Synaptic Transmission and Plasticity

Question 1

What is the neuron doctrine?

Answer 1

Santiago Cajal - neurons communicate by contact not continuity. The transfer of information from one neuron to another is at a special site called a synapse, by synaptic transmission.

Question 2

What are the two means of synaptic communication?

Answer 2

1) Electrical communication via gap junctions
2) Chemical communication through chemical synapses

Question 3

What is the function of electrical synapses?

Answer 3

Electrical synapses allow the direct transfer of current from one neuron to the next - relatively uncommon in mammalian neural systems. They are very fast.

Question 4

Where are electrical synapses found?

Answer 4

a. Electrical synapses occur at specialised sites called gap junctions.
b. Electrical synapses are often found in areas of highly synchronised neuronal activity - they help neurons to synchronize their activity.
c. They are particularly common during embyronic development and post-natal brain development.

Question 4

How do electrical synapses occur?

Answer 4

a. The channel allows flow of ions from the cytoplasm of one cell –> cytoplasm of another cell. Most gap junctions allow the transfer of ions equally well in both directions (unlike most chemical synapses) - bidirectional.

b. When two neurons are electrically coupled, then an action potential in the presynaptic neuron can cause a small amount of electric current to flow into the other cell - this current causes a post-synaptic potential (PSP) - usually a very small current (not long enough to trigger an AP in the postsynaptic cell)

c. Several PSPs occuring simultaneously (from various presynaptic neurons) can add together to cause an action potential - this is an example of synaptic integration

Question 4

What is the structure of electrical synapses?

Answer 4

6 connexin subunits form a channel (connexon) and two connexons (one from each cell of the synapse) form a gap junction channel (direct cell to cell connections) - cells are 3nm apart

Question 5

Where do chemical synapses occur?

Answer 5

Site of communication: The pre and post-synaptic cells are separated by a synaptic cleft.

Question 6

What is the presynaptic element of chemical synapses?

Answer 6

a. The presynaptic element is usually an axon terminal - contains:
i. Synaptic vesicles: many small membrane encloses vesicles containing neurotransmitters - 50nm wide
ii. Secretory granules: larger membrane enclosed granules containing larger neurotransmitters - 100nm wide

Question 6

What is membrane differentiation?

Answer 6

b. Membrane differentiation: the dense accumulations of proteins within or adjacent to the membrane on either side of the synaptic cleft collectively
i. Active zone: the actual zone of neurotransmitter release
ii. Post-synaptic density: the proteins that are thickly accumulated in/under the post-synaptic membrane. Contains
1. Neurotransmitter receptors
2. Receptors that convert intracellular chemical signals into a change of Vm in the post-synaptic cell

Question 7

What are the 3 types of CNS synapses?

Answer 7

i. Axodendritic –> axon to dendrite
1. Typically onto spines
2. Excitatory

ii. Axosomatic –> axon to cell body
1. Excitatory or inhibitory

iii. Axoaxonic –> axon to axon
1. Presynaptic
2. Usually inhibitory

Question 8

What is the cascade of events of chemical synapse transmission?

Answer 8

a. Action potential reaches nerve terminal
b. Depolarisation of presynaptic terminal opens ion channels allowing calcium into cell
c. Ca2+ triggers release of neurotransmitter from vesicles
d. Neurotransmitter binds to receptor sites on postsynaptic membrane
e. Opening and closing of ion channels cause change in postsynaptic membrane potential
f. Action potential propagates through next cell
g. Neurotransmitter is inactivated (degradation) or transported back into presynaptic terminal (reuptake)

Question 9

What are the two types of chemical receptors?

Answer 9

Ionotropic and metabotropic receptors

Question 10

What are ionotropic receptors?

Answer 10

Ligand gated ion channels that are closed in the absence of neurotransmitter and open when a neurotransmitter molecule binds to an extracellular domain.

a. Receptor and effector are the same protein - ligand gated ion channels
b. Fast and simple
c. Ex. glutamate receptors at CNS synapse
i. 4 peptide subunits as tetrameric membrane protein
ii. Different subunits (ex. 4 & 6 AMPA & NMDA subunits) with subtly different permeation and kinetic properties
iii. Ligand-binding, gating and channel pore regions

Question 11

Describe metabotropic receptors.

Answer 11

Metabotropic receptors are G-protein coupled receptors - binding of a neurotransmitter to the receptor activates a G-protein which then activates effector proteins (e.g ion channels or enzymes) –> leading to cellular effects

Question 11

What are key features of metabotropic receptors?

Answer 11

a. The same neurotransmitter can have different post-synaptic actions depending on which receptor it acts upon.
b. Receptor and effector are different proteins.
c. 2nd messenger system involved.
d. Slow complex and lots of modulation.
e. Ex. dopamine receptors

Question 12

What is the transmembrane flux?

