Neurons, Synapses, and Signaling

Question 1

Example of organism that utilizes nervous system to get their prey: Tropic Cone Snail

Answer 1

Carnivorous organism

Question 2

How does tropic cone snail use the nervous system to acquire their prey?

Answer 2

the mechanism they use to acquire their prey is through the release of toxic molecules; these toxic molecules disrupt (mess up) the prey’s nervous system, which is how the snail utilizes the nervous system

Question 3

What does the toxic molecules do?

Answer 3

The toxic molecules, upon injection, will result in the prey responding with paralysis and death

Question 4

What are the two different pathophysiology (ways) in which snail can cause death through toxic molecules?

Answer 4

1. Respiratory toxicity
   - the intercostal muscles and diaphragm depend on nervous system, so if we are messing with the neuromuscular pathway within respiration, can cause breathing to stop –> death
2. Cardiovascular toxicity
   - heart has autorythmicity and communication in terms of facilitating muscle contractions via nervous system, if that is messed up, prey will no longer be viable

Question 5

Can both toxic effects happen at once?

Answer 5

Yes, both respiratory and cardiovascular toxicity can occur separately or together

Question 6

What is dependent on which toxic effect happens (either one or both happening)?

Answer 6

The outcome of the effect of toxicity is dependent on the peptides in the venom on the snail, and the specific types of neuromuscular pathway they interfere with; can be a cocktail (a bunch) of diff peptides that mess up signal transduction pathways that are essential in the body

Question 7

How does a neuron transmit information?

Answer 7

A neuron receives information, which passes along the axons

• at the end of the axon is the synapses, and the synopses has a synaptic terminal where info (neurotransmitters) come out from
• Neurotransmitters, which are signaling molecules, is what gets transferred from the neuron it’s coming out from to the other neuron or other cell it’s going into

Question 8

Overview of the nervous system:

Answer 8

next slide

Question 9

What are the two different anatomical divisions in the nervous system?

Answer 9

Central Nervous System (CNS) and Peripheral Nervous System (PNS)

Question 10

What is in the CNS?

Answer 10

The brain, which is enclosed and protected by cranium and spinal cord, which is enclosed and protected by vertebral column

Question 11

What is in PNS?

Answer 11

Everything else

Question 12

What is the

Question 13

More specifically, which two categories does PNS get broken into?

Answer 13

Sensory Division and Motor Division

Question 14

What does sensory division do?

Answer 14

carries signals from diff types of receptors from sense organs and sensory nerve endings, and carries that information to CNS; sensing something, and sends that info towards the CNS

Question 15

Within sensory division (which is one of the two division in PNS), what are the subdivisions within it

Answer 15

In sensory division there is visceral sensory division and somatic sensory division

• Visceral sensory division: consists of receptors in viscera, thoracic, and abdominal cavities; which is receptors in heart and lungs
• Somatic sensory division: receptors in skin, muscle, bones and joints

both scenarios still have signals from receptors in those locations go towards the CNS, for the CNS to process what it will do will that info to respond

Question 16

Other division in PNS: Motor Division, what does motor division do?

Answer 16

carries signals towards muscle cells so that it can carry out the body’s responses

Question 17

Within motor division (which is other part of PNS) what are two subdivisions and what do they do?

Answer 17

In motor division, there is somatic motor division and visceral motor division

Somatic motor division: send signals to skeletal muscles, like in arm and legs, will lead to muscle contractions, things you can control voluntarily (voluntary muscle)

Visceral motor division: carries signals to glands, cardiac muscles, smooth muscles (places that lack voluntary control) can break it down even further into:

• sympathetic division: fight or flight (accelerated heart rate, increased respiration, and decrease non essential things such as digestion
• parasympathetic division: calming side, reduction of heart beat, back to providing emphases to processes such as digestion

Question 18

Note: Nervous system in general is about sensing something, processing that info, and then commanding the body to lead to downstream response; whether talking about muscle cells or glands cells

Question 19

Module 1 all about form and function

Answer 19

Neuron reflects form and function with its shape and organization, continue to think about it throughout chapter

Question 20

What do neurons do?

Answer 20

Neurons are all about receiving, conducting, and transmitting signals in that order
-receives a signal, conducts that info throughout it’s body, and then will transmit the signal, leading to some type of effect or outcome

Question 21

What are the properties of neurons?

Answer 21

Property: effective communication
Property: extremely excitable; will elicit a response
Property: longevity
-can function optimally for a lifetime as long as there’s adequate nutrition available
Property: amitotic
-lose ability to divide, cannot be replaced if they are destroyed so they stay in G0 on cell cycle, in quiescent phase
-BUT some neurons can be replenished in specific parts of the brain that have an adult stem cell population
Property: High metabolic Rate
-have high metabolic rate, so need a lot of oxygen and glucose for ATP production
-So neurons are highly sensitive of being deprived of oxygen for a few mins bc they are constantly doing work and need energy to go through the process of communication

Question 22

What is the Neuron Structure?

Answer 22

Soma/Cell Body:

• control center
• similar to other cells; has the organelles
• has extensive rough ER; helps with lots of protein synthesis bc of the presence of lysosomes
• Lack centrioles: without centrioles, can’t divide, so neurons don’t have necessary components for cell division

Dendrites:

• extension of the body
• short branching extensions are input regions
• provides a ton of surface area in order to help receive signals, like from other neurons
• can take those messages/signals and convey them toward the soma

Axon hillock:

• end of soma/cell body
• gives rise to axon
• specialized for fast conduction of nerve signals to points that are distal (far) from the soma

Axon:

• has cytoplasm (axoplasm) and membrane (axolemma)
• at the distal end of exon from presynaptic cell, we will see a bunch of branching
• there will be synaptic terminals

Synaptic terminals:

• bulbuls region at the end
• where neurotransmitters come out into the synapse

Synapse:

• small space between presynaptic cell and postsynaptic cell
• as synapse, small expansive space where neurotransmitters will migrate from presynaptic cell to post synaptic cell

Neurotransmitters are signaling molecules and is how presynaptic and postsynaptic cells communicate via the presynaptic
synaptic terminal releasing neurotransmitters to the dendrites in postsynaptic cell

Question 23

What is seen in an nerve tissue?

