Synapses

Question 1

Synapses

Answer 1

• It is a functional junction between 2/more neurons. Effectors? (occurs at effectors)
• Consist of presynaptic neuron/s and postsynaptic neuron/s.
• Boutons/end feet of presynaptic neurons can synapse on the dendrite (major kind of synapse), soma, or axons of postsynaptic neurons.
• Interneural communication can be chemical or electrical.

-Chemical synapses display plasticity
and delay of ~0.5ms

Question 2

Characteristics of electrical synapses

Answer 2

There is cytoplasmic continuity between the involved cells in this junction, info transferred rapidly, movement bi-directional. Cells function as Syncitium.

-There are gap junctions which are areas of low resistance. They allow the ionic flow of local current between adjacent cells via Connexons (protein tubes*) in the cell membrane. (Ø 16-20 Å)
Note hemichannels.

• Metabolic signals involved eg cAMP and IP3
• Makes functioning as a syncytium possible.
• Electric synapses are Found in cardiac & many types of smooth muscle.
• Found in neural circuits such as arousal from sleep, emotions & memory.

-Currently accepted as a complimentary
form of communication.

Question 3

Types of Circuits in Neuronal Pools

Answer 3

-Neuronal pools are functional groups of neurons that integrate incoming information with an output. viz a processing unit. NB there are constellations of these units!

-The configuration of a neuronal circuit is dependent on its function.
Neuronal pools are dynamic.

• Three examples of how circuits can be configured:
  1. Convergent
  2. Diverging
  3. Reverberating

Question 4

1. Convergent circuit

Answer 4

– stimulation of a single postsynaptic neuron from multiple inputs, resulting in either strong stimulation or inhibition

Question 5

2. Divergent circuit

Answer 5

– one incoming fiber stimulates an ever-increasing number of fibers, often amplifying circuits. High divergence ratios are not possible with electrical synapses

Question 6

3. Reverberating circuit

Answer 6

– chain of neurons containing collateral synapses with previous neurons in the chain.
Remember the synaptic delay is ~0.5ms
Multiple outputs?

Question 7

Organization of a synapse

Answer 7

• Ultrastructural & proteomic studies of end-feet/boutons show special arrangements: large numbers of mitochondria; vesicles with neurotransmitters (NT)* & neuropeptides, active zones, Ca+2 voltage-gated channels, specialized pumps eg. Choline transporter (CHT)
• Most NTs synthesized in cell body transported via axoplasmic transport to end-feet.
• Release of NT is quantal in nature where each quanta generates a miniature endplate potential (MEPP)
• Auto receptors on the surface of the presynaptic neuron provide negative feedback of the transduction process.

Question 8

Neurotransmitters (NT)

Answer 8

Are endogenous species secreted by the presynaptic neuron that alters the potential of the postsynaptic cell.

A growing family of compounds (50 - 100)

Question 9

Neurotransmitters groups

Answer 9

Neurotransmitters can be broadly split into two groups:

1) ‘Classical’ small molecule NTs including monoamines (ACh, serotonin, histamine) and the amino acids (glutamate, GABA, glycine)

Within the category NTs, the biogenic amines (dopamine, noradrenaline,
serotonin and histamine) are often referred to as a ‘discrete group’ because of their similarity in terms of their chemical properties

2) Large molecule NT (includes neuropeptide) such as substance P (acts as as a neurotransmitter and as a neuromodulator.), encephalin, vasopressin

Question 10

Major neurotransmitters in the body and brief role in the body

Answer 10

1. Acetylcholine = spinal cord, control muscles and neurons in the brain to regulate memory, most instances it is excitatory
2. Dopamine = Feelings of pleasure when released by the brain reward system. Dopamine many functions, depending on where in the brain it acts, usually inhibitory.
3. GABA = major inhibitory neurotransmitter in the brain.
4. Glutamate = most common excitatory neurotransmitter in the brain
5. Glycine = Used mainly by neurons in the spinal cord, always acts as an inhibitory neurotransmitter.
6. Norepinephrine = Acts as a Neurotransmitter and a hormone. in the PNS it is part of fight of flight. In the brain, it acts as a NT regulating normal brain processes. Usually excitatory but is inhibitory in few brain areas

7.

Question 11

Receptors (types)

Answer 11

Located on pre + postsynaptic neurons.
The receptor density, which is dynamic affects the sensitivity of response

There are 2 broad types/categories:

1. Ionotropic receptors (Channel linked) and
2. Metabotropic receptors (G-protein linked)

Question 12

A) Ionotropic receptors (channel linked)

Answer 12

• 5 Large protein complexes form ionic pores in membrane (amino acid sequence ‘controls’ the type of ion that moves through the pore )

-NT binding to a receptor induces a conformational change. which changes pore diameter which allows transmembrane movement of ions.
eg ACh, glycine & GABA

• Gating of the channel is direct
• Ionic flow occurs down concentration gradient. Recall the rate?

-This alters electrical status of postsynaptic neuron.

Question 13

B) Metabotropic receptors (G protein-linked)

Answer 13

-Smaller domain ~ single polypeptide comprising 7α helices)

• NT binding to the receptor activates G-proteins֘• which in turn activates an enzyme system* which produces a 2nd messenger
  (eg cAMP, cGMP, DAG, IP3).

The 2nd messenger:
1. Affect biochemical changes by increasing metabolites and/or ionic pore diameter →∆ ionic flux

2. Gating of the channel is indirect
3. Response is slower but of longer duration
4. Amplification of response is possible (very important)

NB Many NTs bind to both receptors types resulting in a rapid & sustained response.

