NBL Module 7

Synaptic Transmission

Neurons communicate through electrical signaling, with synaptic transmission involving the production of small graded potentials (EPSPs or IPSPs) on the postsynaptic side.

Graded Potentials

Small, non-regenerative changes in membrane potential resulting from synaptic inputs, which can be excitatory or inhibitory and summate within the cell body.

Action Potential

Large, regenerative changes in membrane potential for long-distance signaling, conducted along the axon from the cell body to the synapse.

Initial Segment

Region of the axon where the action potential is generated before being propagated along the axon to the presynaptic terminus.

Resting Membrane Potential

Membrane potential maintained by active transporters and leak channels, crucial for signaling and molecule transport in cells.

Edgar Adrian

Scientist who recorded the first action potentials in the early 20th century, demonstrating the all-or-none nature and stimulus intensity relationship of action potentials.

Axon Function

Involves generating and conducting action potentials from the initial segment to the presynaptic region for neurotransmitter release, essential for synaptic transmission.

Action Potential

A transient change in the membrane potential of a neuron, characterized by a depolarization followed by repolarization and hyperpolarization.

Summation

The process by which excitatory and inhibitory inputs on a neuron's membrane potential combine to reach a threshold for generating an action potential.

Threshold

The membrane potential level (-55 millivolts) at the initial segment of the axon hillock that must be reached to trigger an action potential.

All-or-None Response

Once the threshold is met, the action potential is initiated in a neuron, leading to a consistent depolarization and repolarization.

Excitable Cells

Neurons and muscle cells are excitable cells capable of generating action potentials due to the expression of specific ion channels like voltage-gated sodium and potassium channels.

Neural Code

Information in neurons is encoded not in a single action potential but in the frequency and pattern of action potentials, crucial for communication between neurons.

Hodgkin and Huxley

Scientists who discovered the ionic basis of the action potential in the 1930s and 1940s, using the squid giant axon as a model system.

Rising Phase

Part of the action potential where there is an inward current due to the activation of sodium channels, leading to depolarization.

Falling Phase

The repolarization phase of the action potential where there is an outward flow of positive ions, primarily potassium ions, returning the membrane potential to its resting state.

Undershoot Phase

Following repolarization, a brief hyperpolarization phase occurs due to additional outward positive ions moving out of the cell before returning to the resting membrane potential.

Neurons receive inputs from ________ axon(s).

Thousands of

One excitatory and one inhibitory

Tens of

Millions of

Thousands of

EPSPs and IPSPs are types of _____ potentials

End plate

Action

Resting membrane

Receptor

Graded/electrotonic

Graded/electrotonic

The action potential evolved _____.

To overcome the problem of passive decay of membrane potentials

For signaling along the axon

For long distance electrical signaling

All of these answers

So that neurons can communicate with targets that are far away

All of these answers

Which of the following IS NOT a typical function of the axon?

Generate action potentials at the initial segment

Conduct action potentials along the length

Initiate synaptic transmission at the presynaptic terminus

Generate and summate graded potentials at the Nodes of Ranvier

Generate and summate graded potentials at the Nodes of Ranvier

Which of the following BEST DESCRIBES the action potential (AP)?

An AP is all-or-none

In most neurons, if many EPSPs are received, APs can be generated in the axon, cell body and dendrites

For a given neuron, the AP varies in magnitude and time course

APs typically fire once every 10 seconds (0.1Hz)

All neurons fire AP

An AP is all-or-none

What distinguishes an action potential (AP) from other membrane potentials?

The AP is always a large depolarization followed by a repolarization of the membrane potential

The AP typically occurs in the axon

All of these answers

The AP is regenerating

The AP is all-or-none

All of these answers

All cells can produce action potentials but only neurons and muscles use action potentials for signaling. 

