Synapses

Question 1

What is a synapse?

Answer 1

Contact structure between a neurone and a post-synaptic cell.

Where APs of presynaptic neurone trigger an electrical response in the postsynaptic neurone/cell.

Question 2

What are electrical synapse?

Answer 2

Electrical synapses are GAP JUNCTIONS, the zone of least electrical resistance between the two cells.

Question 3

Where are electrical synapses found?

Answer 3

Rare in higher vertebrates, but still functionally important.

Found many in invertebrtaes and in vertebrates like fish.

Question 4

What is the structure of Electrical synapse?

Answer 4

Gap junctions form pores through which ions can pass through PM to cytoplasm.

6 Connexins assemble to form a Connexon, on each side of PM.

Forming a central channel between PMs.

Each connexin has 4 TM segments, and central channnel is very narrow at 3.5nm.

Question 5

What are properties of electrical synapses?

Answer 5

3.5nm synaptic cleft = very narrow central channel = narrow synaptic cleft.

Very short synaptic delay.

Low sensitivity to pharmacological agents.

Bidirectional is possible.

Offers cytoplasmic continuity between pre and post synaptic cells.
- Electronic propagation

Question 6

What are the physiological roles of electrical synapses?

Answer 6

RAPID neurotransmission.

Able to synchronise the electrical activity of a population of neurones.

Can have metabolic itneractions between pre and post syanpse.

Form functional cell groups during development.

Question 7

How can electrical synapses be unidirectionaL?

Answer 7

Crayfish - synapse between motor neurone and giant axon in abdominal ganglion.

The electrical synapse is said to be rectifying, because stimulating the motor neurone does not cause AP in Giant axon, but stimulating giant axon triggers AP in motor neurone!

Question 8

Names of different types of chemical synapses?

Answer 8

Axosomatic
Axodendritic
Axoaxonic.

Question 9

What are the events taking place in an chemical synapse?

Answer 9

Membrane depolarisation of axon terminal by AP.

VG Ca2+ channels open, and influx of CA2+.

Ca2+ triggers release of NT by exocytosis.

NT binds, triggers open/clsoing of ion channels and modification to EM = PSP.

Question 10

What is the fate of Ca2+ after AP of synaptic terminal?

Answer 10

AFter Ca2+ spike,

Ca2+ pump using ATP.

Ca2+ binds to calmodulin.

SERCA reuptake into reticulum.

Na+/CA2+ exchanger.

Question 11

What is a post-synaptic potential?

Answer 11

PSPs are variations in Em of postsynaptic cell triggered by binding of NT to receptors.

IPSP = hyperpolarisation
EPSP = depolarisation.

Question 12

Ionic selectivity of NT receptors?

Answer 12

nicotinic AChR = Na+ and K+ = cationic.

GABAa receptor is cationic = chloride.

Question 13

Why called EPSP or IPSP?

Ionotropic vs Metabotropic speed and duration of PSP?

Answer 13

If sufficiently ample, EPSP will trigger an APm whereas the IPSP reduces chance to reach AP threshold

Ionotropic will be rapid, but transient whilst metabotropic will be slower and more durable response.

Question 14

What are the properties of chemical synapses?

Answer 14

Asymmetric

WIDE synaptic celft - 30-50nm

NT released in cleft, binds to receptors on PS cell = unidirectional

Synaptic delay 0.3ms-few ms

EPSP or IPSP

VERY sensitive to pharmacological agents, and transient due NT reuptake/degradation.

Question 15

What are transporters of synaptic vesicle membrane?

Answer 15

ATPase proton pump:

Active transport to uptake H+ in vesicle.

Vesicular NT transporter allows H+ to export vesicle, down gradient, and take up NT in exchange.

Question 16

What are the roles of some vesicular proteins?

Answer 16

Synapsin 1 binds to actin cytoskeleton to hold vesicles in Reserve Pool.
= Synapsins link synaptic vessicles to cytoskeleton.

CAM-KII (In vesicular membrane) phosphorylates Synapsin 1 to release Reserve pool vesicle…. (Calmodulin-dependent kinase).

Synaptotagmin and Synaptobrevin involved in binding to PM proteins (Syntaxin and SNAP-25)
= SYNAPTOBREVIN AND SYNAPTOTAGMIN attach with SNAP-25 and Syntaxin to dock synaptic vesicle to PM>

Question 17

What proteins are involved in NT vesicle docking?

Exocytosis?

Answer 17

Synaptotagmin and Synaptobrevin are vSNAREs (Vesicular Membrane)

vSNAREs form a four helical bundle with tSNAREs (Syntaxin and SNAP25), for vesicular docking. and SNARE complex exerts force to pull membranes together into hemi-fused state
= Primed.

Arrested in hemi-fused state by Complexins.

Synaptotagmin is Ca2+ sensitive, when Ca2+ binds, Complexins are displaced and full fusion event.

Question 18

What are Clostridial toxins?

Answer 18

Tetanus toxin = causes permanent contraction (tetany)

Botulinum toxin = blocks contraction of muscle.

Question 19

What is target of Botulinum toxin?

Tetanus toxin?

Answer 19

Target different proteins of SNARE complex in cholinergic neurones, leading to flaccid paralysis.

= ACh not released at NMJ!

Tetanus targets Synpaptobrevin in spinal cord inhibitory interneurones.
= Prevents release of GABA, causing disinhibition of motor neurones and permanent contraction

Question 20

What are the inactivation pathways of different NTs?

Answer 20

NA : Presynaptic reuptake
= using Na+/NA symporter in pre-synaptic neurone.

ACh = AChE degradation in synaptic space.
Reuptake of choline w/ Na+ in choline/Na+ symporter.

Question 21

What are the criteria of a NT?

Answer 21

Synthesis system and precursors at the presynaptic level.
= PRESYNAPTIC AXON TERMINAL!

Neuropeptides are synthesised in the soma and transported along MT tracks to terminal.

Depolarisation of presynaptic membrane triggers release in a Ca2+ dependent mechanism.

Rapid inactivation mechanism = transient effect.

Leads to changes in conductance/polarisation of post-synaptic membrane.

Endogenous/exogenous molecule produces Post syanptic action.

Question 22

How can synapses integrate?

Answer 22

Neurones algebraically add PSPSs received from other neurones.

Temporal summation = very close PSPs in time generated by SAME synapse

Spatial summation
= Addition of PSPs from different synapses recieved simultaneously.

Question 23

What are properties of PSPs?

Answer 23

IPSP/EPSP depending on NT receptor/channel.

Can be summed:
Temporally = PSPs close in time at SAME synapse.
Spatially = different synapses sum simultaneously.

LOCAL event - decremental propagation, the PSP decrease with distance form synapse.
= Em variation decreases.
= LOW space constant.

High space constant means PSP will have less decremental propagation