Answer 23

Neurons and their supporting cells called neuroglia

Question 24

Which are more seen in nerve tissue?

Answer 24

Neuroglia are seen wayyyy more than neurons

Question 25

What are neuroglia?

Answer 25

Neuroglia look like tiny punctate staining (see in tissue sample) tiny spots that play a supporting role for neurons

Question 26

How do they help support neurons

Answer 26

Neuroglia cells provide support and protection for the neurons

• able to hold neurons in place, which is important to prevent neurons from interacting with each other inappropriately
• this helps to ensure that interaction takes place at specific location where signal transmission should occur; allows for conduction pathways
• can also provide nourishment for nerve cells to maintain homeostasis they need

Question 27

What are the different types of neuroglia?

Answer 27

There are 6 types of neuroglia (again neuroglia are supporting cells for neurons found in nerve tissue

• there are 4 in CNS
• 2 in PNS

Question 28

What are the 4 in the central nervous system and what do they do?

Answer 28

1. Astrocytes
   - star shaped
   - will have perivascular feet
   - perivascular feet will contact blood capillaries and can help stimulate them to form
   - perivascular feet also form a tight protective layer known as blood brain barrier
   - blood brain barrier strictly regulates what can get from the bloodstream into the tissue fluid of the brain
   - since the astrocytes are so closely compacted together due to the perivascular feet of the astrocytes, this means that if anything wants to go into tissue fluid of brain, needs to go THROUGH the cells
   - this means only small molecules can go through; such as water, glucose, oxygen, but also alcohol, caffeine, and nicotine
   - this blood barrier is good as you can’t really replenish neurons, as most of them are amitotic, so it prevents pathogens from entering that would damage tissues and its components
   - but bad for chemo as chemotherapy drugs won’t fit through barrier, making brain tumors hard to deal with
   - they monitor neuron activity, which can lead to stimulation of dilation and construction of blood vessels, which allows blood regulation in brain tissue based on the neurons need for oxygen and nutrients from blood
   - can regulate composition of blood tissue from reaching high levels by taking up neurotransmitters and potassium ions that are released by neurons, so regulating signal transduction pathways from occurring if its too much
   - when neurons are damaged in CNS, astrocytes will form scar tissue and fill that space that had those neurons, which is why nerve regenerating not effective as the scarring response astrocytes do (if they can even regenerate at all)

Ependymal cells:

• ciliated cells
• found lining central cavities of brain and spinal cord
• forms permeable barrier btwn the cerebral spinal fluid that fills those spaces
• CSF helps cushion brain and spinal cord, and chemical stability
• ependymal cells are supporting cells for CSF by forming permeable barrier btwn CSF and and brain and spinal cord, and also the cilia movement of ependymal cells helps circulate the CSF

Oligodendrocytes:

• insulate nerve fibers with covering called myelin sheath
• myelination important to propagating signals along a nerve fiber (axon)
• provides structural framework (for the axons I believe)

Microglia:

• small macrophages develop from monocytes
• wander through CNS and put out projections to sense for anything that doesn’t belong to go through process of phagocytosis and inject them
• where we see increase in microglia is where this is prob injury, as it shows where damage is
• presence is important bc the cells of immune system cells have limited access to CNS, so reliance of microglia is important to achieve phagocytosis when there’s an invader to prevent damage (and if there’s a lot of microglia, prob means there’s damage, so can better locate injury in the brain/spinal cord)

Question 29

Neuroglia found in PNS:

Answer 29

1. Satellite Cells
   - surround the somas within the peripheral nervous system
   - help regulate chemical environment of the neurons
   - regulation of gases, nutrients, neurotransmitters
2. Schwann Cells:
   - surround nerve fibers in the peripheral nervous system and form a myelin sheath around thicker nerve fibers to insulate them
   - functional similar to oligodendrocytes (CNS neuroglia)
   - integral to the regeneration of damaged peripheral nerve fibers bc it is achievable to repair post injury within the peripheral system as compared to CNS bc of the scar tissue that forms bc of astrocytes in the CNS (remember this is talking about repair NOT making new ones as only a few neurons in CNS have stem cells, others are all amitotic)
   - So in PNS there is actual repair processes that can occur, and Schwann cells help surround nerve fibers and form a myelin sheath

Question 30

What is the basics of information processing?

Answer 30

Sensory Input:

• nervous system uses sensory receptors to monitor changes occurring both inside and outside the body
• the neurons associated with sensory input are afferent, meaning they will conduct signals towards the CNS with what they find

Integration:

• Nervous system process interprets that sensory input and decides what should be done in that moment
• lies entirely in CNS, and will serve as interconnection btwn sensory input and motor output

Motor output:

• nervous system activates effector organs/motor neurons
• motor neurons are efferent, meaning they will conduct signal away from CNS, to PNS
• Muscles or glands that will conduct a response is known as motor output

Question 31

What is the structural diversity of the different neurons in the process of information processing?

Answer 31

Sensory nuerons:
-have a very long axon which makes sense as it has to travel to the CNS from where they are to gather these signals from changing in and out of body (long distance travel)

Interneuron: these are CNS neurons that have to process information and SEND it to motor neuron in PNS, so its axons have extensive branching for a lot of synaptic terminals to release the neurotransmitters (signals) to the motor neuron

Motor neuron:
-these are PNS neurons that receive signals from the CNS interneurons to do what the neurotransmitter signal says, so they have large and extensive dendrites to receive that signal

Question 32

Module 2: Resting Potential

Question 33

Is the body electrically neutral or charged?

Answer 33

body overall is electrically neutral BUT there are areas in our body that are + charged and areas that are - charged

• opposite charges have a level of attraction toward one another so keeping them apart requires work and energy to be put in in the form of potential energy
• we can then harness the potential energy to do something, thus utilizing the charge seperation while still overall having an electrically neutral body

Question 34

What is a voltage?

