L2 neurons and neuronal networks :

transmission and inhibition

Synaptic communication

Left image: Presence of NT vesicles in presynaptic terminal. NT bind to receptors that are
held on PSD (postsynaptic density). PSD can change receptor expression by
increasing/decreasing number of receptors.

Depending on the NT, either an IPSP or EPSP is produced by opening anion channels or
opening cation channels respectively.

Eg. If GABA (inhibitory NT) is diffused across the cleft, it opens the GABA A channel
which fluxes Cl- ions into the postsynaptic cell which produces a IPSP so less likely to fire a
potential

Mechanism of NT release

1. The action potential arrives at the presynaptic terminal

2. Change in voltage across membrane triggers voltage gated Ca2+ channels to open
3. Calcium influx
4. Triggers NT vesicles to dock onto SNAP snare complex
5. Which opens membrane and allows NT to be released
6. NT diffuses across cleft and binds to receptors on postsynaptic

Inhibition of NT action

 Reuptake into presynaptic terminal

o Energy efficient. NT can be repackaged and reused
 Reuptake into astrocytes
o Can store and release NT, therefore can control how synapse functions
 Enzymatic degradation
o Not v energy efficient cause have to remake NT
 Diffusion
o Some NT will just diffuse into blood and get degraded

Reversal potentials

AKA equilbrium potential meaning the point at which net flow of ions (or a specific ion) is
zero, but if you change the membrane potential you change the response to that ion. eg.
excitatory response could be an inhibitory response.

The top diagram shows normal expression at -75mV. The gate (red line) opens and sodium
influxes into the cell resulting in v large depolarising current. No potassium current as current
has been driven by sodium (shown by green x )
The bottom diagram shows a membrane at -40mV. If a gate is opened there is much smaller
electrostatic force to drive sodium into the cell because charge differential is weaker so less
sodium flows into cell → therefore smaller potential produced.

Membrane at -25mV produces an even smaller sodium potential, which results in potassium
leaving the cell.

Membrane at -10mV we reach reversal potential, where flux of potassium and sodium will be
equal.

Membrane at 0mV you flip response of cell, resulting in large potassium eflux.

Red line represents end plate potential at NMJ. When the end plate potential reaches 0mV the
flow of sodium and potassium cancel out, which causes decay of graded potential. Unless
input has been strong enough to pass the threshold, which would result in action potential
being generated → so motor response

This means an action potential can never be generated itself unless threshold is passed.

IPSPs

In IPSPs if you clamp the neuron at a lower potential than Vm, No Cl- will enter the neuron.

If clamped at even lower like -100mV it can result in Cl- leaving the cell and result in an
excitatory response.

EPSPs and IPSPs

 Both are sub threshold events which determine whether neuron/muscle will reach
threshold to fire an action potential
 EPSPs generatre depolarisation → more likely to fire
 IPSPs generate hyperpolarisation → less likely to fire
 The potential to fire an action potential is based on balance of EPSPs and IPSPs
which act to cancel each other

The knee jerk reflex is an example of when EPSP and IPSP act together to produce a smooth
movement.
One action potential, one triggers and IPSP which makes it less likely to contract the
hamstring muscle, and one triggers an EPSP which makes it more likely to contract the quad
muscle

Inhibition

There are multiple types of inhibitory responses including feedforward, feedback, lateral and
recurrent.

If we have inhibitory interneurons in the circuit (right diagram), the neuron in the middle
which was driven more strongly by stimulus, will have the greatest effect on the inhibitory
neurons. It will be the strongest activator of the inhibitory interneurons, and give them greater
drive to inhibit presynaptic inputs and some postsynaptic inputs. This will result in only the
central component being passed on.

Motor neuron produces an action potential, which through the Renshaw cell inhibits itself.
This also allows brain to integrate in the system, through descending influences. Action
potentials from the brain can also excitate or inhibit the Renshaw cell, which can overrule the
inital potential. eg. when testing hot water and you decide to keep your hand there until it gets
too hot and hand has to move away

Synaptic modulation

1. An excitatory neuron fires

2. AP is generated
3. Signal is passed to all targets
4. Postsynaptic response is elicited

Presynaptic inhibition

1. An excitatory neuron fires

2. AP is generated
3. An inhibitory neuron fires blocking NT release at 1 synapse
4. So postsynaptic response only produced in 2 of 3 targets

This mechanism allows for fine tuning. More specific conrol due to precise inhibtion of
specific synapses

Postsynaptic inhibition

1. Excitatory and inhibitory neuron fire

2. EPSP and ISPS result in a below threshold graded potential
3. No AP is generated
This blocks gross signalling. ALl synapses inhibited equally.