PHYS 435 Lectures 7-9

In chemical synaptic transmission, vesicles would naturally fuse with the plasma membrane and release their NTs. Why then do we need SNARE protein complexes?

Although vesicle exocytosis would occur naturally over time, this process would be painfully slo. SNARE protein complex increase the rate of fusion MANY fold so that more synaptic transmission can occur

What is a simple definition for an excitatory stimulus?

An excitatory stimulus is any stimulus that makes an action potential more likely to occur

What is a simple definition for an inhibitory stimulus?

An inhibitory stimulus is any stimulus that makes an action potential less likely to occur

Gap junctions are found between what three types of cells?

1. Cardiac cells 2. Smooth muscle cells 3. Some brain cells

In three steps, discuss the POSTSYNAPTIC events that occur in the process of chemical synaptic transmission. Assume that you're dealing with an INHIBITORY synapse

1. NT in synaptic cleft binds to postsynaptic receptors 2. Ligand-gated channels open (chemical gating) 3. Either K+ flux out of the cell or Cl- flux into the cell to pull the neuron away from threshold potential (makes AP less likely)

What are two examples of myelinated neurons, and where would we expect to find them?

1. Oligodendrocytes in the CNS 2. Schwann cells in the PNS

What are the four ways in which excess NT can be removed from the synapse

1. Reuptake 2. Transportation to nearby glial cells where they are degraded 3. Diffuse away from the receptor site 4. Enzymatic deactivation

In three steps, discuss the POSTSYNAPTIC events that occur in the process of chemical synaptic transmission. Assume that you're dealing with an EXCITATORY synapse

1. The NTs in the synapse binds to post-synaptic receptors on the postsynaptic cell 2. Ligand-gated channels open (chemical gating) 3. Cations flow through (mostly Na+ or Ca2+) to depolarize the post-synaptic membrane

What three processes/structures are at functioning when the membrane is at resting potential?

1. The Na+/K+-ATPase pump 2. K+ leak channels 3. Na+ leak channels

One way to modulate chemical synapse strength is through the use of neuromodulators. These neuromodulators can be used to activate ______________ at ______________ receptors

2nd messengers; non-synaptic

Define pacemaker potential

A spontaneously occurring graded potential change that only occurs in specialized cells

W

C

_______________ occurs when ion movement reduces the charge imbalance. In other words, the charge is moving towards ________________

Depolarization; Zero

Is the absolute amplitude of a graded potential small or large. What about an action potential?

Graded potential: Smaller Action potential: larger

W

L

_____________ refers to the development of a charge reversal (now positive)

Overshoot

One way to modulate chemical synapse strength is through the use of neuromodulators. Neuromodulators are usually small ___________________, that are co-released with _______________

Peptides; NTs

Draw diagram of two hypothetical graded potentials, one caused by a high intensity stimulus, and the other caused by a low intensity stimulus

See class notes page 74 or paper drawing

In the process of chemical synaptic transmission, SNARE proteins pull the vesicle to the plasma membrane, resulting in fusion of these two membranes. Upon fusion, a hole forms that allows NTs to exit the axon terminal and cross the synaptic cleft. What is the hole referred to as?

The fusion pore

What are active zones?

These are the "release regions" on the presynaptic neuron where many vesicles are docked

Presynaptic Facilitation is one way in which you can modulate chemical synaptic strength. Describe what is occurring in the process. Provide some context before describing the process. What is one important thing to note about this process?

To begin, in presynaptic facilitation, there are 3 neurons rather than just two. We can call these neurons A, B, and C. Neuron B is what we would typically think of as the presynaptic neuron (The "King") and Neuron C is what what we would typically call the post-synaptic neuron (the "Minions"). The 3rd neuron, A can be thought of as an "Advisor to the King," meaning neuron A influences the output of neuron B. In pre-synaptic facilitation, the advisor A secretes NTs which bind to the King, B. This increases the release of NTs from B to C (King to minions). It is important to note that A can cause B to facilitate BOTH Excitatory and Inhibitory synapses

One way to modulate chemical synapse strength is through via long-term potentiation. In 8 steps, describe this process. Make sure to differentiate between the effects of when a small and large amount of glutamate is released

