or mental States underlying another's actions one very clingy argument is that most  humans aren't clear of their own intentions or mental States unde

rlying their behavior or  actions so how could someone observing our Behavior understand what isn't clear in our own  minds there are many other arguments from both sides of the Divide but it seems the Neuroscience  Community are most mostly in agreement that based on current empirical evidence human mirror neurons  are involved in lower level visual processing of motor actions but there's not yet enough evidence  to support that they are involved in higher level cognitive processing that leads

to inferring  the mental States underlying the action but I'll leave you with an interesting and recent  study looking at possible mirror neurons and mouse aggression the gist is that certain neurons  in the mouse hypothalamus Act activate both when mice are fighting as well as when they're just  watching other mice fighting further to this their activation May trigger aggressive action and even  encode who wins the fight but again these neurons were in the hypothalamus not the prefrontal cortex

  they were also in mice and not in humans and the authors acknowledged that these neurons could  be part of a larger system of neurons in the hypothalamus which is a great reminder that  in humans any one Behavior or action is not the result of one group of neurons acting in a  siloed manner I have no strong opinions about mirror neurons and I'd like to try to keep  a curious and open mind toward anything we don't yet fully understand but if you have strong  opinions about miror neurons please

don't slash my tires but do let us know your thoughts in  the comments below remember to be kind people who have been studying mirror neurons for 30 years  still don't have all the answers okay so that's it for this week I'm starting to lose my voice but  thank you so much for hanging in there this was a lot of information and I hope at least some  of it was helpful your homework for this week should you wish to further your understanding of  The Magnificent neuron is to explore the work of neur

oscientists neurobiologists neurophysiologists  and the like who study the many functions Pathways networks morphology and physiology of neurons  here are a few to get you started first up is Dr Dani Bassett I'm not sure where to even begin  with introducing Dr Bassett to you because their research interests are so expansive and diverse  yet deeply and intrinsically tied to one another I should mention first that they are a professor of  bioengineering electrical and systems engineering physics

and astronomy neurology and Psychiatry  at the University of Pennsylvania that should give you some clue as to the range of Dr  Bassett's academic interests and Pursuits among the multitude of awards they have received  they were the youngest person to be awarded the prestigious MacArthur fellow genius Grant what  Dr Bassett is probably most well known for is their ability to connect systems engineering with  Neuroscience to identify underlying mechanisms of cognition and disease in human brain

networks  I am an absolute awe of the range and Genius of Dr Bassett's work I'll post a study from their  lab in the show notes it involves white matter development in adolescence white matter refers  to myelinated axons which relates very much to this episode it's one of at least 300 published  academic papers Dr bassett has co-authored also of note Dr bassett co-authored a book with their  twin brother Perry Zern called curious minds the power of connection I haven't read it yet but it's  on i

ts way to me and I'm really looking forward to reading it next is Dr Yasmin Hurd Dr Hurd is the  director of the addiction Institute at Mount Sinai the Ward-Coleman Chair of Translational  Neuroscience and Professor of Psychiatry Neuroscience and Pharmacological Sciences at The  Icahn School of Medicine Dr Hurd's lab studies addiction through genetics cell and molecular  biology and psychology among many other lenses her research repertoire is vast and includes risk  factors of addiction and the

effects of drugs of abuse on neural substrates in particular Dr Hurd  has made incredible contributions to furthering our understanding of cannabis on the Adolescent  and young adult developing brain I've posted a paper from her lab in the show notes it's a  systematic review which is the consolidation of many related studies and it's titled neural  underpinnings of social stress in substance use disorders you'll recognize many of the biological  and physiological Concepts in this paper if you'

ve been following this series from the beginning  including a thorough explanation of the negative feedback loop in the stress response the impact  of chronic stress on dendrites the impact of stress and drugs of abuse on the dopaminergic  reward pathway and so much more it beautifully articulates and expands on many of the things  you've been learning from this series and loads of brain areas and nervous system functions we  haven't even discussed yet but I highly recommend giving it a read and

maybe even keep going back  to it as we get further along in this series and see how much more you understand as we go if  this is unfamiliar territory for you next is Dr Diana Bautista Dr Bautista is a Howard Hughes  investigator and a professor of Cell Biology development and Physiology at the University of  California Berkeley neurobiology Department one of Dr Bautista's research interests is the somata  sensory cortex and its role in acute and chronic pain the paper I posted in the show not

es from Dr  Batista's lab is titled the cellular and molecular mechanisms of pain among the many biological  and physiological aspects of pain this paper discusses unmyelinated neurons called sea fibers  and their involvement in slow pain and touch which we briefly looked at in this episode lastly we  have Dr Kafui Dzirasa Who is a multi-award-winning professor of Psychiatry Behavioral Sciences  neurobiology bioengineering and neurosurgery at Duke University Dr Dzirasa diverse research  interest

s range from what electrical patterns in the brain can tell us about coping mechanisms to  how machine learning can predict mental illness and to how genes associated with neuropsychiatric  risk interact with environmental stress and alter neural circuitry that underlies healthy emotional  and cognitive function I've posted an older study he authored in the show notes and it's about  dopaminergic control of sleep wake States and its relation to psychosis in Parkinson's disease it's  brimming wit

h terminology from today's episode again also if you scroll to the end of the show  notes or possibly pinned in the comments you'll find a list of papers and books I sourced to write  this episode so you may find something of interest there as well finally I will leave you with this  fabulous quote from Santiago Ramon Y Cajal where he states that "neurons are mysterious butterflies  of the soul the beating of whose wings might one day who knows reveal the secrets of mental  life." okay lovelies

thank you for being here again please check out the stem organizations in  the show notes and support them or others in any way that you are able I have no relationship  with these organizations I'm just a fan of the work they're doing and I hope that you will be  too if you like this episode please click like And subscribe and the notification Bell if you  haven't already please share it with your friends neighbors and family and anyone you think would  benefit from understanding their body a l

ittle better you've been a dream for staying the whole  way to the end until next time take care out there [Music] so excited I love this episode okay okay I'm ready I'm gonna pass out all right okay [Music]