Assignment Task

Part

A. Background

Figure 1 shows a hypothetical neural circuit, consisting of several nerve cells, which have been extracted from the nervous system and grown in a Petri dish. We are recording from four cells: A, B, C and D. These are all simple neurons, with no dendrites. Cell A is a sensory neuron from a dorsal root ganglion. It makes excitatory synapses onto both Cells B and C through the release of glutamate, which acts via fast AMPA-type receptors. The axon between Cell A and Cell B is quite short and thick but the axon between Cell A and Cell C is very long, thin, and tortuous. Cell B makes an excitatory synapse onto Cell D via release of acetylcholine, which acts on nicotinic receptors.

Cell C releases GABA onto GABAA receptors on Cell D giving rise to inhibitory synaptic potentials. Cell D releases glycine as its main transmitter. A microelectrode has been inserted into each of these 4 cells so that we can record membrane potential (A-mV, BmV, C-mV, D-mV), including synaptic potentials and action potentials. A mechanical probe (shown by the pointing hand) is positioned to exert tiny amounts of force on the mechanosensitive endings of Cell A.

On page 3 is a diagram (Figure 2) showing the electrical activity in each of the four cells in millivolts (mV), as recordings of membrane potential (A-mV, B-mV, C-mV, and D-mV), together with a fifth trace which shows the mechanical probing of Cell A in units of force (millinewtons; mN). The recording lasts about 200 milliseconds (ms).

All four cells are initially at their resting membrane potential (RMP) of -68mV (represented by small, dashed lines). Then a tiny force is applied via the probe causing three action potentials to be evoked at the transduction site of Cell A. These action potentials propagate down the axon, past the cell body and into the branching axons to cause EPSPs onto Cells B and C via glutamate acting on AMPA receptors. Cell B fires one action potential; Cell C fires two action potentials. These action potentials in B and C then propagate down their respective axons, releasing acetylcholine from Cell B`s terminal and GABA from Cell C`s terminal, giving rise to a complex waveform of summating synaptic potentials in Cell D.

• Moment where IPSPs temporally summate
• Moment where a Cl- conductance is nearly maximal
• An action potential takes 15ms to move from cell body to terminal
• A force of 90 micronewtons (µN)
• A synaptic potential due to fluxes of both Na+ and K+ through the same channel
• Lower part of rising phase of action potential that is not generated by synaptic input
• Resting membrane potential of a cholinergic neuron
• A voltage-sensitive synaptic potential that is blocked by Mg2+ ions
• Threshold of a nerve cell
• Current flow at an electrical synapse
• An action potential with a large component driven by Cl- ions
• An event with a duration of 23ms
• A synaptic potential mediated by a G-protein coupled receptor
• Moment where an excitatory amino acid is starting to bind to its receptor
• Conduction delay added to synaptic delay
• Resting membrane potential (RMP) of primary afferent neuron
• A long after-hyperpolarisation
• A synaptic potential mediated almost entirely by Ca2+ ions
• Moment where spatial summation occurs
• Moment when most voltage-sensitive Na+ channels are open
• Where temporal summation occurs via release of an excitatory amino acid transmitted
• Where a neuron is firing at a frequency of approximately 140 Hz
• Moment when most voltage-sensitive Na+ channels are inactivated
• After-hyperpolarisation summing with an EPSP
• $overshoot of an action potential
• An after-hyperpolarisation falling below RMP

B. Here, you are required to use your understanding of electrophysiology to predict the effects of a range of drugs, toxins, and ion substitutions on activity in the same circuit as Part A. On page 6, we have printed 8 copies of the same figure, with the original traces from Figure 2 shown in pale orange. Superimposed on each orange original is a solid black trace, showing how a particular drug/toxin/ion substitution has modified the activity of each cell. The relevant effects of each drug are described below – you don’t need to look this up and you shouldn`t add new mechanisms to our list. The tricky bit is that we have shuffled all the A-mV traces. We have also shuffled all the B-mV traces. And C-mV traces and D-mV traces. We haven’t jumbled up different letters (i.e., we haven’t mixed A-mV traces with B-mV traces – we’re not that mean). The aim of this exercise is for you to use your knowledge of neuronal circuit function to determine which traces belong to which drug/toxin/ion substitution.