Answer 34

A voltage is established through a difference in electrical charge seen across a plasma membrane

• based on specific voltage differential seen across bilayer and not just overall ions outside the cell and inside the cell, we are looking at discrete regions
• bc of this, the neuron has a level of excitability when there are deviations of this voltage across plasma membrane (the charge on one side is increased or decreased than normal, throwing off the voltage as voltage is the difference btwn the charges on both sides)

Question 35

What are the two terms we can use for neurons when it comes to voltage?

Answer 35

Resting potential and active potential

Question 36

What is resting potential?

Answer 36

Resting potential is a neuron at rest

• not sending signals bc neurons focus on communication and communication occurs through the contuined receive transfer of those signals
• but a neuron at rest is not going through that process, as its voltage is stable and there is no deviations between the charges of ions across the bilayer of plasma membrane of ion

Question 37

What is action potential?

Answer 37

When the right conditions occur, then action potential can be elicited

• the way a neuron can elicit an action potential is through changing the membrane potential, changing the voltage
• level of sensitivity to the voltage found at membrane (differences of charge) so that we can use that sensitivity for a neuron to elicit a signal based on changes that occur across a bilayer

Question 38

What ion concentrations impact the resting potential of a mammalian neuron?

Answer 38

The ions that are going to be critical for establishing the resting potential are:

• Potassium ions
• Sodium ions
• Chloride Ions
• Large Anions (A-), such as proteins inside the cell
• potassium and sodium will be discussed more
• chloride ions are less involved in establishing resting membrane potential
• presence of large anions play a role in resting potential based on electrostatic attraction
• for potassium ions: way more inside cell than outside
• for sodium ions: way more outside cell than inside
• for chloride: way more outside cell than in
• large anions: only inside cell

Question 39

What are the properties to consider in the role of resting membrane potential?

Answer 39

Electrostatic attraction and idea of diffusion will help influence what the charge will be across the phospholipid bilayer (what the voltage will be)

Question 40

What is resting potential?

Answer 40

Resting potential is the membrane potential of a neuron that is not sending signals

• membrane potential is the separation of charge across the plasma membrane
• the voltage of resting potential is quantified as the measurement of potential energy based on separation of charges

So basically, there is a voltage which is a number that is the potential energy. This potential energy is based on the separation of charges. The separation of charges across a plasma membrane is the membrane potential. Thus, resting potential, is the membrane potential of a neuron that is not sending signals.

Question 41

What impacts resting potential?

Answer 41

The imbalance of sodium, and potassium cells in extracellular fluid vs. intracellular fluid

• for sodium ions, there are more ions on the extracellular fluid than intracellular fluid
• for potassium ions, there are more ions on intracellular fluid than extracellular fluid

Also, trapped anions inside the intracellular side only, such as proteins and RNA, can’t pass through plasma membrane (too big), but they serve a role to hold on to the opposite charge in the intracellular fluid and prevent it from diffusing down concentration gradient (prevents K+ from going out of cell bc K+ is attracted to the anion in the cell, more than diffusing out to balance the concentration)

Resting membrane potential is due to unequal distribution of components found on either side of phospholipid bilayer, due to K+ being a lot in intracellular membrane and Na+ being a lot in extracellular (even tho they diffuse down their gradients to the side that’s less, there is selective permeability of the membrane, so some ions pass more easily than others)

What also helps unequal distribution at resting potential is the sodium potassium pump
- 3 sodium ions into extracellular fluid (against the gradient)
- 2 potassium ions into intracellular fluid (against the gradient as its already in high concentration)
helps with unequal distributions as well and requires ATP

-All of these factors contribute to resting membrane potential, which is the differences in charges when there’s no signal, when neuron is at rest, that has a voltage, a number of its potential energy (bc its doing no work its PE)

Question 42

Resting Potential: showing imbalance of sodium and potassium ions through sodium potassium pump

Answer 42

Sodium Potassium Pump overview:

1. sodium potassium pump facing intracellular side where there is low concentration of Na+ and high concentration of K+. The pump has a high affinity for Na+, and thus 3 Na+ bind to the transmembrane protein (the pump)
2. When the pump is full with the 3 Na+’s, ATP is broken down and the phosphate attaches to the protein,
3. The phosphorylation event changes its shape to go from facing cytoplasm (intracellular) to facing extracellular
   - at this point the affinity for Na+ goes down for the protein pump and thus the 3 Na+’s go out into extracellular fluid (where this is already a high concentration)
4. The K’s from the extracellular fluid have a high affinity to the pump, and 2 K’s bind to the pump as its now facing the extracellular fluid
5. Once we have a fully occupied state, with 2 K+’s binding, we have hydrolysis of the phosphate group which removes phosphate from the protein pump, resulting in the protein to go back to its original state, which was facing the cytoplasmic side
6. In the cytoplasmic side, now there will be a decrease in affinity for K’s for the protein pump so it will be released in the intracellular side (where this is already a high K+ concentration)

In this process, we were able to use active transport via a protein pump to move 3 Na+’s out of the cell and 2 K+’s into the cell, so we have an unequal distribution of ions across our plasma membrane (with so much K+ inside and so much Na+ on the outside) which adds to the resting potential

Question 43

Resting Potential: showing inbalance of charges using Nersnt Equation and leaking channel