1. A high-frequency action potential propagates to the axon terminal of a presynaptic cell 2. AP triggers vesicle exocytosis of glutamate 3. Glutamate binds to both the AMPA and NMDA receptors in the post-synaptic membrane. Note, if only a small amount of glutamate binds to the AMPA receptor, not enough Na+ is released in step 4 to cause sufficient depolarization to open the NMDA channel, so nothing happens. However, if a large amount of glutamate is released, proceed to step 4 4. When a large amount of glutamate is released, the AMPA receptor opens, allowing for a large amount of Na+ to entry the post-synaptic membrane causing a major depolarization of 20-30mV 5. Depolarization of the post-synaptic membrane drives the Mg2+ ion out of the pore in the NMDA, causing it to open 6. Ca2+ fluxes through the NMDA receptor into the post-synaptic membrane, which activates second-messenger systems 7. Activation of second messenger symptoms results in a long-lasting increase in glutamate receptors and sensitivity 8. Via a retrograde messenger whose mechanism is not yet understood, changes to the Presynaptic neuron occur that create a long-lasting increase in glutamate synthesis and release Cycle repeats

Chemical synaptic transmission (i.e. communication between cells via NTs) can occur in three different orientations. What are these three positions (describe each)? Make sure you are able to draw

1. Axo-dendritic: The axon terminal of a presynaptic neuron sends its NTs to the dendrites of a post-synaptic neuron 2. Axo-somatic: The axon terminal of a presynaptic neuron sends it NTs to the soma (cell body) of a post-synaptic neuron 3. Axo-Axonic: The axon terminal of a presynaptic neuron sends its NTS to the axon of a post-synaptic neuron See page 83 of class notes for a crude drawing

What are two synonyms for Ligand-gating?

1. Chemical gating 2. Ionotropic receptor (this is the most commonly used)

What are two reasons that a larger than normal stimulus is required to propagate and action potential during the relative refractory period?

1. Fewer sodium channels are closed (some are inactivated) 2. Some K+ channels are still open, which opposes depolarization by Na+ entry

In four steps, discuss the PRESYNAPTIC events that occur in the process of chemical synaptic transmission

1. First, an action potential reaches the axon terminal 2. This causes voltage-gated Ca2+ channels to open and calcium floods into the cell 3. Ca2+ activates vesicle exocytosis 4. The neurotransmitters diffuse across the synaptic cleft (tiny gap of only about 15nm)

What are two synonyms for graded potentials?

1. Generator potentials 2. Sensory receptor potentials

What are the two types of membrane potentials that are of major functional significance? Which comes first?

1. Graded potentials (come first) 2. Action potentials

What are the two possible types of post-synaptic receptors in chemical synaptic transmission

1. Ionotropic receptors (ion channels) 2. Metaba tropic receptor (G protein/2nd messenger)

One way to modulate chemical synapse strength is through the use of neuromodulators. Neuromodulators activate 2nd messengers at non-synaptic receptors. What are three examples of non-synaptic receptors?

1. Lateral Pre-synaptic receptors (these are not actually at the synapse, but rather on the lateral side of the axon terminal) 2. Lateral Post-synaptic receptors (these are not actually at the synapse, but rather on the later side of the post-synaptic dendrite) 3. Receptors on nearby neurons that are neither the pre-synaptic nor post-synaptic neuron in questions

Name, but do not describe the five Modulations of Chemical Synaptic Strength

1. Presynaptic Inhibition of Facilitation 2. Use of Neuromodulators 3. Persistence of NTs leading to Desensitization (of receptors) 4. Long-term Potentiation 5. Modulating synapse strength via drugs and disease

Beginning and ending at resting membrane potential, describe the seven-step process by which an action potential occurs

1. Steady Vm is at -70mV (near E_k), and P_k > P_Na (i.e. the membrane is more permeable to K+ than Na+) due to the higher presence of K+ leak channels 2. Local membrane is brought to threshold voltage of -55mV by a depolarizing stimulus 3. Current through opening voltage-gated Na+ channels rapidly depolarizes the membrane, causing more Na+ channels to open 4. Inactivation of Na+ channels AND delayed opening of voltage-gated K+ channels halts membrane depolarization 5. Outward current through open voltage gated K+ channels repolarizes the membrane back to a negative potential 6. Persistent current through slowly closing voltage-gated K+ channels hyperpolarizes the membrane toward E_k; Na+ channels return from inactivated state to closed state (without opening) 7. Closure of voltage-gated K+ channels returns the membrane potential Make sure you are able to label where each step is occurring on a drawing on an action potential (see page 76 of printed class notes)

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A

Do a large or small number of ions cross the membrane during an action potential?

