4 - Synaptic Transmission

Question 1

Define synapse

Answer 1

Region of communication between neurons

Question 2

Define synaptic transmission

Answer 2

Process by which nerve cells communicate

Question 3

Define Neuromuscular junction

Answer 3

Interactions between neurones and muscle

Question 4

Describe neuroeffector junction

Answer 4

Neurones communicating to other tissues

Question 5

Explain the 3 different ways neurones interact

Answer 5

1. Axodendritic synapse: When the axon terminal of 1 neurone forms a functional contact with dendrite of another neurone (most common)
2. Axosomatic synapse: When the axon terminal of 1 neurone forms synapse with cell body (soma) of another neurone
3. Axoaxonic synapse: Axon terminal of 1 neurone forms functional contact with another axon terminal

Question 6

Describe the structure of a synapse

Answer 6

• **Presynaptic neurone: **where signal originates
• Postsynaptic neurone: recieves info from synaptic transmission
• Synaptic cleft: close gap between membranes of 2 neurones (pre/post synaptic membrane respectively)
• The close apposition of the two neurones is not sufficient for information to flow between them. It has been shown that if there is no synapse present an action potential in one neurone only produces a very very small depolarisation (around 1 microvolt) in an adjacent neurone. Clearly this is insufficient to open voltage-gated Na+ channels in the postsynaptic cell and trigger an action potential.

Question 7

Explain the theories of synaptic transmission championed by John Eccles and Henry Dale.

Answer 7

John Eccles
* believed that a low resistance pathway existed between pre and post synaptic neurones.
* And that synaptic transmission is enabled by electrical coupling
Henry Dale
* Believed that AP in presynaptic neurones released a chemical that bridged synaptic cleft and was responsible for AP in postsynaptic neurone.
* Both exist!

Question 8

Describe the structural characteristic of electrical synapses

Answer 8

• Key feature: pre and post synaptic neurones are physically coupled by structures that allow electrical continuity between cells
• Characterised by:
• Very close apposition of pre and postsynaptic membranes (cleft only 3nm)
• Presence of gap-junctions (connect the intracellular space of 2 neurones)
• Gap junction formation: complementary hemi-channels associated with pre and post synaptic membrane that provides a low-resistance pathway between 2 neurones
• Connexons: hemi-channels which are made up of 6 connexin molecules. Extend uniform distance outside the cells
• Allignment of connexons → formation of aq. pores (2nm diameter) between the 2 cells
• These junctions allow action potential in presynaptic neurones to traverse synaptic cleft and depolarise postsynaptic neurone.

Question 9

What are the 2 types of electrical synapses? And where are they located?

Answer 9

Rectifying synapses: only pass info from pre → postsynaptic neurone
* AP in presynaptic neuron causes a subthreshold depolarisation of post. but not vice versa
Bidirectional (or reciprocal) synapses: able to pass info in either direction
* AP causes subthreshhold depolarisation both ways
Location: retina, heart and digestive tract

Question 10

Describe the structural characteristic of a chemical synapse.

Answer 10

• Communication between 2 neurones is enabled by chemical release (neurotransmitter) from presynaptic neurone
• AP → axon terminal of presynaptic neurone, NT is released by exocytosis → diffuses across synaptic cleft (30nm wide)
• Neurotransmitter then binds to complementary receptors on postsynaptic membrane
• NT/receptor binding initiates changes in excitability of postsynaptic neuron
• Neurotransmitters: synthesised by presynaptic neurone and stored in synaptic vesicles
• these vesicles are present in large numbers in axon terminals adjacent to presynaptic membrane

Question 11

Describe the 2 synaptic vessel types in electron microscope

Answer 11

• Electron microscopic analysis of synaptic terminals show 2 major classes of synaptic vesicle within axon terminals
• Most common: small diameter and have a translucent core
• Others are large diameter dense-cored vesicles

Question 12

What are Small Molecule (Classical) Neurotransmitters? And name some of the neurotransmitters.

Answer 12

• First discovered (Otto Loewi and Henry Dale recieving Nobel prize for medicine in 1936)
• Packaged in small diameter, clear vesicles
• 4 major classes of chemical
• Acetylcholine is only NT in its class
• Some NT in other classes perform important cellular functions other than their role as neurotransmitters

Question 13

What are peptide neurotransmitters? And name examples.

Answer 13

Over 50 different substances
Made up of relatively short chains of amino acids
Stored in large-diameter, dark vesicles within axon terminals

Question 14

Describe the physiological processes involved in neurotransmitter exocytosis from the presynaptic neurone (chemical transmission)

Answer 14

• NT release at synapse is initiated by arrival of an AP in axon terminal
• AP spreads through AT → triggers opening of voltage-gated Ca 2+ channels
• Ca 2+ to flow into axon terminal down concentration gradient
• Increase in intracellular Ca2+ concentration triggers migration of synaptic vesicles and their subsequent fusion with the presynaptic membrane.
• Vesicle membrane breaks down. NT is exocytosed → synaptic cleft
• NT diffuses across synaptic cleft and binds to its receptors on postsynaptic membrane
• NT binding to receptors initiates many effects in postsynaptic neuron (determined by type of receptor)

Question 15

Describe the mechanisms by which the duration of action of neurotransmitters is limited.

