Presynaptic Inhibition

Question 1

Role of the Na+/K+ ATPase pump

Answer 1

Actively pump three Na+ out and K+ into the cell
Depolarised internal environment

Question 2

Two types of channels

Answer 2

Voltage gated
Leak

Question 3

Role of the sodium channel

Answer 3

Rapid influx of sodium into the cell upon opening resulting in depolarisation

Question 4

Role of potassium channels

Answer 4

Permits rapid efflux of potassium out of the cell causing hyperpolarisation

Question 5

What is the resting membrane potential

Answer 5

-70mV

Question 6

What two forces do ions act under

Answer 6

Electrostatic force (depends on charge)
Force of diffusion (concentration)

Question 7

Action potential steps

Answer 7

1) resting membrane potential
2) depolarisation stimuli via graded potential
3) depolarisation reaches threshold NaV open and sodium ions enter (VGSC open at the axon hillock)
4) rapid Na+ entry further depolarises the neuron
5) Nav channels inactivate and slower potassium (0.5ms) Kv channels open
6) potassium ions move out of neuron, it becomes negative
7) Kv channels remain open, more potassium leaves neurons causing hyperpolarisation
8) Kv channels close, some potassium ions enter via leak channels
9) normal resting membrane potential

Question 8

Synaptic transmission

Answer 8

AP arrives
VGCC open
Calcium ion influx
Vesicles bind to post synaptic membrane
Exocytosis of vesicles
NT diffuses across synaptic cleft and activates post synaptic cell

Question 9

What does more APs cause

Answer 9

More NT release

Question 10

Excitatory and inhibitory inputs on the post synaptic neuron

Answer 10

Excitatory - neuron depolarises
Inhibitory - neuron is hyperpolarised and decreases the firing potential

In reality - combination of both

Question 11

Graded potential

Answer 11

Not all or nothing (stronger stimulus correlates to a larger change in membrane potential)
Rapid decay
Post synaptic channel opens, membrane potential spread through cytoplasm and diminishes over time (ripple effect)

Question 12

Triggering an AP in the postsynaptic cell

Answer 12

Channels of postsynaptic cell open causing depolarisation
Depolarisation travels to the AIS (densely packed VGSC population)
Depolarisation needs to reach threshold to generate an AP
If threshold reached - all or nothing AP

Question 13

Spatial summation

Answer 13

Multiple inputs from presynaptic neurons synchronously summate to trigger an AP

Question 14

Temporal summation

Answer 14

Multiple signals synchronously fire and summate to cause an AP

Question 15

Normal functioning synaptic modulation

Answer 15

1. Excitatory neuron fires (glutamate)
2. AP is generated
3. Signal is passed to all targets
4. Postsynaptic response is initiated

Question 16

Steps in presynaptic inhibition

Answer 16

1) An excitatory neuron fires
2) a graded EPSP causes AP
3) inhibitory neuron fires preventing NT release at 1 synapse (giving rise to a hyper polarising current)
4) postsynaptic response in the rest of the synapses

Question 17

Steps in postsynaptic inhibition

Answer 17

1) both an excitatory and inhibitory neuron fire
2) below threshold graded potential
3) no AP generated
4) no response elicited at any target

Question 18

What does presynaptic inhibition cause

Answer 18

More specific control
Precise inhibition of specific synapses

Question 19

What does postsynaptic inhibition cause

Answer 19

General inhibition
All synapses are inhibited equally

Question 20

Why is presynaptic inhibition important

Answer 20

The spinal cord is the neural interface between the brain and the body
It is constantly receiving information via primary afferent fibres
It prevents excessive excitation by filtering out weak or irrelevant signals

Question 21

Monosynaptic stretch reflex Eccles et al., 1961

Answer 21

La afferent from the muscle spindle to the SC could be depressed
No change in motoneuronal membrane potential
No change in motoneuronal excitability or ionic permeability
Inhibition must be presynaptic via stimulation of knee flexors,posterior biceps and semitendinosus

Question 22

What is primary afferent depolarisation PAD

Answer 22

Reduces afferent neurotransmission
Via depolarisation of afferent terminals
Causes reduced NT release likely via GABAergic inhibitory inter neurons

Question 23

Axo axonic synapses

Answer 23

Modulate NT release
Usually GABAergic (inhibitory interneuron on the presynapse) decrease the amount of NT released

Question 24

IPSP

Answer 24

Ionotropic GABAaR open
Causes Cl- ion influx (hyperpolarising stimuli)

Question 25

Chloride equilibrium in PAD

Answer 25

Na+ K+ Cl- cotransporter keeps Cl- potential less negative than the Membrane potential
GABAaR activation causes Cl- efflux and depolarisation

Question 26

What is the Dorsal root potential DRP

Answer 26

Afferent stimulation evoked GABAa receptor activation, Cl- leaves
Primary afferent depolarisation
Dorsal root potential (summed back propagated PAD from many axons)

Question 27

How to record DRP

Answer 27

Proximal electrode of a pair on the root outside of the cord sees a more negative potential
Negativity decays electrotonically
Creates extra cellular negativity (Cl- efflux)
Terminal is depolarised

Question 28

How does PAD inhibit NT release

Answer 28

Inactivates VGCC
Voltage dependent inactivation of NaV
Shunting of conductance (GABAa channel open but net ion flow is 0)

Question 29

What is shunting inhibition

Answer 29

Cl- ion channels are opened
Leakage of signal, membrane is more leaky to current
Reduces net depolarisation by excitatory synapses

Question 30

Name GABAa blockers

Answer 30

Picrotoxin and bicuculline