A VERY small number of ions actually cross the membrane during an action potential

Define action potential. Is it conducted with decrement (gradual reduction)? Does it have a threshold or refractory period?

A brief, all-or-none depolarization of the membrane, which reverses polarity in neurons; has a threshold and a refractory period and is conducted without decrement

Why are neurons referred to as "polarized?"

A cell is "polarized" because its interior is more negative than its exterior

Define synaptic potential. Is it polarizing, depolarizing, or both?

A graded potential change produced in the postsynaptic neuron in response to the release of a neurotransmitter by a presynaptic terminal; may be depolarizing (an excitatory postsynaptic potential or EPSP) or hyperpolarizing (an inhibitory post-synaptic potential)

Define receptor potential

A graded potential produced at the peripheral endings of afferent neurons (or in separate receptor cells) in response to a stimulus

Define graded potential. Is it conducted with decrement (gradual reduction)? Does it have a threshold or refractory period?

A potential of variable amplitude and duration that is conducted decrementally; has no threshold nor refractory period

What are axon collaterals?

Axon collateral are the "branches" that split off the axon of a presynaptic primary neuron in divergence in order to communicate with multiple post-synaptic secondary neurons

One way to modulate chemical synapse strength is via long-term potentiation. Why is long-term potentiation said to be be a mechanism of learning and memory?

Because each repetition of the long-term potentiation cycle increases the synaptic strength, each cycle is said to contribute to the "memory" of the synapse.

Why can't action potentials summate like graded potentials?

Because of the absolute and relative refractory period do not allow action potentials to "come in contact" and have a cumulative effect

What is multiple sclerosis caused by?

Caused by autoimmune destruction of myelin

What is meant by the term neuronal convergence, or simply, convergence? Include an example of where we would find this in the body

Convergence describes when multiple presynaptic primary neurons in the CNS converge onto a single postsynaptic secondary neuron. Convergence allows information from many sources to influence a single cell's activity. Examples of convergence can be seen in efferent motor neurons required to say, move the hand

Broadly speaking, what opens the voltage-gated sodium and potassium channels during an action potential?

Depolarization

Describe what happens when a depolarizing graded potential occurs. Also draw an example of this occurring

Depolarization and graded potential are caused by a chemical stimulus. Inward positive current through ligand-gated cation channel depolarizes a region of the membrane, and the local current spreads depolarization to adjacent regions. For drawing, see page 74 of class notes or paper drawing

One way to modulate chemical synapse strength is through the persistence of NTs, which leads to desensitization of receptors. Describe how and why this happens.

Desensitization involves a changing of the receptors through signal transduction cascades, wherein the receptors become desensitized due to persistent phosphorylation. The receptors are then engulfed by the cell via clathrin-coated pit mediated endocytosis

What is meant by the term neuronal divergence, or simply, divergence? Include an example of where we would find this in the body

Divergence describes when a single primary presynaptic neuron in the CNS splits into multiple branches called axon collaterals in order to communicate with multiple post-synaptic secondary neurons. Divergence allows one cell to affect multiple pathways Common in skeletal muscles

What is the absolute refractory period and what causes it? Answer this question in the context of an action potential, referring to the actions of specific channels

During the action potential, a second stimulus, no matter how strong, will not produce a second action potential. That region of the membrane is then said to be in the absolute refractory period. This occurs during the period when the voltage-gated Na+ channels are either already open or have proceeded to the inactivated state during the first action potential the inactivation gate (ball and chain) that has blocked these channels must be removed first by repolarizing the membrane and closing the pore before the channel can reopen to a second stimulus.

What is strength in mV of the EPSP at an excitatory post-synaptic membrane receptor. What does this indicate about what must happen in order for an AP to propagate?