Answer 43

Nerst potential describes the relationship membrane potential and ion concentration
We generate a value for Nerst potential for each specific ion
In looking at the equation, the math doesn’t matter as much as the result we get
Result: the nernst potential for K+ is very negative while Na+ is positive
Bc the density of potassium leak channels found along the neuron compared to sodium is different
There are way more potassium leaked ion channels compared to sodium, the Nerst potential for K+ has a higher contribution towards what is considered the resting potential on the neuron which depending on the nehon in question could be -80 or -70
But it will never be exactly of -90 bc we have to account for the Na+ (+62)
Potassium (K+) exerts the greatest influence between the membrane and it is permeable to it
So K+ is more permeable to the membrane than the Na+, one of the factors that contributed to resting membrane potential
If you have K+ ions diffuse down its concentration gradient and heading out of the cell, it’s going to leave cytoplasmic anions and recall that those are things that are incapable to making their way out of cell, so stuck on inside
Exert an attractive force on the ions to stay on the inside
Once a balance is reached between the desire to diffuse down a gradient vs. the electrical attraction for what remains inside, we find that it leads to many more times of concentration of K+ in intracellular fluid as compared to extracellular fluid
When it comes to this equation, the numerator reflects the concentration of the ions seen on the outside
Denominator reflects the concentration of that particular ion seen on the inside
For the Na+ ions, the sodium ions way more concentrated on the outside, which would be the numerator here
Still capable of diffusing down its gradient but its less permeable and fewer of leak channels present, so small amount of trickling out that occurs
See you have a chamber
Inner and outer chamber
Not meant to reflect true conditions
Doing something in vitro to get an understanding of how these ions behave
Bc we see these differences in terms of the behavior of each of these particular ions, anything that’s going to modify or fluctuate the movement of these ions is going to have an impact on the voltage seen across that membrane

Question 44

Module 3: Action Potential

Answer 44

• action potential conducted by axons
• not just utilizing proteins that are responsible for resting potential (leak channels and sodium ion pump both contribute to K+ being high in the cell and low outside and Na+ being high outside cell and low inside, which creates difference in voltage = resting potential)
• ready to conduct a signal
• technique used to show us how we can record that resting potential, using micro electrode attached to neuron and that is attached to voltage recorde

Question 45

What is the protein that is regulated by fluctuations in membrane potential?

Answer 45

the protein that is regulated by the fluctuations in the membrane potential is the ion channels.

• they only open when there is a change in voltage aka change in membrane potential (as that is what a voltage is)
• when it is open, ions go down their concentration gradient

This is diff from leak channels and sodium potassium pump as that is open regardless and actually creates the voltage and membrane potential (so fluctuations with these will impact whether or not the ion channels are open!)

Question 46

What is a local disturbance?

Answer 46

A local disturbance is a change that is happening in a localized region of the neuron that leads to a type of response

An example of local disturbance is a graded potential.

Question 47

What are the two diff types of graded potentials?

Answer 47

A graded potential is when there is a change in polarization, this can either lead to depolarization or hyperpolarization

If graded potential is a depolarization event:
-then there is going to be a reduction in the magnitude (number) of the membrane potential
-this means there the difference we see on either side of the phospholipid bilayer lowers, which will raise the number of the membrane potential, changing it from its rest position
-Since the rest number is at -70, the depolarization even will be a stimulus that will reduce the magnitude of membrane potential and cause numeric value to increase of membrane potential (voltage)
How this happens: during a depolarization event, there is going to be increased movement of Na+ ions which will diffuse down its concentration gradient (to the inside of the cell)
-since membrane potential is outside of the cell/inside of the cell (not sure if there’s a membrane potential for both Na+ and K+ or the addition of both of them), regardless, increasing the Na+ inside the cell means there will be a lower difference seen of Na+ on either side, which raises the number

If graded potential is hyperpolarization even:

• if we’re at rest at -70 and have hyperpoloraization, we’re increasing the magnitude of the membrane potential, increasing the difference that is seen of change across a phospholipid bilayer, thus lowering the number of membrane potential
• How it works:
• hyperpolarization leads to a an increased permeability of K+ ions, and the K+ ions will travel down their concentration gradient into the extracellular side
• this results in further increase in the negative charge in the cytosol and makes their be more K+ in the outside and in the formula outside of cell/inside of cell of ions, the outside of cell will be higher, so it will result in a higher magnitude of membrane potential, which results in a lower number of membrane potential

Question 48

Can you have a variety of strengths in graded potentials?

Answer 48

Yes, there is a variety of strength of the stimulus

• local potentials get weaker as they spread from the sight of stimulation
• signals can start to dissipate if nothing is done with it
• graded potentials is reversible as when stimulus is removed, membrane voltage returns to resting (-70 = resting potential)

Question 49

Sum up of depolarization and hyperpolarization

Answer 49

Depolarization:
-there will be lowered magnitude of membrane potential –> which results in higher number of membrane potential
How it works: -membrane will be more permeable to Na+ ions, and will cause Na+ ions to go down their concentration gradient, resulting in them going inside the cell
-this will make the inside of the cell more positive and as the magnitude equation is (outside of cell vs. inside of cell), this will result in a lower magnitude, which raises the number of the membrane potential
(Na+ going into cell, magnitude of membrane potential going down, number of membrane potential goes up = depolarization

Hyperpolarization:
-there will be higher magnitude of membrane potential –> leads to lower membrane potential number
How it works:
membrane will become more permeable to K+, and thus K+ will go down its concentration gradient out of the cell into extracellular part
-this results in more negative inside of cell (in addition to anions, there are now less K+’s), and results in a higher magnitude for membrane potential as it is outside of the cell/inside of the cell
-this results in a lower number for membrane potential, below the resting potential

Question 50

Action Potential Intro- is graded potential = action potential?