True

False

False

Hodgekin and Huxley used the two electrode system to _______the action potential.

measure the changes in membrane potential during

investigate the conductances underlying

Correct!

all of these answers

identify the currents underlying

characterize the phases of

Hodgekin and Huxley used the two electrode system to _______the action potential.

Measure the changes in membrane potential during

Investigate the conductances underlying

All of these answers

Identify the currents underlying

Characterize the phases of

All of these answers

The addition/subtraction of all the ______ is called summation in neurons.

Nernst potentials

Action potentials

Ionic gradients in the neuron

All of these answers

Synaptic EPSPs and IPSPs

Synaptic EPSPs and IPSPs

Summation takes place_______.

In the dendrites

At the presynaptic region

In the cell body at the axon hillock

At all membranes in the neuron

At the initial segment of the axon

At all membranes in the neuron

In a neuron, threshold for firing an action potential depends on the ______.

Fast negative cycle of the action potential

All of these answers

Localization of the voltage gated K+ channels

Inactivation of the voltage gated Na+ channels

Density and voltage sensitivity of the voltage gated Na+ channels

Density and voltage sensitivity of the voltage gated Na+ channels

The action potential is generated at the ______ of the axon hillock. 

Trigger zone/initial segment

The reason the action potential is generated in that specific region of the axon hillock is because it is the region where _____.

Excitatory synapses are densest

All of these answers

Summation is greatest

The resting membrane potential is more depolarized

Voltage gated Na+ channels are first localized along the axon

Voltage gated Na+ channels are first localized along the axon

The currents that underlie the action potential are________.

An inward Na+ current followed by an inward K+ current

An outward Na+ current followed by an outward K+ current

An inward Na+ current followed by an outward K+ current

An inward Na+ current followed by an inward Na+ current

All of these answers

An inward Na+ current followed by an outward K+ current

In the action potential (AP) the membrane potential depolarizes a total of about_____ mV to the peak, then repolarizes with a total time course of the AP of approximately _____.

1 V, 40 msec

10 mV, 0.4 msec

1 mV, 0.04 msec

100 V, 4 sec

100 mV, 4 msec

100 mV, 4 msec

Match the phase of the action potential with the change in the membrane potential.

Rising phase

Falling phase

Undershoot

Threshold

Depolarization

Repolarization

Hyperpolarization

Depolarization

Match the phase of the action potential with the underlying mechanism.

Rising phase

Reaching threshold

Falling phase

Undershoot

Activation

Voltage gated Na+ channels

Summation of EPSPs & IPSPs

Voltage gated K+ channels

Voltage gated K+ channels and other K+ channels

Voltage gated Na+ channels

Which of the following BEST DESCRIBES voltage gated Na+channels?

They contain twelve voltage sensor transmembrane spanning domains (12 S4 domains) in each protein

They are selective for only Na+, and facilitate the transmembrane Na+ current

They are localized to the initial segment but not along the rest of the axon

They are expressed in all cells

All of these answers

They are selective for only Na+, and facilitate the transmembrane Na+ current

The S4 domains of voltage gated channels are the voltage sensors that ______.

Allow the Na+ and K+ channels to interact with each other

Form the ion channel/pore region

All of these answers

Form the inactivation segment/gate that binds to the channel pore region

Are transmembrane spanning domains containing positive amino acids and move when threshold is reached

Are transmembrane spanning domains containing positive amino acids and move when threshold is reached

After inactivation, the closed-inactive voltage gated Na+ channels require that ________ to return to the closed-active state,

They initially reverse to the active-open state before closing again

The membrane potential reaches the Nernst potential for K+ (-84 mV)

The voltage-gated K+ channels close

The membrane potential repolarizes close to the resting membrane potential

All of these answers

The membrane potential repolarizes close to the resting membrane potential

In the ______ cycle of the action potential, activation of VG Na+ channels leads to an inward Na+ current, which further depolarizes the membrane potential, which activates nearby VG Na+ channels.

Rapid influx

Fast positive

Regeneration

Slow efflux

Slow negative

Fast positive

Which of the following BEST DESCRIBES voltage gated K+channels?

