Synaptic Physiology

Question 1

State the Nernst Equation

Answer 1

E = RT/zF ln ([ion outside]/[ion inside]), so for K+, an increase in the ECF concentration would make ln([out]/[in]) less negative and thus the entire E less negative (depolarized).

Question 2

What is an electrical synapse and what is a limitation of this type of synapse?

Answer 2

An electrical synapse has open (gap) junctions between neighboring/synapsing cells that allow direct transmission of electrical impulses. They are limited because they are always excitatory, multiple signals cannot be integrated, and their signal cannot be amplified.

Question 3

Would electrical synapses be useful at NMJs, why or why not?

Answer 3

Electrical synapses would not be useful at NMJs because the signal must be amplified in order to induce an action potential in the muscle cell.

Question 4

Are electrical synapses common or important in the CNS?

Answer 4

No. Electrical synapses are useful in areas where many cells must fire simultaneously, such as the respiratory motor neuron center or in cardiac cells, but not where complex integration of signals is needed (the vast majority of the CNS).

Question 5

What are the three methods available for terminating a NT signal in the synaptic cleft?

Answer 5

Dispersal, degradation, or reabsorption of the NT.

Question 6

What does neostigmine do and what condition is it used to treat?

Answer 6

Neostigmine inhibits Acetylcholine esterase, preventing it from degrading ACh in the synaptic cleft. It is used to treat Myasthenia Gravis by enhancing the signal strength of the NMJ.

Question 7

What is the primary challenge of the neuron at an NMJ?

Answer 7

Every muscle fiber is innervated by a single neuron, but that neuron may innervate many muscle fibers. The neuron must amplify its action potential many times to sufficiently depolarize all of the muscle cells.

Question 8

How does the NMJ neuron successfully depolarize its full group of muscle fibers?

Answer 8

The axon terminal covers a large surface area and releases 2-3 times as much ACh as is needed

Question 9

What is facilitation and how does it occur?

Answer 9

Facilitation is a gradual increase in the strength of a NMJ signal. If the neuron is rapidly fired, Ca++ builds up in the axon terminal faster than it can be eliminated, leading to larger and larger numbers of NT vesicles being released.

Question 10

What is synaptic depression and how does it occur?

Answer 10

Synaptic depression is a gradual loss in strength of signal in the NMJ. It results from frequent firing of the neuron that depletes the neuron’s stores of NT and vesicles.

Question 11

What makes a synapse “fast” or direct?

Answer 11

Direct/Fast synapses are those that contain ligand-gated ion channels on the post-synaptic cell.

Question 12

What makes a synapse “slow” or indirect?

Answer 12

Indirect/Slow synapses are those that contain G-Protein coupled receptors on the post-synaptic cell surface.

Question 13

What is the “reversal potential” of a synapse?

Answer 13

The reversal potential is the average E that an ion channel open to multiple ions (say Na+ and K+ in the case of a Non-Selective Cation channel) is capable of producing.

Question 14

What kind of channels do the ACh receptors in a NMJ synapse link to?

Answer 14

The ion channels in a NMJ synapse are Non-Specific Cation channels and allow both Na+ and K+ to pass through. They have a reversal potential of around -10mV, far more positive than the -50mV necessary to trigger an AP.

Question 15

What kind of channels open during fast inhibition in the CNS?

Answer 15

Chloride channels.

Question 16

Why are inhibitory signals often more powerful than excitatory signals?

Answer 16

Inhibitory signals may induce a negative potential that is only slightly below the resting membrane potential, thus even an infinite number of open channels can only produce a small change in the overall membrane potential. However, an infinite number of inhibitory channels would certainly overwhelm and excitatory signal. Also, inhibitory signals are often received closer to the soma, and exert more influence on the axon hillock by their proximity or by allowing excitatory impulses to disperse.

Question 17

What synaptic condition may coexist with temporal summation?

Answer 17

Temporal summation, the frequent firing of a single neuron, may also induce facilitation.

Question 18

What are the three methods of terminating a synaptic signal?

Answer 18

Diffusion, recycling, and destruction

Question 19

What is the basic structure of an NMDA channel?

Answer 19

NMDA channels are Ca++ channels and are both ligand gated and Mg++ “plugged”. The Mg++ atom is attracted to the negatively charged interior of the cell, and trapped by the ligand gate.

Question 20

How does activation of an NMDA channel strengthen synapses or aid in behavioral associative training?

Answer 20

Activation of NMDA channels requires simultaneous depolarization of the cell and NT binding of the NMDA receptor. Once activated, then NMDA channel allows Ca++ influx, which triggers exocytosis of ligand gated Na+ channels at the synaptic junction. Future signals to the same synapse then induce stronger reactions on the post-synaptic cell.

Question 21

How is the NMDA a “coincidence detector”?

Answer 21

The NMDA channel is only activated by the simultaneous events of ligand binding and cell depolarization, thus it detects the coincidence of these events.

Question 22

Name four examples of electrical synapses.

Answer 22

Respiratory center motor neurons, cardiac cells, retina, and cochlear development.

Question 23

How does botulinum toxin cause damage?

Answer 23

Botulinum toxin is an enzyme that cuts the SNARE proteins in lower motor neurons, preventing the exocytosis of NT at NMJs and resulting in flaccid paralysis.

Question 24

How does tetanus toxin cause damage?

Answer 24

Tetanus toxin is an enzyme that cuts the SNARE proteins in inhibitory inter-neurons, preventing the relaxation of skeletal muscle and resulting in spastic paralysis.

Question 25

What is the “safety factor” at the NMJ?

Answer 25

“Safety factor” refers to the excessive amount of NT released into the NMJ at every AP, ensuring the stimulation of an EPSP.

Question 26

Are safety factors present in CNS synapses? Why or why not?

Answer 26

CNS synapses typically do not have safety factors. This allows for the integration of many sources of information. This integration is necessary for proper neural function. Safety factors would overwhelm the post-synaptic neuron and crowd out competing signals.

Question 27

What is LTP?

Answer 27

LTP is Long Term Potentiation and it reflects the increase in sensitivity of a synapse that has increased its number of NT receptors, (e.g., via the NMDA process).

Question 28

What is LTD?

Answer 28

LTD is Long Term Depression and reflects a decrease in sensitivity of the post-synaptic cell, likely through loss of AMPA receptors. The physiological significance of this is unknown.

Question 29

What is the quantum hypothesis?

Answer 29

The quantum hypothesis states that synaptic triggers occur in discrete quantities, the degree of depolarization occurs in a step-wise manner (not a continuum), individual vesicles may spontaneously release causing tiny depolarizations in the post-synaptic membrane, and that the average vesicle can cause a depolarization of 0.4mV.