Question 14

Events at a chemical synapse

Answer 14

1. Arrival of nerve impulse opens voltage-gated calcium channels.
2. Ca+2 influx into the presynaptic terminal.
3. Ca+2 → intracellular messenger stimulating synaptic vesicles to fuse with membrane & release NT via exocytosis.
4. Ca+2 removed from the terminal by mitochondria or calcium pumps.
5. NT → synaptic cleft and binds to a receptor on the postsynaptic membrane
6. Receptor changes the shape of ion channel opening it and changing membrane potential
7. NT is quickly degraded by enzymes or taken back up by astrocytes or presynaptic membrane transporters.

Note: For each nerve impulse reaching the presynaptic terminal, about 300 vesicles are emptied into the cleft.

Question 15

Postsynaptic potentials

Answer 15

-NT + receptors mediate changes in membrane potential of postsynaptic neurons depending on:

> The concentration of NT that is released + receptor type
The duration of NT-R complex association.

The two types of postsynaptic potentials that can develop are:
EPSP – excitatory postsynaptic potentials
IPSP – inhibitory postsynaptic potentials

Question 16

1. Excitatory Postsynaptic Potential (EPSP)

Answer 16

• The diagram shows epsp, the cells m pot changes from resting to the firing point

Question 17

Summation

Answer 17

• A single EPSP cannot induce an action potential in the PSN
• EPSPs must summate temporally or spatially to induce an action potential
• In temporal summation, the presynaptic neuron transmits impulses in rapid-fire order (high frequency)
• Spatial summation – many presynaptic neurons stimulate a single postsynaptic neuron

Question 18

2. Inhibitory Synapses and Inhibitory Postsynaptic potentials (IPSPs)

Answer 18

• Neurotransmitter binding to a receptor at inhibitory synapses:
  1. NT-R complex increases membrane permeability to K+ and/ or Cl- ions.
  2. Inner surface hyperpolarises.
  3. Reduces the postsynaptic neuron’s ability to produce an Action potential.

[stimulus gets the cell more negative, so the cell will have a harder time getting to positive and hence decrease the chances of getting threshold, making it unlikely to get an action potential]

Question 19

Can presynaptic events be controlled?

Answer 19

• Synaptic activity is often modulated presynaptically as well
• Remember presynaptic activity is a multi-stepped process
• The modulation involves the need for a “special” presynaptic circuit
• Both facilitation or inhibition is possible

Question 20

Presynaptic inhibition

Answer 20

-GABA released at axo-axonal synapse inhibits opening calcium channels in synaptic knob/
-This action decreases the amount of NT
released when AP arrives.

-The net result is postsynaptic neuron
stimulated less intensively.

[Action potential gets to presynaptic button causes less calcium to enter the terminal and then that will lead to less neurotransmitter being released to the synaptic cleft = reduced effect on postsynaptic membrane]

Question 21

Presynaptic facilitation

Answer 21

Activity at the axo-axonal synapse increases the amount of NT released when AP arrives at the axonal knob.

This effectively enhances and prolongs the effect of the NT i.e. sustained stimulation.

Serotonin is inhibitory in pain pathways

[Serotonin released leads to activation of calcium channels, more calcium enters axonal knob, more neurotransmitter released, increased effect on postsynaptic membrane]

Question 22

Synaptic plasticity

Answer 22

• Effectiveness of chemical synapses fluctuates thus affecting the transfer of information.
• Repetitive high frequency of stimulation (tetanus) by presynaptic neuron results in synaptic facilitation (~1sec) followed by augmentation (slower phase of increase in efficiency) in PSN.
• Can these observations be due the presence of increased residual Ca+2 in the active zones?
• An explanation for learning and memory as well as ability to distinguish between a proper signal & noise!

Considerable work being done on the hippocampus.

Synapses can change depending on how they are stimulated.

Question 23

Characteristics of chemical synapses

Answer 23

• Cleft so no physical continuity between neurons.
• Transmission - chemically mediated (NT release, diffusion, receptors)
• Transfer of information is unidirectional
• Pre- and postsynaptic ion currents

-Delay (1-5ms) hence slower than electrical synapse.

The postsynaptic effect could be excitatory (EPSP) or inhibitory (IPSP).

• Makes synaptic gain possible
• Allows for plasticity

Question 24

The following criteria used to identify a Neuro Transmitter:

Answer 24

1) Present in appreciable concentration and the presence of enzymes for its synthesis
2) Chemically identified
3) Application on postsynaptic cell must mimic presynaptic stimulation.
4) Response must be blocked in a dose-dependent manner by an antagonist (Δ agonists)
5) Evidence of an enzyme system for degradation.

Question 25

Enzyme systems –> 2nd messenger

Answer 25

Adenylyl cyclase = cAMP
Phospholipase C = DAG + IP3
Guanylyl cyclase = cGMP

Question 26

From pre-synaptic to Post-synaptic

Answer 26

1. Action potential reaches the terminal
2. Voltage-gated calcium channels open
3. Calcium enters the axon terminal
4. Neurotransmitter release and diffusion
5. Neurotransmitter binds to postsynaptic receptors
6. Neurotransmitter removed from the synaptic cleft.

When the neurotransmitters are ready to be released from the vesicles, the vesicles are docked and held in place by fibers called Synaptobrevin, syntaxin and SNAP 25, SNAREs, then when secured in place they release the Neurotransmitters. (calcium is the cue for this release)