Week 1.2 - The Single Neuron & 1.3 - Lab Visit

Question 1

What are the four functional regions of the neuron. Name the structure corresponding to these region in a typical neuron.

Answer 1

Most neurons, regardless of type, have four functional regions in which different types of signals are generated.

Input: dendrites;
integration: soma/axon hillock;
conductive: axon;
output synapses/axon terminals

Question 2

There are about 10¹¹ neurons in the brain, and between 10¹⁴ and 10¹⁵ synapses in the brain, how many synapses do we have per neuron?

Answer 2

about 5000 (!) synapses per neuron

Question 3

At which point in the neuron is an action potential initiated? Why?

Answer 3

Action potentials, or spikes are initiated at the axon initial segment (AIS); which is also called trigger zone. Large concentration of Sodium Channels

Question 4

What is a synapse?

Answer 4

A synapse is a specialized structure allowing communications between neurons or a neuron with another cell.

Question 5

As the intensity of an input stimulus increases, the ______ of the action potentials increases as well.

Answer 5

firing rate / spike rate / firing frequency

For a given neuron, the size of the action potential is always the same. The frequency of the action potentials can change however.

Neurons can encode the stimulus strength as spike rate. This is kind of coding scheme is known as rate-coding.

Question 6

What is the membrane potential (V_m) ?

Answer 6

a potential that results from a separation of charge across the cell membrane (voltage). In other words, it is the difference in electric potential between the interior and the exterior of a biological cell.

Question 7

What makes a neuron an “excitable cell”?

Answer 7

The presence of voltage-gated ion channels makes a neuron an excitable cell. The term excitable refers to the ability of some cells to be electrically excited resulting in the generation of action potentials. Neurons, muscle cells (skeletal, cardiac, and smooth), and some endocrine cells (e.g., insulin-releasing pancreatic β cells) are excitable cells.

https://www.physiologyweb.com/glossary/e/excitable_cell.html

Question 8

What is the Nernst equation and what does it calculate?

Answer 8

With the Nernst equation you can calculate the equilibrium potential for a given ion.

Remember that the [square brackets] represent concentration and R, T, z and F are all constants; T is the absolute temperature; z is the valency of the ion.

Question 9

How can we calculate the membrane potential (V_m) in real cells with multiple ion channels in its membrane?

Answer 9

When more than one ion channel is present in the membrane, the membrane potential can be calculated by using the Goldman-Hodgkin-Katz equation (GHK equation). Usually, only K⁺, Na⁺, and Cl^- are implemented;

* the larger P is, the more it contributes to the membrane potential.

Question 10

Which two fundamental processes are at play in establishing the equilibrium/Nernst potential (V_eq) of an ion across a membrane?

Answer 10

The equilibrium/Nersnst potential (V_eq) is the voltage at the point where the chemical gradient (as result of ion type distribution) the and the electrical gradient (+/-) cancel each other out and are thus, in balance.

Question 11

What is so special about an ion?

Answer 11

Ions are atoms with a charge. There are cations (+) and anions (-).

Question 12

By what 2 factors is the membrane potential (V_m) established?

Answer 12

• The asymmetric distribution of ions across the plasma membrane (ion concentration gradients)
• The selective permeability of different ions by the plasma membrane (ion channels).

Question 13

What is the value of the resting membrane potential (V_rest) in a typical neuron?

Answer 13

The value of the resting membrane potential varies from cell to cell, from about −20 mV to −100 mV.
But typically we use -70mV

Question 14

What is the main difference between passive ion channels and active ion channels?

Answer 14

Passive channels, also called leakage channels, randomly switch between an open and closed state or stay open at all times.

An active channel is a channel that can open or close in responds to changes in the environment. Voltage-gated channels open and close in response to changes in membrane potential. Ligand-gated channels open and close in response to the presence of a molecule (ligand).

Question 15

Looking at the Nernst equation, which factors have a significant impact in determining the outcome?

Answer 15

Specifically;

(1) the concentration gradients, (2) the valence of the ionic species in question, and (3) temperature.

Question 16

The AP is the core mechanism that allows the neuron to do its job, which is receiving and propagating ______

Answer 16

information

Question 17

Describe each stage of an action potential in the image

Answer 17

0. Neuron at its resting membrane potential.
1. Depolarisation. Is the result from the Na+ channels that open, leading to an influx of the positively charged Na+ ions. This leads to the inside of the cell becoming more and more positive (relative to the outside).
2. Overshoot. Here, the membrane potential becomes positive.
3. Peak. At this point, p_Na​ is 600x greater than at its resting value.

V_m​ is close to V_Na​, though never reaches it because…

• The Voltage gated Na+ channels begin to inactivate rapidly after they open.
• Neurons have Voltage gated K+ channels that become activated by membrane depolarisation as well, but they just open much slower. That is why these channels are called delayed rectifiers, at the peak the P_K is greater than at rest.

4. Repolarisation. The outflux of K+ causes the inside of the cell to become more negative again, back to its resting value.
5. Hyperpolarisation. When the resting potential is reached, the K+ do not immediately close again (they are slow). Leading the membrane potential to become a bit more negative before it will return to its resting value.

Question 18

How can you interpret the following graph? (focus on the green and red line)

Answer 18

Note that:

• These are the Na+ and K+ conductances (g) respectively, which has to do with the opening and closing of the selective ion channels of Na+ and K+.
  
  • The line of Na+ has an early peak and quickly decays after that, while the K+ conductance rises slower but also decays slower. After the peak, the conductance of K+ is higher than Na+ .