They can exist in three states, closed-active, open and closed-inactive

They activate/open at the same rate as the voltage gated Na+ channels

They enhance the depolarization phase of the AP

They contain a single protein with 12 transmembrane spanning domains and 4 S4 voltage sensor regions

They contribute significantly to the relative refractory period of the AP

They contribute significantly to the relative refractory period of the AP

When the drug lidocaine or novocaine is applied to the skin or muscle, it will _______in that region.

Block action potential generation and conduction

Enhance the rate of action potential conduction

Have no effect on action potentials

Decrease both the absolute and relative refractory periods

Lead to an increase in the frequency of action potentials

Block action potential generation and conduction

As the action potential proceeds from the resting membrane potential of -67 mV to the peak of +30 mV, the driving force for Na+ ___ and the driving force for K+ ____.

Increases, increases

Decreases, decreases

Decreases, increases

Stays the same, stays the same

Increases, decreases

Decreases, increases

If both voltage gated Na+ channels and voltage gated K+ channels activated and opened at exactly the same time, the peak of the action potential would be close to ______.

+60 mV

-67 mV

+30 mV

-84 mV

0 mV

0 mV

If the voltage gated Na+ channels didn't inactivate, the membrane potential would initially depolarize_______.

To a value between +30 and +60 mV and then slowly repolarize to about 0 mV

To 0 mV and depolarize slowly to +60 mV

To a value between +30 and +60 mV and then rapidly repolarize to the resting membrane potential

To +60 mV and remain at +60 mV

To a value between +30 and +60 mV and remain at the same level

To a value between +30 and +60 mV and then slowly repolarize to about 0 mV

If there were twice as many voltage gated K+ channels, the action potential would ______.

Depolarize more slowly

Repolarize more rapidly

Repolarize more slowly

Not be affected

Depolarize more rapidly

Repolarize more rapidly

The absolute refractory period depends on ______.

Inactivation of voltage gated Na+ channels

The summed membrane potential at the initial segment

The time constant and length constant

All of these answers

Threshold

Inactivation of voltage gated Na+ channels

The absolute refractory period determines ______.

That only one action potential can be conducted along the axon at one time

All of these answers

That the voltage gated K+ channels will close

That the action potential travels in one direction toward the axon terminus and presynaptic region

The theoretical maximal rate of action potentials at 1 AP/sec or 1 hz

That the action potential travels in one direction toward the axon terminus and presynaptic region

The relative refractory period depends on ______.

All of these answers

The voltage gated Na+ channels and rate of depolarization of the membrane potential

Both voltage gated Na+ and K+ channels and their rate of inactivation

Both voltage gated Na+ and K+ channels and rate of action potential conduction

The voltage gated K+ and other K+ channels and rate of repolarization of the membrane potential

The voltage gated K+ and other K+ channels and rate of repolarization of the membrane potential

The relative refractory period helps to determine _______.

All of these answers

The rate of voltage gated K+ channel activation

How quickly a subsequent AP can be generated and thus the AP frequency

The rate of AP conduction along the axon

Whether the current will be transmembrane or axial

How quickly a subsequent AP can be generated and thus the AP frequency

A single action potential is limited since it ____.

It is so rapid, peaking at about 1 msec

It is triggered at the initial segment

It can't reflect the amount of summed graded potentials that produced

Is a transient change in the membrane potential

It can't reflect the amount of summed graded potentials that produced

Neurons typically receive EPSPs and IPSPs from ______ synaptic input(s).

One

Thousands of

Dozens of

A few

Millions of

Thousands of

For the majority of neurons, which of the following IS NOT an important function of the axon?