Questions

1. In Cell A of Figure 2, the top of the first action potential is clearly above the dotted line that marks 0mV. What is the main determinant of how high the action potential rises? A. the resistance of Cell A`s axonal membrane

B. the Na+ equilibrium potential of Cell B

C. the Na+ equilibrium potential of Cell A

D. the resting membrane potential of Cell A

E. the K+ equilibrium potential of Cell A

2. In Cell A of Figure 2, advancing the mechanical probe causes the cell to fire three action potentials. The process of converting physical force into neuronal firing is called:

A. stimulation

B. transformation

C. mechanotransduction

D. frequency coding

E. excitation

3. In Cell A of Figure 2, action potentials arise directly from the resting membrane potential whereas in Cells B and C there is a depolarisation before their action potentials start. Why is Cell A different?

A. Cell A`s action potentials are initiated far away from the cell body

B. Cell A is driven by synaptic potentials that are too small to see on the traces

C. Cell A has all-or-nothing action potentials

D. Cell A is much more excitable than Cells B and C

E. Cell A does not have an after-hyperpolarisation before its action potentials

4. In Cell A of Figure 2, the mechanical probe produces a "generator potential" when it presses on the axonal cell membrane, but this potential is not visible in the trace A-mV. Why not?

A. because the action potentials overwhelm the generator potential

B. because cell body of Cell A lacks dendrites

C. cable properties ensure that the generator potential declines in amplitude between the distant tip of the axon (where the probe is) and the cell body (where the recording was made)

D. because generator potentials are restricted to cell bodies

E. because generator potentials are too small to detect

5. The axon of Cell A that synapses onto Cell C is exactly 3.8mm long. Using data in Figure 2, which is the best estimate of the average conduction velocity of Cell A’s axon between Cell A`s cell body and Cell C? (in metres per second)

A. 0.1 m/s

B. 3 m/s

C. 1 m/s

D. 0.3 m/s E. 10 m/s

6. If a neuron has a firing rate of 40 action potentials per second (i.e., 40Hz), how far apart would be the peaks of adjacent action potentials, on average (in milliseconds)?

A. 100 ms

B. 25 ms

C. 2.5 ms

D. 250 ms E. 10 ms

7. The resistance of a nerve cell body membrane is inversely proportional to:

A. The total number of open K+ channels

B. The surface area of the membrane, irrespective of ion channels

C. The summed conductances of all open ion channels

D. The activity of Na+/K+ ATPase molecules in the cell membrane

E. The total number of ion channels, pumps and exchangers through which ions can move

8. The rising phase of an action potential is usually mostly due to:

A. an outward flux of K+

B. outward flux of Na+

C. inward flux of Na+

D. activity of the Na+/K+ ATPase

E. inward flux of Na+ and K

9. Which of the following would be expected to have the greatest effect on the voltage threshold for an action potential in a neuron?

A. the diameter of its dendrites

B. the density of Cl- channels in the dendrites

C. the density of Ca2+ channels in the nerve terminal

D. the density of K+ channels in the axon terminals

E. the density of voltage-activated Na+ channels in the axon hillock

10. Which of the following is true about presynaptic inhibition?

A. it primarily acts close to transmitter release sites

B. it blocks action potential conduction in axons

C. it increases the threshold of the neuron that receives it

D. it is usually associated with hyperpolarisation of the dendrite or soma

E. it simultaneously affects all synapses onto a neuron

11. The least common mechanism for the removal of transmitter from the synaptic cleft is:

A. diffusion out of the cleft

B. uptake into surrounding cells or nerve terminals

C. spontaneous breakdown of the transmitter molecule

D. oxidation by mitochondria in the synaptic cleft

E. degradative enzymes that break down the transmitter

12. Which of the following is incorrect about the transmitter glycine

A. glycinergic transmission is primarily mediated by increases in Cl- conductance

B. it is an amino acid transmitter

C. it is an abundant transmitter in the central nervous system

D. its receptors are ligand-gated ion channels

E. it has potent excitatory effects

13. Which ion carries most of the current when a GABAA receptor is activated?

A. Cl- ions moving into the cell

B. K+ ions moving into the cell

C. Na+ ions moving out of the cell

D. K+ ions moving out of the cell

E. Cl- ions moving out of the cell