Each binding of an NT to an excitatory post-synaptic membrane receptor results in only a very small depolarization of about 0.5mV per NT-R complex. Seeing as how the threshold potential may be 15mV away from resting Vm, this indicate that we need to summate many EPSPs in order to propagate an action potential

True or false: Graded potentials are refractory

False

True or false: An action potential is characterized by rapid flux of sodium out of the cell, followed by a slower flux of potassium into the cell

False: An action potential is characterized by a rapid flux of sodium INTO the cell (causes depolarization), followed by a much slower flux of potassium OUT of the cell, causing repolarization and eventual hyperpolarization

True or false: Graded potentials accumulate strength rapidly with distance. Explain

False: Graded potentials DECAY rapidly with increasing distance along the membrane

True or false: Myelination of an axon decreases the velocity with which an AP propagates. Explain

False: Myelination majorly increases the velocity of AP propagation by as much as 225 times

What is the relative refractory period? Answer this question in the context of an action potential, referring to the actions of specific channels

Following the absolute refractory period, there is an interval during which a second action potential can be produced, but only if the stimulus strength is considerably greater than usual. During the relative refractory period, some but not all of the Na+ channels have returned to resting state. With fewer Na+ channels available, the magnitude of the action potential is temporarily reduced. in addition some of the K+ channels that repolarized the membrane are still open. Outflow of K+ through these channels opposes some of the depolarization produced by Na+ entry, making it more difficult to reach threshold until a stronger stimulus occurs.

What is the purpose of gap junctions (electrical synapses)? Discuss the speed associated with gap junctions

Gap junctions are small channels linking the cytosol of adjacent cells in order to conduct electrical signals directly from cell to cell VERY RAPIDLY

Where do graded potentials propagate to and from? What about action potentials?

Graded Potentials: Dendrites >>> soma Action potentials: Axon Hillock>>> Axon terminal

What are graded potentials and action potentials initiated by?

Graded Potentials: Initiated by environmental stimulus (receptor), by neurotransmitter (synapse), or spontaneously Action potential: Initiated by a graded potential

What is a unique property of graded potentials with regard to their cumulative effects? Explain using some examples

Graded potentials can summate with each other, meaning that their effects are cumulative. For example, two small depolarizing graded potentials can summate to form one large depolarizing graded potential. Additionally, a depolarizing graded potential and a hyperpolarizing graded potential can summate to create a net neutral (zero) effect

Can graded potentials be both a depolarization or a hyperpolarization? What about action potentials?

Graded potentials: Can be both a depolarization or a hyperpolarization Action potential: Is only a depolarization

With regard to gating, what types of channels are graded potentials associated with? What about action potentials?

Graded potentials: Ligand-gated channels Action potentials: Voltage-gated channels

What do the mechanisms of graded potential depend on? What about action potentials?

Graded potentials: Mechanism depends on ligand-gated ion channel or other chemical or physical changes Action potentials: Mechanism depends on voltage-gated ion channels

Do graded potentials have a refractory period? What about action potentials?

Graded potentials: No Action potentials: Yes

Do graded potentials have a threshold potential? What about action potentials?

Graded potentials: No Action potentials: Yes

Do graded potentials have variability in their amplitudes? What about action potentials?

Graded potentials: Yes Action Potentials: No

_____________ is the development of even more negative charge inside the cell. Here the charge moves below ______________

Hyperpolarization; resting membrane potential

I

I

What is the difference between temporal and spatial summation of postsynaptic potentials (PSPs). Describe what happens with regard to summation in both cases

In temporal summation, there is only one PSP input. In spatial summation there are multiple PSP inputs. Because PSPs degrade over time, the temporal summation of PSPs may or may not have a cumulative effect, depending on the amount of time between each input if enough time is allowed to pass between each input.

Where is one place in the body we would expect to find unmyelinated neurons? Why does this make sense in the context of the speed with which myelinated neurons propagate action potentials?

In the GI tract. This makes sense because unmyelinated neurons are slower acting than myelinated neurons. However, the process of digestion doesn't need to occur super fast, so these unmyelinated neurons work very well in this environment

The slower opening of voltage-gated _______ channels explains the repolarization and after-hyperpolarization phases that complete the action potential

K+

Describe the local current flow in a post-synaptic excitatory synapse

Local current flow moves away from the receptor site and towards the axon Hillock

Describe the local current flow in a post-synaptic inhibitory synapse

Local current flow moves toward the receptor site and away from the Axon Hillock

While unmyelinated axons are primarily utilized in places like the digestive system when you are in "no hurry," myelinated neurons are utilized when you need speed. Therefore, what type of neurons would we expect to be myelinated?