Integrate (add/subtract) synaptic potentials and action potentials

Provide fast axonal transport for the movement of cargoes to and from the presynaptic region

Produce action potentials when the membrane potential is depolarized beyond threshold

Conduct/propagate action potentials along the length of the axon to the presynaptic region

Activate synaptic transmission at the presynaptic region

Integrate (add/subtract) synaptic potentials and action potentials

Which of the following is NOT TRUE about the action potential (AP)?

APs are similar in magnitude and time course but can vary slightly in the peak, shape, and length

APs are generated once every second (1 Hz) in an action potential train

APs are large regenerating electrical signals

AP rate/frequence can encode information about the inputs that a neuron receives

APs are generated at the initial segment of the axon

APs are generated once every second (1 Hz) in an action potential train

Only neurons and muscle cells can produce action potentials, which they use for signaling.

True

False

True

Neurons evolved action potentials to overcome _________.

The changes in driving forces during graded potentials

How slowly graded potentials change

Passive decay of graded potentials

All of these answers

The differences between short and long axons

Passive decay of graded potentials

_____________ refers to the addition/subtraction of all the graded potentials in an interneuron.

Translation

Threshold

Derivation

Generation

Summation

Summation

The place in the neuron where the addition/subtraction of graded potentials occurs is ___________.

Everywhere in the neuron

At the initial segment of the axon

At the postsynaptic regions of dendritic spines

In the dendrites

In the presynaptic region of the axon

Everywhere in the neuron

The action potential is generated at a specific region of the neuron because this is the _______.

only region where graded potentials are generated

First region in the axon where voltage gated Na+ and K+ channels are localized

Only place in the neuron where threshold is reached

Area of the axon hillock where EPSPs and IPSPs are largest

All of these answers

First region in the axon where voltage gated Na+ and K+ channels are localized

All of the following affect threshold for generating an action potential EXCEPT ___________.

The fast positive cycle of the action potential

The diameter and length of an axon

The voltage sensitivity of voltage gated Na+ channels

The gene expression of voltage gated Na+ channels

The localization and density of voltage gated Na+ channels

The diameter and length of an axon

During the action potential, all of the following change EXCEPT _________.

The ion conductances

The membrane potential

The ion concentration gradients

The ion currents

The ion driving forces

The ion concentration gradients

Match the phase of the action potential with the underlying mechanism.

Reaching threshold

Rising phase

Falling phase

Undershoot

Resting membrane potential before and at the end of the AP

Graded potential addition/subtraction

Voltage gated Na+ channels are open

Voltage gated Na+ channels are inactivated; voltage gated K+ channels are open

Some voltage gated K+ channels and Ca2+ activated K+ channels are open

Only leak channels are open

Which of the following is NOT TRUE about voltage gated Na+ channels (VGNa+C)?

VGNa+C are expressed in the majority of cells

VGNa+C are localized to the initial segment and along the length of the axon

VGNa+C are activated by depolarization of the membrane potential above threshold (-55 mV)

VGNa+C are formed by a protein with 24 transmembrane spanning domains, with 4 voltage sensor S4 domains

VGNa+C contain a built-in inactivation mechanism, the inactivation segment/gate that can bind to and block the cytoplasmic region of the channel

VGNa+C are expressed in the majority of cells

Which of the following is NOT TRUE about most voltage gated K+ channels (VGK+C)?

VGK+C are localized to the initial segment and along the length of the axon

VGK+Cs can exist in two states: closed or open

VGK+Cs contribute to both the depolarization and repolarization of the AP

VGK+Cs are formed by 4 subunit proteins with 6 transmembrane spanning domains, with a voltage sensor (S4) domain in each subunit

VGK+Cs activate/open more slowly than voltage gated Na+ channels

VGK+Cs contribute to both the depolarization and repolarization of the AP

Which of the following is NOT TRUE about the voltage sensor (S4) domains?