Answer 50

NO! when graded potential, such a deporalization stimulus, is very strong and passes the threshold, which is -55 mV (so we would need depolarization as it increases the number of membrane potential, making it less negative, due to the decrease in magnitude of membrane potential as Na+ ions go from outside cell to inside and its outside/inside)
-this will result in an action potential and once it reaches the threshold this process will start

• eventually it will come down and repolarization will occur to head back towards resting
• there will be some overshooting where we go a little below resting potential when we come back down but then go to resting potential (-70 mV) again

Question 51

Going through diff steps of action potential:

Question 52

1. Resting State

Answer 52

• prior to dramatic depolarization event that yields action potential, we have resting state
• at resting state voltage gated channels CLOSED
• these are NOT the leak channels, that are always open and sodium potassium pump, that is always working as that is always on due to it being part of resting potential
• will work in any state
• these voltage gated channels are ion channels talked about in earlier card)

Question 53

2. Depolarization

Answer 53

Initial depolarization
Local potential that begins and as a result we have an open voltage gated sodium channel
In an open state
Sodium ions go down gradient → enter cytosol
Result in a reduction in magnitude bc we’re bringing + charges inside cell, decreasing the difference seen in phospholipid bilayer
In this portion, we don’t have both voltage gated sodium channels, just one
Start some movement which leads to semi gradual depolarization event

Question 54

3. Rising phase of action potential (reaching threshold that will result in many sodium ion channels opening an more sodium ions in the cell, which results in a larger (more positive) membrane potential

Answer 54

Distinction of depolarization we saw in 2 vs where we are at in 3 is that we have now reached threshold
Reached -55 mV, and voltage gated ion channels open up more quickly and all of them open for sodium in this scenario
Allow for even more ions into the cell and bring the membrane voltage towards a more positive integer
Positive feedback loop → it’s going to encourage more sodium channels downstream to open up as well
Allow for rapid rise in membrane voltage
It goes closer and closer to 0, getting away from - integers bc we’re moving more + ions into the cell
K+ ions are in a closed position here
Technically, K+ should be starting to open, but they do so much more slowly than the sodium channels

Question 55

4. Falling phase of the action potential
   Falling phase:
   Voltage gated sodium ion channels are inactivated (utilization of inactivation loop)
   This occurs when voltage passes 0 mV
   Results in refractory period where there can be no depolarization while the ion channels are inactivated
   A second action potential cannot be initiated at this current point
   We also have voltage gated K+ ion channels open, which allows for K+ to exit out the cell and go to outside of cell
   Leads to repolarization, as membrane voltage goes back towards a negative integer

Answer 55

Rapid depolarization once threshold is reached
Now we’ll start to fail
As voltage passes around 0 mV, sodium channels become inactivated
The inactivation loop is now in such a state that it is physically blocking the channel
NOT the same as closed confirmation state (where it flips around, that’s for sodium potassium pump)
For voltage ion pump, we have closed (at resting potential), open (at initial depolarization and once it hits threshold rapid depolarization where many sodium channels open) and inactivated (HERE at falling phase of action potential → once it hits 0 mV)
In the inactivation stage inactivation loop physically blocking the channel, so not possible for ions to go down the gradient at this point
We also notice that during this failing phase, have a reduction of sodium movement into the cell, and now we have K+ channels fully open, which will allow for K+ to exit out of the cell and go into the outside of cell
Going to lead to repolarization
Shift of the membrane voltage back towards a negative integer
Falling phase = repolarization
Also going to be refractory period: time in which action potential cannot be initiated
The refractory that is associated with this portion of action potential is considered absolute
It due to the temporary inactivation of the voltage gated sodium channels
Point that we essentially start this process through inactivation
Impossible for there to be any additional movement of sodium ion, therefore that will prevent for a depolarization to come right behind this one
We don’t want to have this constant depolarization one behind the other so this is good

Question 56

5. Undershoot (Na+ inactivation loop no longer blocking channel but now we have closed state of sodium channel, K+ still open which will result in more K+ leaving ion, and there’s no Na+ coming in so the cell will temporarily be more negative then it was during resting potential –> hyperpolarization
   (falling phase had repolarization (heading back towards negative integer) while undershoot has hyperpolarization (below resting potential)

Answer 56

Undershoot
No longer have inactivation loops blocking but our voltage gated ion channel is in a closed state
Both scenarios, sodium ions cant flow through, but now we are closed and not inactivated
K+ channel still in open confirmation
While it was way slower to open compared to sodium channel, it will stay open longer than sodium ions’
So, more K+ will leave the cell which will cause the cell to temporarily be more negative that it was at rest
Resting membrane potential = -70 mV
So this would be at -80 or -90
Results in negative overshoot = hyperpolarization
falling phase- had repolarization (heading back towards - integer)
Undershoot = hyperpolarization (went to far below resting potential
Our voltage gated sodium channel in closed confirmation
Refractory period which will last until hyperpolarization ends
Called the relative refractory periods
Refractory periods
At this point of the axon, we think about a refractory period taking place, but does not signifying whole axon going through this as it is a cascade

Question 57

Action Potential Sum up

Answer 57

Cyclical
After have hyperpolarization event eventually get back to rest
At rest everything (ion channels) is closed, including potassium channel as thats what helps it get back to rest
In order to get back to -70, still have leak channels, and sodium potassium pump that is responsible for maintaining that rest state
Help get out of hyperpolarized region
Action potential is different that local potential and graded potential
Stimulus → want to be able to maintain threshold (which is -50 mV)
All or nothing
Trend will look the saem o
Once we get to -50, the shoot up and then the falling and overshoot always occurs like this
Our ability to get there relies on 2, which is initial depolarization prior to reaching threshold
If 2 is enough to get to -50 mV, we will go through action potential
Can’t stop action potential once its begun, which makes it irreversible once it starts

Question 58

Refractory Periods
(Absolute refractory period- after the peak activation potential (rising of the action potential), there is a falling of the action potential in which K+ channels are open and K+ is coming out of cell, lowering the membrane potential, AND sodium channels are inactivated due to an inactivation loop
-At this point there can be NO second action potential as change in voltage cannot open the Na+ channels as they are in inactivated state, not closed one 

During overshoot (after replorization described above), the sodium channel will turn from inacitvated to closed (still not open, but it being closed means it has the opportunity to be open given the right circumstances)

• Since the K+ going out of cell has gone a little bit too far (cell too negative below resting period), for a second action potential to occur (as now it can potentially happen as we have Na+ closed not inactivated), it needs to be a VERY LARGE stimulus to get it to reach the threshold as now it is even below the resting potential
• if the stimulus can do that, a seocnd action potential can come after the first NOT in the absolute refractory period where Na+ ion channel is inactivated but in relative refractory period where Na+ channel is closed and can thus be open given right circumstances