Motor neurons

What is the single most common disease of the CNS nervous system among young adults? What is the prevalence of this disease, and what is the average age of onset?

Multiple sclerosis; occurs in 1 in 1000 people, and average onset is 30 years of age

The rapid opening of voltage-gated ________ channels explains the rapid depolarization phase at the beginning of an action potential

Na+

Do voltage-gated potassium channels possess the same ball and chain structural mechanism as voltage-gated potassium channels?

No they do not

Can an action potential reveal anything about the intensity of the stimulus? Explain

No, because action potentials are all or none, their intensity does not vary in proportion to the stimulus. Thus, the only information about the intensity of the stimulus that we can gain from an action potential is that the stimulus was at least at threshold

Graded potential tend to dissipate completely over approximately what distance?

Only about 2mm

Communication between neurons is based on changes in the membrane's what?

Permeability to ions

Compare the length (as in time) of Postsynaptic potential (EPSPs or IPSPs) to action potentials. Provide four reasons for this

Post-synaptic potentials are brief, but longer than APs because: 1. NTs rapidly bind and unbind receptors reversably (R + NT <<<<>>>>> R:NT) 2. NTs can be reuptaken in the presynaptic terminal and/or... 3. NTs can diffuses away from the synapse and/or... 4. NTs can be destroyed by enzymes via catabolism (and the products of catabolism are reuptaken into the presynaptic axon terminal)

Describe the process of voltage-gated sodium channels going from closed to inactivated during an action potential. Describe the structure of the ball and chain in your answer

Prior to receiving the excitatory signal, the sodium channel is closed, with the ball and chain connected to, but not plugging the channel. Once threshold is reached, the channel opens and a tiny bit of sodium is allowed to pass through the channel. However the flow of sodium is quickly stopped when the ball and chain plugs the pore, resulting in inactivation of the channels

Broadly speaking, what closes the voltage-gated sodium and potassium channels during an action potential?

Repolarization

_____________ is movement back toward the (-) resting potential

Repolarization

What is the process by which action potentials "jump" from Node of Ranvier to Node of Ranvier in myelinated neurons referred to as?

Saltatory conduction. it is important to note, however, that an action potential does not actually jump from region to region, but rather is regenerated at each node of Ranvier

Draw a diagram depicting strength of action potentials during refractory period relative to strength of stimulus over time

See class notes page 78 or paper drawing

The rapid opening of voltage-gated Na+ channels explains the rapid depolarization phase at the beginning of an action potential. Draw this process as a positive feedback loop

See page 77 of class notes or paper drawing

The slower opening of voltage-gated K+ channels explains the repolarization and after-hyperpolarization phases that complete the action potential. Draw this process as a negative feedback loop

See page 77 of class notes or paper drawing

In three distinct stages, draw the propagation of an action potential from Axon Hillock to axon terminal

See page 79 of class notes or paper drawing

On a graph of membrane potential vs. time, draw out the following PSP summations with the assumptions the A & B are excitatory synapses, while C is an inhibitory synapse. Label each input as a temporal or spatial summation 1. Two inputs of A with sufficient time between inputs 2. Two inputs of A with less time between inputs 3. Initial input of be, with sufficient time between simultaneous input of A & B 4. Sequential input of A, A, B, B with little time between inputs 5. Input of C with sufficient time between simultaneous input of A & C

See page 87 of printed notes, or paper drawing

Graded potentials are important in signaling over ____________ distances, whereas action potentials are _________-distance signals that are particularly important in neuronal and muscle cell membranes

Short; long

Which region of the neuron has the highest density of voltage-gated Na+ channels?

The Axon-Hillock. This is why we say that the action potential starts here

What is the Nernst/equilibrium potential of Ca2+ and why is this important

The Nernst potential for Ca2+ is SUPER positive (as high as 127mV). This means that the concentration of intracellular Ca2+ is MUCH higher than the extracellular Ca2+. This is important during the process of exocytosis of NTs out of the presynaptic membrane and across the synapse. Due to the massive concentration gradient of Ca2+, as soon as Ca2+ channels open, Ca2+ will flood into the cell, stimulating the exocytosis of vesicle-bound NTs across the synapse

What is the after-hyperpolarization and what causes it?