Voltage sensor domains are located in the cytoplasmic loops

Voltage sensor domains are alpha helices that contain numerous basic/positively charged amino acids

Voltage sensor domains are transmembrane spanning domains

Voltage sensor domains undergo a conformational change in response to depolarization of the membrane potential

Voltage sensor domains undergo a conformation change that leads to opening of the ion channel pore region

Voltage sensor domains are located in the cytoplasmic loops

In order to return to the closed-active state, both voltage gated Na+ channels and voltage gated K+ channels require that _________.

The channels first inactivate

The membrane potential subsequently reaches the Nernst potential for K+

All of these answers

The membrane potential first reaches the Nernst potential for Na+

The membrane potential repolarizes to the resting membrane potential

The membrane potential repolarizes to the resting membrane potential

The currents that underlie the action potential are ________.

An inward/negative Na+ current followed by an outward/positive K+ current

An outward/positive Na+ current followed by an outward/positive K+ current

An inward/negative Na+ current followed by an inward/negative K+ current

An outward/positive Na+ current followed by an inward/positive K+ current

An inward/negative Na+ current followed by an outward/positive K+ current

Which of the following is NOT TRUE about the driving forces for Na+ and K+ during the action potential (AP)?

The DFs for Na+ and K+ reverse signs during the course of the AP

At about -10 mV, the DF for Na+ and K+ are approximately equal in magnitude

At the peak of the AP, the magnitude of the DF for K+ is larger than the DF for Na+

The DFs for Na+ and K+ depend on the membrane potential during the AP

At the beginning and end of the AP, the magnitude of the DF for Na+ is larger than the DF for K+

The DFs for Na+ and K+ reverse signs during the course of the AP

The reason that the peak of the action potential can never be more than +60 mV is because of ______.

The driving force for Na+

All of these answers

The Nernst potential for Na+

The inactivation of the VGNa+C

The NA+/K+ ATPase and the gradient for Na+

All of these answers

Application of the drug lidocaine or novocaine to the skin or muscle would _______ in that region.

Decrease both the absolute and relative refractory periods

Block action potential generation and conduction

Have no effect on action potentials

Lead to an increase in the frequency of action potentials

Enhance the rate of action potential conduction

Block action potential generation and conduction

Tetrodotoxin is a protective toxin in puffer fish that binds to and blocks _________.

Gated ion channels

Voltage gated K+ channels

Voltage gated Na+ and voltage gated K+ channels

Leak ion channels

Voltage gated Na+ channels

Voltage gated Na+ channels

Which of the following is NOT TRUE about the relative refractory period? AP = action potential

It is the time period after the peak of the AP and the end of the AP when the membrane potential returns to the resting membrane potential

It can affect how rapidly the next AP can be generated

It can be different for different neurons

It depends on voltage gated K+ channels and other K+ channels

It depends on the magnitude of the AP

It depends on the magnitude of the AP

Which of the following is NOT TRUE about the absolute refractory period?

It is the period during which a subsequent AP cannot be generated

It determines the direction of conduction of the AP from the cell soma to the presynaptic region

It depends on the inactivation of VGNa+C

It is typically 3-5 msec in duration

It determines the theoretical maximal rate of AP firing

It is typically 3-5 msec in duration

You’ve discovered a population of neurons that express mutant VGNa+Cs that inactivate twice as SLOWLY as normal. You record Action Potentials from these neurons and observe that the membrane potential depolarizes _________.

To between 0 and +30 mV and then repolarize to the RMP

To about 0 mV and then repolarize to the RMP

To about +30 mV and remain at +30 MV

And repolarize similar to the normal neurons

To between +30 and +60 mV and then repolarize to the RMP

To between +30 and +60 mV and then repolarize to the RMP

You’ve discovered a population of neurons that express mutant VGNa+Cs that inactivate twice as FAST as normal. You record Action Potentials from these neurons and observe that the membrane potential depolarizes _________.