Note: the larger stimulus may never happen, doesn’t have to happen and at that point, membrane potential goes back to resting potential and action potential can happen again from there

Answer 58

When voltage gated sodium ion channels inactivated (during peak of action potential), the membrane is in absolute refractory period
There can be absolutely no action potential that occurs during this time
That portion of the membrane is going to be unresponsive to another stimulus bc our sodium channels are inactivated rather than closed
Change in voltage cannot open the Na+ channels while they are in an inactivated state
As we go through action potential, and the membrane begins to repolarize, the inactivation gate is eventually released and the voltage gated sodium channels go to closed state
Now we have that undershoot; the time in which the voltage gated K+ channels are open, and there’s going to be brief relative refractory period
The membrane is hyperpolarized (hyper negative)
In theory, a new action potential can be generated but it requires a really large stimulus that is capable of overcoming the movement of K+ ions that is causing this value to be way below threshold
Normally start of on -70, but during hyperpolarization we’re even lower that that so it needs to overcome the hyperpolarization and bringing us back to threshold again
We have two diff refractory periods based on where we are in action potential
In both scenarios, what we’re trying to accomplish here is placing restrictions and limitations on the frequency in which a neuron can generate and transmit an action potential
Don’t want to elicit them to often that can have negative remifficants

Question 59

Conduction of Action Potentials-
Refractory period not applicable to the whole axon, just to where the specific event is taking place, when action potentual is generated at axon hillock, there’s an electrical current going to depolarize the axon membrane next to it which will initiate domino effect of the action potentials from each region in axon until it gets to terminal synapse- how info is passed along across an axon to get to synapse,

Answer 59

Refractory period not applicable to the entirely of that neuron/axon
Just that discrete region where events are taking place
Applies to all events occurring in action potential
Sight that action potential is generated; usually at axon hillock, there’s an electrical current that’s going to depolarize the neighboring of the axon membrane, which will help to initiate our events
Neuron that lacks any level of insulation ,going to have voltage gated channels found all along the length of axon
So when action potential occurs initially, Na+ are going to enter the axon and hte polarization event will open up a nearby voltage gated channel so that more sodium ions cna start ot move
Lead to forward propagation
Domino effect
Behind the process we’re going to have our K+ channels bc they’re slower to open
Happens further along action potential
Going to see K+ ion movement start ot head outwards
Eventually both these channel types will close and cycle will end
And reach a state where nothing will happen and reach resting state
At that spot in the axon, it has completed itself
But we’ve been initiating a wave so in row 2 we have the initiation of Na+ and movement into the axon, and eventually overtime as we allow that process to occur, K+ will exit out and eventually it will be back to resting state (where inside of cell is negative and outside cell is positive)
We’re initiating waves of events that continue to work its way downstream- like domino effect
Each action potential ccle will initiate the next one
So the closest one to it
Going to keep happening until transmission reaches the end of the neuron
Action potentials meant to travel in one direction → which is towards the synaptic terminals
We want that to be the case, bc we want to ensure we’re directing the signal where it needs to be
When it comes to voltage gated sodium channels, they will have an inactivated state
Inactivation sodium channels that are occurring behind that zone of depolarization while prevent action potential form traveling backwards
And ensure we have appropriate movement towards synaptic knobs
While this communication is electrical, the movement of the signal wouldn’t be the same of current traveling through a wire
Nerve signals are slower and it’s intensity does not dissipate the further they travel, which is something that can be seen when your conducting a current through a wire
Something that’s beneficial about domino effect is that the ion gradient that’s established across plasma membrane allows for the signal to be self propagating as it works it’s way across
Ion movement influencing ion movement to restart this process and initiate htat all or nothing event as we work our way down the length of that axon

Question 60

Adaptation of Axon Structure

• with bigger diameter of axon, there is a higher rate of conduction of a signal bc there is grater flow of currents
• also higher degree of myelination (myelin sheath which is in Schwann Cells in PNS and olgodendrites in CNS), as myelination will increase conduction velocity

Answer 60

The velocity or the rate at which were able to conduct these signals can vary from one nerve fiber to another depending on where it is
When there are places in which you would need to have a fast response, you want a higher rate of conduction
At places where slower response will not lead to negative outcome, that will have conduction velocities that are a little slower
Ex where they might be slower could be your gut, digestive tract
When it comes to the axon, the diameter plays a role
The idea is that the larger the axons diameter, the faster it conducts an impulse
Larger axons can conduct an impulse more quickly bc they offer less resistance of the flow of those local currents and that brings adjacent areas of the membrane to the threshold faster
There is also the degree of myelination
Presence of myelin sheath can help to significantly increase the speed of propagation, ability to transmit that signal along the length of the axon
Conduction velocity increases with the degree of methylation
Could have lightly myelinated fibers- will conduct slowly than those that are heavily myelinated
The absence of a myelin sheath will reduce conduction velocity as well
Myelination helps to increase the conduction velocity
Myelin is a spiraling layer
Going to surround nerve fiber and here we see Schwann Cells so this will be insulation event occurring within PNS, but within CNS oligodendrocytes will accomplish this task
A myelin sheath consists of plasma membrane of glial cells
As a result, myelin sheath will have similar composition of plasma membrane of a glial cell or plasma membrane in general
Plasma membrane is mostly lipid and can find proteins in there
So there’s a lot of phospholipid and cholesterol found within myelin sheath

Question 61

Saltatory Conduction
(how does this process work in terms of the rising and falling of action potentials? I get its insulated due to myelin sheath, which makes the current from depolarization last, but does that mean that once initial depolarization occurs, there will be no rising and falling of action potential (Na+ coming in, then K+ coming out for subsequent areas to be conducted?)
not sure if conducted is correct word even