The after-hyperpolarization refers to the period during an action potential in which the membrane potential becomes more negative than -70mV and then returns to -70mV. The reason for the hyperpolarization period is because the voltage-gated K+ channels are slow to close, meaning that the flux of K+ ions out of the cell hyperpolarizes the membrane past its resting potential

Describe the channel locations of nonmyelinated neurons compared to myelinated neurons. What does this indicate about the time it takes for each neuron to propagate an action potential

The channels in unmyelinated neurons are spread fairly evenly throughout the axon and time is required for each patch to depolarize. Conversely, myelinated neurons have their transport channels clumped together in the gaps between myelin sheaths (known as Nodes of Ranvier). Action potentials then "jump" from Node of Ranvier to Node of Ranvier, completely bypassing the myelinated regions, in a process called saltatory conduction, which is MUCH faster than waiting for each individual region of the axon to depolarize

Action potentials are not graded by stimulus size. What then determines the appearance/characteristics of an action potential?

The conditions of the ECF (check this answer with Dr. Lokuta)

A typical neuron has a dendritic region and an axonal region. Broadly speaking, what is the function of each of these regions

The dendritic region is specialized to receive information, whereas the axonal region is specialized to deliver information (neurotransmitters are usually released from axonal regions onto dendritic regions)

What is the technical term for the ball-and-chain structure that modulates influence of Na+ in voltage-gated Na+ channels?

The inactivation gate

Define threshold potential

The membrane potential at which an action potential is initiated

When NTs bind to an excitatory post-synaptic receptor. What is the net effect?

The net effect is a very small depolarization

The size of a graded potential is proportionate to what? What does this actually mean withregard to the distance over which a graded potential can act

The size of a graded potential is proportionate to the intensity of the stimulus. Therefore, if a higher intensity stimulus is present, the graded potential will act over a greater distance along the membrane.

Define resting potential

The steady potential of an unstimulated cell

How is the velocity with which an action potential propagates down an axon related to the diameter of the axon? Why is this?

The velocity of an action potential is positively correlated with the diameter of an axon. This is because axon with larger diameter contain more cytosol, which contains more transporters. Thus, larger diameter axon will increase the velocity of an AP

Define membrane potential

The voltage difference between the inside and outside of a cell

Define potential or potential difference

The voltage difference between two points due to separated electrical charges of opposite sign

What is the defining characteristic of excitable membranes?

They are able to propagate action potentials

Describe the speed with which voltage-gated potassium channels open and close?

They open and close very slowly (they are the "stoners" of the voltage-gated ion channel world)

When NTs bind to an excitatory post-synaptic receptor the net effect is depolarization. What do we call this depolarization and what does it does?

This depolarization is a tiny Excitatory Postsynaptic Potential, a type of graded potential that makes an action potential more likely to occur

Why is propagation via saltatory conduction faster than propagation in nonmyelinated axons of the same diameter?

This is because less charge leaks out through the myelin covered sections of the membrane, more charge arrives at the node adjacent to the active node, and an action potential is generated sooner than if myelin were not present.

Why is the propagation of the action potential from the Axon Hillock to the axon-terminal end typically one-way?

This is because of the absolute refractory period that follows in the "wake" of the moving action potential. Since no new action potentials can be generated in the absolute refractory period, the action potential must continue moving down the axon and cannot change directions

The propagation of action potentials over long distances is possible because of what?

This is possible because of the presence of large local currents which do not degrade over distance

When NTs bind to an excitatory post-synaptic receptor the net effect is either hyperpolarization (if K+ fluxes out) or inhibition of further depolarization (if Cl- fluxes in). What do we call this type of potential and what does it do?

This is refered to as an inhibitory postsynaptic potential (IPSP), which is a graded potential that makes an AP less likely to occur

What is the post-synaptic density?

This is the area on the post-synaptic membrane in which there is a high density of NT receptor proteins

What does it mean to say that action potentials are all or not?

This means that action potentials either occur maximally or they do not occur at all. In other words, there is no variation in the magnitude of action potentials.

What does it mean to say that local current is decremental in a graded potential?