To between 0 and +30 mV and then repolarize to the RMP

To about 0 mV and then repolarize to the RMP

To about +30 mV and remain at +30 MV

And repolarize similar to the normal neurons

To between +30 and +60 mV and then repolarize to the RMP

To between 0 and +30 mV and then repolarize to the RMP

You’ve discovered a population of neurons that express mutant VGNa+Cs that don’t inactivate. You record action potentials (APs) from these neurons and observe that the membrane potential depolarizes to _______.

Depolarizes to about 0 mV and then remains at 0 mV

And repolarizes similar to normal neurons

Depolarizes to about +60 mV and then repolarizes to the RMP

Depolarizes to about 0 mV and repolarizes to the RMP

Between +30 and +60 mV and then repolarizes to about 0 mV

Between +30 and +60 mV and then repolarizes to about 0 mV

You’ve discovered a population of neurons that expresses only 25% as many voltage gated Na+ channels as normal. You record action potentials from these neurons and observe that ________ compared to the normal neurons?

These neurons require more inputs to activate an AP

Threshold for firing an AP is more positive/less negative

These neurons are less excitable

All of these answers

The peak of the AP is lower

All of these answers

You’ve discovered a population of neurons that express twice as many VGK+Cs than normal. You record Action potentials from these neurons and observe that the membrane potential _________ than in normal neurons.

Repolarizes more rapidly

Repolarizes more slowly

Depolarizes more slowly

Depolarizes more rapidly

Is larger and longer lasting

Repolarizes more rapidly

You’ve discovered a population of neurons that express twice as many VGK+Cs than normal. What effect would this have on the refractory periods?

It would decrease the absolute refractory period.

It would increase the relative refractory period.

It would decrease the relative refractory period.

It would increase the absolute refractory period.

It would have no effect on the refractory periods.

It would decrease the relative refractory period.

You’ve discovered a population of neurons that express half as many VGK+Cs than normal. What effect would this have on the refractory periods?

It would decrease the absolute refractory period.

It would increase the relative refractory period.

It would decrease the relative refractory period.

It would increase the absolute refractory period.

It would have no effect on the refractory periods.

It would increase the relative refractory period.

You’ve discovered a population of neurons in which the VGNA+Cs and VGK+Cs activate at exactly the same rate. In these neurons, the membrane potential would ________.

Depolarize to about +30 mV and remain at +30 mV

Remain at the RMP (an AP would not be generated)

Depolarize to about +60 mV and repolarize to the RMP

Depolarize to between +30 mV and +60 mV and then repolarize to 0 mV

Depolarize to about 0 mV and then repolarize to the RMP

Depolarize to about 0 mV and then repolarize to the RMP

In evolving the action potential with the characteristics that it has, neurons encountered one major problem, which is that an individual action potential _________.

Can’t be propagated along the axon continuously

All of these answers

Can’t provide information about how much activity produced it

Is too transient to transmit information

Is too small to consistently activate synaptic transmission

Can’t provide information about how much activity produced it

Once the AP has finally returned to the resting membrane potential at the end of the AP, what happens if the neuron at the initial segment of the axon hillock is immediately depolarized above threshold?

The voltage gated K+ channels are open so an AP will not be generated

A subsequent AP will be generated and the magnitude of the AP will be larger

The voltage gated Na+ channels are inactivated so an AP will not be generated

A subsequent AP will be generated but the magnitude of the AP will be similar

A subsequent AP will be generated with a similar magnitude to the initial one

A subsequent AP will be generated with a similar magnitude to the initial one

The fast positive cycle AND slow negative cycle of the action potential involve ______.

Activation of voltage gated Na+ and K+ channels

Changes in conductance of the voltage gated Na+ and K+ channels

All of these answers

Changes in the membrane potential

Changes in the Na+ current and K+ current

All of these answers

_________________ is a non-invasive form of brain stimulation used to produce electric current at a specific brain region.

X-ray stimulation

All of these answers

Electroencephalography (EEG)

Transcranial Magnetic Stimulation (TMS)

Functional magnetic resonance imaging (fMRI)

Transcranial Magnetic Stimulation (TMS)