Answer 15

• Duration of effects of NT is restricted by mechanisms that act to remove it from synaptic cleft. (limits its actions on postsynaptic receptors)
  Diffusion
• Most common
• Diffusion of chemical out of cleft → extracellular space surrounding synapse
• Receptors are restricted to postsynaptic membrane, so NT has no effect anymore
  ** Reuptake**
• Many NT are recycled back into AT, repackaged and used again
• Enabled by specific transporters in AT membrane
  Enzymatic Degradation
• Some NT are broken down by enzymes in synaptic cleft
• E.g: Acetylcholine is broken down by acetylcholinesterase into choline and acetate (inactivated)
• Manipulation of the reuptake and enzymatic degradation of neurotransmitters can affect synaptic transmission.
• Bc. they lower effective conc of NT in SC
• The psychotropic drug cocaine, for example, blocks the reuptake of dopamine, leading to increased dopamine concentration in the synaptic cleft and potentially addictive effects.
• Synaptic Delay: small but significant delay b/n AP arriving in AT and NT effects (around 0.5ms)
• Chemical slower than electrical bc of this
• Sum of: Ca2+ channel opening, Ca2+ diffusion, synaptic vesicle migration, exocytosis, diffusion and binding of NT and changes produced in postsynaptic neurone

Question 16

Describe ionotropic receptors

Answer 16

• Ligand-gated ion channels
• NT binds to ionotopic receptors → channel opens → ions diffuse across membrane according to their conc gradient
• Net effect:
• Depolarisation of postsynaptic neurone (excitatory synapse)
• Hyperpolarisation (inhibitory synapse)
• Excitatory/inhibitory determined by receptor

Question 17

Describe excitatory synapse and an example

Answer 17

• AP in presynaptic neurone produces a transient depolarisation of postsynaptic neurone (after 0.5ms delay)
• A type of depolarising graded potential, but refer to it as excitatory postsynaptic potential (EPSP)
• AP in presyn. → EPSP in postsyn.
• EPSP produced by binding of NT to ionotropic receptors on post-SM → opens ion channel
  E.g: Glutamate and nicotinic acetylcholine receptor
• Appears to be non-selective cation channel that permits the simultaneous movement of both K+ and Na+ across membrane
• Na+ moves into cell, K+ moves out down their respective conc gradients
• Movement of Na+ is helped by EG (attracted to negative resting membrane potential) so more Na+ ions enter than K+ leave
• Net effect: influx of positive charge, responsible for transient depolarisation of EPSP
• EPSP → MP closer to threshold, therefore, increasing excitability of post SN

Question 18

Describe inhibitory synapses and an example

Answer 18

• AP in preSN produces a transient hyperpolarisation of postSN
• Called Inhibitory postsynaptic potential (IPSP)
• AP in preSN → IPSP in postSN
• IPSP produced by binding of NT to ionotropic receptors on postSNM → opens ion channel
• Commonly caused by NT (glycine and gamma-aminobutyric acid), opens ligand-gated Cl- channels
• Conc gradient for Cl- favours the movement on this anion into cell
• Net influx of - charge that results in hyperpolarisation of postsynaptic neurone
• IPSP takes MP away from threshold… Decreases the excitability of postSN or inhibiting it.
  Important Note:
• Bc potential differences that they elicit are produced directly by ion movement, their effects are very rapid onset (synaptic delay 0.5ms) and limited in duration (few 10’s of ms)

Question 19

Describe metabotropic receptors and an example

Answer 19

• Elicits a cascade of molecular events within the postSN that in turn mediate effects of NT
• Common mechanism: G-protein
• Acts as an intermediary between the receptor and an enzyme
• Binding of NT to receptor activates G-protein → stimulates enzyme to produce a small molecule second messenger
• E.g: cAMP, cGMP, Ca 2+, nitric oxide
• Second messengers can freely diffuse through cytoplasm of postsynaptic neurone → produce indirect effects
• Such as: enzyme activation, regulation of gene transcription, ion channel opening and modification of the sensitivity of ionotropic receptors
• E.g: Muscarinic acetylcholine receptor
• Found on cardiac muscle cells
• Acetylcholine binds to this receptors → activates G protein complex → second messenger formed → acts intracellularly to open K+ channel.
• K+ leave cell along conc gradient → membrane hyperpolarises → cardiac muscle inhibited
• Fairly slow in onser (100ms)
• Not involved in neuronal circuits that require rapid communication
• NT can result in changes to metabolism of neurones → effects are generally more persistent than ionotopic

Question 20

Describe the different types of summation and be able to explain how these mechanisms underpin the large number of decisions we make every day.

Answer 20

• In NS, neurones gave many synaptic inputs
• They add up all EPSPs and IPSPs → if MP reaches threshold → AP generated
• Summation: adding of EPSPs and IPSPs
• The Initial segment since this is where AP originate
• Bc GP only affect regions close to where they originate, synapses that are close to initial segment have a larger impact on neurone than further synapses
• So, excitatory/inhibitory effects on the soma or proximal dendrites affect neurone to greater extent than distal dendrites
• The outcome of this summation determines what you choose for breakfast, when you will cross the road and the hundred of thousands of other decisions that you make every day.

Question 21

Describe spatial summation

Answer 21

• N1 and N2 form excitatory synapse w/ N3
• Stimulate N1 or N2 alone → EPSP in neurone 3 (doesnt reach threshold, no AP)
• Stimulate N1 and 2 together, 2 EPSPs add together, N3 membrane reaches threshold. AP produced.
• called Spatial summation (from spatially distinct inputs)

Question 22

Describe Temporal summation

Answer 22

• 2 neurones linked by excitatory chemical synapse
• Stimulate N1 once → EPSP in N2 (below threshold)
• 2 stimuli to N1 in short succession, EPSP caused by second AP arrives before first one has decayed
• 2 EPSPs add together → N2 reaches threshold (AP occurs)
• Temporal Summation