This means that the flow of charge decreases as distance from the site of origin of the graded potential increases

Define threshold stimuli

Threshold stimuli are stimuli that are just strong enough to depolarize the membrane to its threshold potential (-55mV)

Presynaptic Inhibition is one way in which you can modulate chemical synaptic strength. Describe what is occurring in the process. Provide some context before describing the process. What is one important thing to note about this process?

To begin, in presynaptic inhibition, there are 3 neurons rather than just two. We can call these neurons A, B, and C. Neuron B is what we would typically think of as the presynaptic neuron (The "King") and Neuron C is what what we would typically call the post-synaptic neuron (the "Minions"). The 3rd neuron, A can be thought of as an "Advisor to the King," meaning neuron A influences the output of neuron B. In pre-synaptic inhibition, the advisor A secretes NTs which bind to the King, B. This decreases the release of NTs from B to C (King to minions). It is important to note that A can cause B to inhibit BOTH Excitatory and Inhibitory synapses

One way to modulate chemical synapse strength is through the use of neuromodulators. Neuromodulators can interact with receptors on wither presynaptic or postsynaptic cells to modify what?

To modify the effectiveness of the synapse at transmitting a signal

True or false: Graded potentials can be depolarizations or hyperpolarizations

True

True or false: If a voltage-gated sodium channel opens, it will quickly inactivate due to the ball and chain which plugs the poor, preventing the continued flow of sodium

True

True or false: Postsynaptic potentials (IPSPs and EPSPs) are graded, and summation of PSPs allow for neuronal integration at the Axon Hillock (initial segment)

True

True or false: action potentials are dramatic and rapid

True

True or false: an excitatory stimulus will lead to a depolarization first, while an inhibitory stimulus will lead to a hyperpolarization first

True

True or false: graded potentials do not involve changes in the concentration of Na+ or K+

True

True or false: The action potentials resulting from stimuli stronger than those required to reach threshold are exactly the same as threshold stimuli that just barely reach the threshold potential

True: Remember, action potentials are all or none

When NTs bind to an inhibitory post-synaptic receptor. What is the net effect?

Two possible net effects: 1. If, following the bind of the NT to the post-synaptic inhibitory receptor, K+ fluxes out of the cell, the net effect is hyperpolarization 2. If, following the bind of the NT to the post-synaptic inhibitory receptor, Cl- fluxes into the cell, further depolarization is inhibited in both Type 1 (only Cl- leak channels) and Type 2 cells (Cl- leak channels AND active Cl-pumps)

In the process of chemical synaptic transmission, vesicles are constantly fusing with the plasma membrane to promote vesicle exocytosis. What then, stops the cell from running out of intracellular vesicles and prevents the cell membrane from expanding infinitely?

Vesicles are recreated/recycled by endocytosis wherein the cell endocytosizes a portion of the membrane to regenerate intracellular vesicles

Action potentials are associated with what type of ion transport channel?

Voltage-gated ion channel

Describe the speed with which voltage-gated sodium channels open and inactivate

Voltage-gated sodium channels open and inactivate VERY rapidly

In detail, discuss the process by which Ca2+ causes vesicle exocytosis. In your answer, make sure to include the role of synaptotagmin and SNARE proteins

When Ca2+ enters the presynaptic axon terminal, it binds to a protein called synaptotagmin. This binding causes SNARE proteins to attached to the vesicle. By twisting around one another like twisty ties, the SNARE proteins pull the vesicle toward the plasma membrane. Fusion of the vesicle membrane with the lipid bilayer of the cell creates an opening called a fusion pore, out which the NT is released into the synapse.

Multiple sclerosis is caused by destruction of myelin. Describe what this can lead to in terms of symptoms, as well as describing the actual mechanism by which this occurs

When the autoimmune system degrades the myelin sheaths surrounding myelinated axon, it allows for the action potential to dissipate out of the space where the myelin previously was. This can result in slowing of conduction velocity and failure of conduction (i.e. the action potential simply dissipates because there is no longer a barrier keeping the NTs inside the axon)

Place the following processes in chronological order: hyerpolarization, overshoot, repolarization, depolarization

depolarization > overshoot > repolarization > hyperpolarization

Graded potentials are ____________-distance signals that rely only on local flow of ____________ ____________

short; ionic currents