Question 19

What is the absolute refractory period?

Answer 19

This is a period in right after the action potential in which it is impossible to fire another action potential, no matter how strong the stimulus.

Question 20

Biological membranes act in similar ways as ________ because it ______ charges

Answer 20

capacitors

stores

* A capacitor is a device that allows separation of electrical charge, so an electric field is established (meaning voltage) across its plates.

Question 21

What is the difference between an ion channel and a transporter/pump?

Answer 21

Ion channels are pores in the cell membrane that passively transport ions from one side to the other.

Ion transporters perform active transport by moving ions against their concentration gradient. The channels need energy (ATP) to do this.

Question 22

A) Name the 3 main families of ion channels.

B) Of what type are the K+ and Na+ channels that are involved in generating an action potential?

Answer 22

A)

1. Ligand-gated
2. Gap junctions
3. Voltage-gated

B)

These are Voltage Gated channels. Their gates open at a specific voltage.

Question 23

Name the technique used to study single ion channels.

Answer 23

The Patch clamp technique allows high-resolution current recordings for a specific patch of membrane. That is useful because now scientists can focus on just a few ion channels at a time.

General procedure

A glass pipette containing electrolyte solution is tightly sealed onto the cell membrane and thus isolates a membrane patch electrically. Currents fluxing through the channels in this patch flow into the pipette and can be recorded by an electrode that is connected to a highly sensitive differential amplifier. In the voltage-clamp configuration, a current is injected into the cell via a negative feedback loop to compensate changes in membrane potential. Recording this current allows conclusions about the membrane conductance.

Question 24

What is the relative refractory period?

Answer 24

A period after the absolute refractory period, in which it is more difficult to trigger another action potential. Meaning a stronger stimulus is needed.

Question 25

What causes the refractory period of an action potential?

Answer 25

1. Many voltage-gated Na⁺ channels are still inactivated.
2. Many voltage-gated K⁺ are still open.

Question 26

Why is the voltage clamp important for studying voltage-gated ion channels?

Answer 26

By controlling the membrane potential, it allows the study of how these open and closes in response to membrane potential.

Question 27

The Hodgkin-Huxley model is a four dimensional model. Which are the four variables and what do they represent?

Answer 27

V: membrane potential

n: gating variable of K+ channel, represents activation

m: gating variable of Na+ channel, represents activation

h: gating variable of Na+ channel, represents inactivation

Question 28

Which are the three conductances (g) present in the Hodgkin Huxley model? What do they represent?

Answer 28

g_K: K+ conductance. Voltage-gated K+ channels

g_Na: Na+ conductance. Voltage-gated Na+ channels

g_l: leak conductance. All other passive ion-channels.

Question 29

What would happen to E_K if we increase intracellular [K⁺]?

Answer 29

E_K becomes more negative

(test it!)

Question 30

What would happen to E_K if we increase extracellular [K⁺]?

Answer 30

E_K becomes more positive.

Question 31

What would happen to E_Cl if we increase intracellular [Cl^-]?

Answer 31

E_Cl becomes more positive. (why?)

Question 32

What would happen to resting membrane potential (V_rest) of a neuron if we increase extracellular [K⁺]?

Answer 32

The neuron will be depolarized as E_K becomes more positive and the cell membrane is most permeable to K⁺ at rest.

It may even start firing action potentials if the depolarization is large enough.

Question 33

What would happen to resting membrane potential of a neuron if we decrease extracellular [Na⁺]?

Answer 33

Although E_Na becomes more negative, the neuron will be not be affected much as the cell membrane is not very permeable to Na⁺ at rest.

Question 34

What would happen to excitability of a neuron if we decrease extracellular [Na⁺]?

Answer 34

E_Na becomes more negative. It may decrease the ability of a neuron to fire action potential.

Question 35

What can we learn from the reversal potential of an ion channel?

Answer 35

We can know whether the effect of opening this channel will be depolarizing or hyperpolarizing.

We may guess at what ions it is permeable to.

Question 36

Which part of a neuron is responsible for its input?

Answer 36

It’s Dendrites

Question 37

Which part of a neuron is responsible for its output?

Answer 37

The Axon

Question 38

Which scientist duo studied the squid giant axon in the 1950s?

Answer 38

Hodgkin and Huxley

Question 39

Which ion channel(s) is/are responsible for the generation of action potentials?

Answer 39

The Sodium and Potassium channels

Question 40

Which ion channel is blocked by tetrodotoxin (TTX)?

Answer 40

Sodium channel

Question 41

Which ion channel is blocked by tetraethyl ammonium (TEA)?

Answer 41

Potassium channel

Question 42

Which scientist duo studied invented the patch clamp technique?

Answer 42

Neher and Sakmann

Question 43

Explain what is depicted in this diagram.

Answer 43

Neural activity is often displayed with a raster plot. Raster plots are all about firing rates, where each line in the plot represents one spike. Each row of spikes is called a spike train and represents the activity of the neuron for a specific time interval, here 1500 ms (or 1.5 seconds). The average firing rate is called the baseline firing rate of a neuron, which is given in Hz (Hertz). Recall that Hz is the unit for frequency, given by 𝑓=𝜆𝑣. Where 𝜆 is the wavelength and 𝑣 velocity.

For this particular recording the baseline firing rate is 6Hz, meaning the neuron on average fires 6 spikes per second when no stimulus is presented (we get that by taking the average of lines of all neurons before the blue line). When a stimulus is presented, marked by the blue line, you see that there are much more lines! Now the neuron fires on average 30 spikes per second (30Hz).