Answer 61

The velocity or the rate at which were able to conduct these signals can vary from one nerve fiber to another depending on where it is
When there are places in which you would need to have a fast response, you want a higher rate of conduction
At places where slower response will not lead to negative outcome, that will have conduction velocities that are a little slower
Ex where they might be slower could be your gut, digestive tract
When it comes to the axon, the diameter plays a role
The idea is that the larger the axons diameter, the faster it conducts an impulse
Larger axons can conduct an impulse more quickly bc they offer less resistance of the flow of those local currents and that brings adjacent areas of the membrane to the threshold faster
There is also the degree of myelination
Presence of myelin sheath can help to significantly increase the speed of propagation, ability to transmit that signal along the length of the axon
Conduction velocity increases with the degree of methylation
Could have lightly myelinated fibers- will conduct slowly than those that are heavily myelinated
The absence of a myelin sheath will reduce conduction velocity as well
Myelination helps to increase the conduction velocity
Myelin is a spiraling layer
Going to surround nerve fiber and here we see Schwann Cells so this will be insulation event occurring within PNS, but within CNS oligodendrocytes will accomplish this task
A myelin sheath consists of plasma membrane of glial cells
As a result, myelin sheath will have similar composition of plasma membrane of a glial cell or plasma membrane in general
Plasma membrane is mostly lipid and can find proteins in there
So there’s a lot of phospholipid and cholesterol found within myelin sheath

Question 62

Module 4: Synapse

Question 63

Diff synapses (electrical- for direct communication via gap junctions from one neuron to another, mostly seen in embryonic development, and is fast; chemical- our focus which carries neurotransmitters between neurons at the synapse)

Answer 63

Neurons communicate with other cells at synapse
Synapse is really small expansive space that provides opportunity for 2 neurons to communicate with each other
Synapse can be electrical or chemical
Electrical less common
Consists of gap junctions
Gap junctions will allow for direct communication to connect cytoplasm of adjacent neurons
Will allow ions and small molecules to flow directly from one neuron to the next
Fast
Simple way to synchronizing activity of interconnected neurons
Ex: jerky movements in eyes (stereotyped movements)
See it a lot more during embryonic nervous tissue
Idea of guiding early neuronal development
Over time as nervous system develops transition to chemical synapses
Most synapses are chemical synapses
Our focus with neurotransmitters that postsynaptic neuron will receive and respond to

Question 64

How neurotransmitters get across synapse to post synaptic cell (1. starts will electrical at the end of axon (axon terminal) and shifts to chemical 2. Calcium (Ca+) goes into neuron via voltage gated Ca2+ channel and causes synaptic vesicle containing neurotransmitter to fuse with its membrane

3. Vesicle does this and releases neurotransmitter into synapse
4. Neurotransmitter travels across synapse and binds to postsynaptic ligand gated ion channel, where a downstream response occurs; could be excitatory (like another action potential) or inhibitory depending on what the message is and how it is done

Answer 64

At this point conducting electrical signal, we need to shift focus from electrical to chemical
Here we have synapse, small space between pre synaptic cell and postsynaptic cell
Before and after that synapse which is a small expansive space
Chemical synapses
Common
Release and reception of a chemical messenger- referred to as neurotransmitters
1. Have action potential
Been working its way along its axon
Reaches the terminus (synaptic bulbs)
2. Action potential arrives and going to influence a voltage gated Ca2+ channel
Voltage gated calcium channel found on presynaptic membrane going to open
Impact: cause synaptic vesicles containing neurotransmitters to fuse at synaptic cleft
Merging with presynaptic membrane in process called exocytosis
3. Molecules will diffuse across synaptic cleft
Once a vesicle dispenses of its neurotransmitter so it exits out into the cleft ,then the empty vesicles will dropped back into cytoplasm to be refilled with neurotransmitters
Cycling through picking up and dropping off
Will bind to ion ligand gated receptor
Located at postsynaptic cell
4. The neurotransmitter binding to ligand will cause channels to open and these channels will allow for movement (in this ex Na+ and K+)
The movement of ions can help to achieve some type of downstream impact on that postsynaptic cell
Might be excitatory, might be inhibitory depends on info being relayed and how iys being delayed
Sum up:
End of electrical and shift into chemical
Have voltage gated calcium channel
Then have ligated gated ion channel

Question 65

Excitatory postsynaptic potentials:

Answer 65

We’ve not gotten to that postsynaptic neuron
Question becomes now what
What’s that postsynaptic neuron going to do
There can be a local change that occurs
Result in conversion of that chemical signal through that neurotransmitters to an electrical one
Ligand gated channels found on postsynaptic neuron are going to be less sensitive to changes in membrane potential than voltage gated ion channels
There might need to be added mechanism s that we need to utilize to induce an electrical response in this post synaptic cell
There are ligand gated channels just about K+, or just about Ca+, or can be Na+ and K+
There is some level of specificity with a molecule and what protein it will interact with so it varies
Postsynaptic side has two major categories
EPSP
Excitatory postsynaptic potentials
Depolarization events (decreasing magnitude → increasing membrane potential) excite or elicit another action potential to take place in postsynaptic cell
Causing a rise in membrane potential
In this image, we have depolarization event that does not reach threshold
But that’s what an EPSP works towards → reaching threshold
So it results in depolarization and bring the membrane potential towards threshold
May reach threshold or not but capable of triggering action potential if that stimulus is stronger to reach -55
EPSP is on postsynaptic cell to elicit an additional response downstream
IPSP

Question 66

IPSP- Inhibitory postsynaptic potentials (which in inhibitory post synaptic potential- results in hyperpolarization; which is making the membrane potential more negative below resting potential by K+ going out of cell, Na+ not being touched, and Cl- coming into cell down its pressure gradient which both K+ coming out of cell and Cl- coming into cell makes the cell potential negative and results in no action potential even thought of being done as it is further from threshold that before at resting potential- do NOT want action potential for inhibitory post synaptic potentials

Answer 66

IPSP going to be associated with hyperpolarization
Going to move the move the membrane potential further away from threshold and decrease the likelihood of an action potential taking place
Expect for EPSP to be associated with increased permeability for Na+ ions
Expect for IPSP to be associated with increased permeability for K+ ions
That is the case, didn’t include Cl- ions in discussion but you can also have increased permeability to Cl- in an IPSP
In IPSP Na+ not affected
We could induce Cl- to enter cell down its concentration gradient to help with making cell more negative for hyperpolarization