Answer 12

The transmembrane ion flux (due to ionotropic or metabotropic receptor stimulation) determines the membrane potential response.

Question 13

What is the difference between the Excitatory Post-Synaptic Potential (EPSP) and the Inhibitory Post-Synaptic Potential (IPSP)?

Answer 13

Excitatory post-synaptic potential (EPSP):
* Transient postsynaptic membrane depolarisation (Na+ influx, cation influx), caused by the binding of excitatory neurotransmitters, that make the post-synaptic cell membrane more likely to generate an action potential

Inhibitory post-synaptic potential (IPSP):
* Transient postsynaptic membrane hyperpolarisation (Cl- influx, anion influx), caused by the binding of inhibitory neurotransmitters, that make the postsynaptic membrane less likely to generate an action potential

Question 14

What is the correlation between NMDA receptor and glutamate?

Answer 14

Glutamate activates AMPA and NMDA receptors.
In a healthy synapse, a regulated amount of glutamate is released from the presynaptic neuron.
Activation of AMPA receptor causes influx of sodium into postsynaptic neuron –> depolarisation of postsynaptic neuron.
With enough depolarisation, Mg+ block in NMDA receptor is relieved –> sodium + calcium influx into postsynaptic neuron
Calcium influx is involved in many signalling cascade

Question 15

What is a consequence of a disruption of ion homeostasis?

Answer 15

Ischaemic stroke

1. During stroke the blood supply + substrates (oxygen and glucose) supply is impaired
2. Energy depletion –> neurons cannot generate enough ATP to keep their ion pumps working properly
3. The resting membrane potential gets depolarised (ex. reduced activity of Na+/K+/ATPase, increased extracellular K+, decreased intracellular K+)
4. Voltage gated Ca2+ channels in presynaptic neuron opens –> unwanted influx of calcium ions into presynaptic neuron
5. Increase in intracellular Ca2+ triggers synaptic release of excess glutamate
6. Excess glutamate overstimulates postsynaptic glutamate receptors (especially NMDA) –> abnormally high levels of Ca2+ influx into postsynaptic neuron
7. Cytotoxic enzymes including proteases, nucleases and caspases activated –> neuronal death
8. Neurons that die release its own supply of glutamate –> overstimulating and killing other neurons
9. Stroke initiates a vicious cyle of excess glutamate release –> excitotoxicity –> neuronal death

Question 16

What is synaptic integration?

Answer 16

A process by which multiple synaptic potentials combine within a post-synaptic neuron.

• Most CNS neurons receive thousands of synaptic inputs.
• ESPSs and ISPSs are integrated spatially and temporally into an action potential by neural computation.

Question 17

What is EPSP summation and what are the two types?

Answer 17

EPSP summation allows for neurons to perform sophisticated computations.

• EPSPs are added together to produce significant post-synaptic depolarisation:
• Spatial summation - EPSPs generated at different sites are added together
• Temporal summation - EPSPs generated at the same synapse in rapid succession

Question 18

What are the two types of inhibition?

Answer 18

a. Hyperpolarising inhibition
i. Action: inhibitory synapse causes hyperpolarisation to reduce the likelihood of an action potential
ii. IPSP can reduce the size of an EPSP to take membrane potential away from action potential threshold

b. Shunting inhibition
i. Action: inhibitory synapse inhibits current flow from soma to axon hillock

Question 19

Which factors affect nerve excitability?

Answer 19

• Type of synaptic inputs (EPSPs and ISPSs)
• Number and activity of synapses
• Intrinsic excitability (how easily a neuron can generate an action potential in response to a particular stimulus) - determined by number + type of channels, shape of neurons

Question 20

Which cellular factors may cause seizures?

Answer 20

a. Too little inhibition
b. Too much excitation
c. Altered synapse number or efficacy
d. Increased intrinsic excitability
e. Changes in action potential

Question 21

What is habituation?

Answer 21

The decrease of an innate response to a frequently repeated stimulus.

Process:
i. Presynaptic reduction in glutamate release at sensory neuron to motor neuron synapse
1. Decreased Ca2+ influx during action potential into presynaptic neuron
2. Reduced transmitter release at terminals

Question 22

What is sensitation?

Answer 22

The increase of an innate response to a frequently repeated stimulus.

Process:
i. Presynaptic increase in glutamate release at sensory neuron to motor neuron synapse.
1. Increase in Ca2+ influx during action potential into presynaptic neuron (due to change in the property of a different set of ionic channels in the presynaptic membrane)
2. Increased transmitter release at terminals