Question 67

Different types of responses with EPSP and IPSP
(looking at summation, adding up of EPSP signals and IPSP signals to determine what EPSP will do
A: subthreshold; this is two EPSP’s but far away from each other and each singular one is not enough to build up to a threshold and can’t combine them (summate them) bc they’re too far apart = no action potential (but if there was another EPSP on top of one of them, it’s so close to threshold at their EPSP peaks that it would most likely hit threshold and result in aciton potential but that is an IF
B: Temporal summation; = time! The same pre synaptic neuron telling the post synaptic neuron to GO via EPSP signals back to back to back to back- results in enough stimulus via EPSP signals to make an action potential
C: Spatial Summation; combination of two post synaptic neurons saying GO via EPSP but just once each but since its both its enough to result in action potential (E1 + E2)
D: Spatial summation of EPSP and IPSP; canceling each other out, results in IPSP winning ultimately as it is preventing an action potential from happening even tho it is not hyper polarizing for long due to next EPSP to cancel it out

Answer 67

Think about how does an neuron decide how to respond to reception of EPSP and IPSP
We look at summation- adding up of all the signals received
Total amount of signals a neuron receives and that’s going to impact whether the combined event is exciting or inhibited
A single EPSP is not enough for an action potential
But if we there are many excitatory terminals that are firing on that membrane of the postsynaptic cell or if the rate of the delivery is fast enough
Then the likelihood of reaching threshold (action potential) increases

Question 68

Termination of Neurotransmitter Signaling (After response is triggered due to neurotransmitter binding to ligand at postsynaptic neuron, want the chemical synapse to return to resting state in order for their to be a balance and now too much stimulation

• therefore neurotransmitters are cleared from synaptic cleft until additional stimulus results
• However, if there is something messing with this process of termination = no good
• ex: DIPF as an irreversible inhibitor of adenylchlolinesterase
• acetylcholinesterase function is to allow normal function of nervous system to take place
• so if we remove it, by inhibiting it and this is irreversible!, then we will have downstream responses that are inappropriate, too much neurotransmitters at synaptic cleft that will thus bind to post synaptic neuron, which is NOT good as can lead to uncontrolled skeletal movement and then eventually death- used as a biological warfare

Answer 68

As its important to initiate this process, equally important it ends
Want to consider the termination of neurotransmitter signaling
Bc that presence of a neurotransmitter can elicit a downstream response so after the downstream response is triggered (whether excitatory as a result of the summation or inhibitory), chemical synapse needs to return to resting state, so we want to make sure that there are no neurotransmitter molecules found at synaptic cleft anymore
One can imagine that anything that blocks termination from occurring can have significant impacts
Role of biological warfare and sarin gas and how this can trigger paralysis and death
Irreversible
DIPF, which is irreversible inhibitor of acetylcholinesterase
Acetylcholinesterase- its role in allowing normal function of the nervous system to take place
If we have irreversible inhibitor of acetylcholinesterase- remove acetylcholinesterase concentration at synaptic cleft, then what ends up happening in that scenario is a ton of downstream responses that are inappropriate- too much
Lead to uncontrol skeletal movement, can eventually cause death which is why it is utilized as neurological warfare
Another way to think about this in terms of neurotransmitters is that of psychoactive drugs and how certain types of substances can relate in our body as it relates to nervous system as well

Question 69

Different ways termination can occur when we don’t want neurotransmitters to bind to post synaptic receptors BUT neurotransmitters are released:

1. Neurotransmitters released and diffused into extracellular fluid or supporting cell, glial cells, and then reabsorbed by neurons
2. Neurotransmitters being released nad inactivating enzyme, found in either post synaptic neuron or synaptic cleft, which degrades the Neurotransmitters via enzmyatic breakdown, which means it will no longer be the shape of the OG Neurotransmitters, so it won’t be able to bind to ligand as ligand is shape specific; the mini Neurotransmitters can either go back into pre synaptic cell to be recycled and used again when needed, or goes out into extracellular fluid
3. Neurotransmitters released and gets uptaken back into pre synaptic neuron and there it is either put back into vesicles to be used again OR gets degraded there inside the pre snyaptic neuron

Answer 69

If we turn on a response, eventually we want ot turn it off, don’t always want a downstream cascade bc that defeats homeostasis bc we want balance in nervous system
Signal cessation- have to think about how we turn off this response so that we don’t have prolonger communication
in this scenario, the stimulus on the presynaptic neuron is the neurotransmitter
One easy solution, if we don’t want to elicit a response for a postsynaptic neuron, stop releasing the neurotransmitter
Stop firing the presynaptic neuron
Other options:
Release of neurotransmitters and subsequent diffusion of synaptic cleft (not visualized here)
Floating away its extracellular fluid
This may be absorbed by supporting cells, glial cells, and then returned to the neurons
A. Another option which is shown in portion A, which is enzymatic breakdown of neurotransmitter in the synaptic cleft (degradation)
Degradation event takes place in synaptic cleft
Have neurotransmitters released by presynaptic neuron (chemical messengers)
And then get broken down by inactivating enzyme on postsynaptic receptor into smaller pieces and no longer can bind to neurotransmitter receptor on postsynaptic receptor
Bc we know that ligand binding is specific so if it doesn’t fit, it won’t bind and thus not elicit a response
It is possible for degrading neurotransmitters to be reabsorbed and then recycled by the pre synaptic cell in order to generate more neurotransmitters to be utilized when it’s needed
Showing you inactivating enzyme present on postsynaptic neuron but enzyme may also be present at the cleft
B. reuptake of neurotransmitter by presynaptic neuron
Can also have reuptake in the absence of enzymatic degradation
Synaptic knobs can reabsorb neurotransmitters in the state that they are and can simply be stored in vesicles again OR you can degrade them once they are back in presynaptic neuron
Cna help to stop any downstream communication you are trying to avoid to happen
Think about how this related to cell communication