Neuroscience Week 3

1. NT synthesised and stored in vesicles/granules at the terminal
2. AP reaches the terminal and causes membrane depolarisation
3. voltage gated Ca²⁺ channels open
4. Ca²⁺ rushes in
5. Ca²⁺ stimulates vesicles to fuse to the presynaptic membrane
6. release of NT into the synaptic cleft via exocytoses
7. NT in the cleft binds to receptors on postsynaptic membrane
8. ion channels open or close on postsynaptic membrane
9. resulting ion current creates postsynaptic potential (PSP). EPSP or IPSP travels as a graded potential
10. vesicles are recycled and refilled with NT
11. NT is removed from the cleft via various mechanisms
12. Ca²⁺ is removed from the presynaptic terminal into the ECF by transporters

SNAREs are a family of proteins that enable the binding and fusion of adjacent membranes of the docked vesicle and cell to allow NT release.

Stimulates:
*the vesicles to fuse to the presynaptic membrane so NT may be released
*more vesicles to move to the active zone
*SNARE proteins to exocytose vesicles

elimination of Ca²⁺ would see no NT release

1. binds to post-synaptic membrane receptors to exert its effects
2. diffuses away from the cleft
3. is degraded by postsynaptic enzymes (which prevents re-binding of the same NT molecule)
4. binds to presynaptic receptors for reuptake (conservation)
5. binds to receptors on astrocytes, which are taken up and redistributed or metabolised

EPSP: excitatory post synaptic potential. occurs when membrane is depolarised, and increases the change of a postsynaptic cell firing an AP. e.g. it opens Na⁺ or Ca²⁺.

IPSP: inhibitory post synaptic potential. occurs when the membrane is hyperpolarised, and decreases the chance of a postsynaptic cell firing an AP. e.g. it opens Cl^- or K⁺ channels.

It begins as a graded potential. when depolarisation reaches critical point (-40mV at hillock), massive depolarisation occurs rapidly (within a millisecond).

a)
1. a point stimulus increases Na⁺ permeability, and causes depolarisation
2. if threshold is reached, voltage gated Na⁺ channels open
3. Na⁺ flows into the cell at that point
4. this causes massive depolarisation causing overshoot
5. the flow of ions moves along the membrane, slightly depolarising the next point, causing more voltage gated Na⁺ channels to open at nodes of Ranvier
6. AP propagates along axon

b)
7. voltage gated Na⁺ channels close
8. voltage gated K⁺ channels open and K⁺ flows out of the cell to return it to the original electrical gradient
9. NaK ATPase pump returns the cell to original chemical gradient (2 K⁺ in, 3 Na⁺ out)

A) -65mV

b) +40mV

c) -40mV

Secretory granules: larger (100nm), slower release, not exocytosed at active zones, requires higher/more diffuse Ca²⁺ levels than vesicles, transports active peptide NT and transports it from the Golgi to the terminal.

synaptic vesicles: smaller (50nm), faster release, exocytose at active zone, are stimulated by local increases in Ca²⁺ concentration, stores amine and aa NTs which are packaged by transporter proteins.

The rising phase (depolarisation) on an AP graph would be unattainable since the intracellular environment would be unable to become more positive with no sodium rushing in

*alters signal conduction in neurons by blocking the fast voltage gated sodium channels
*with sufficient blockage the membrane of the postsynaptic neuron will not depolarise and will fail to transmit an action potential.
*this creates an anaesthetic effect by not merely preventing pain signals from propagating to the brain by by stopping them before they begin.

A. synaptic transmission via ligand-gated ion channels (ionotropic receptors). NT binds to a receptor that forms part of an ion channel. NT binding opens the pore.
if it is permeable to Na/Ca --> depolarisation --> EPSP. e.g. ACh nicotinic receptor
if it is permeable to Cl/K --> hyperpolarisation --> IPSP. e.g. GABA receptor

b. transmission via g-protein coupled (metabotropic) receptors. EC domain binds NT, IC domain binds g-protein. NT binds and activates the g-protein, which then (1) opens/closes ion channels (short cut) (2) initiates 2nd messenger cascade.
the effects, in sec/mins, include opening or closing channels, changing enzyme activities, changing gene expresion.

c. a postsynaptic potential can only be generated if the immediate postsynaptic membrane has voltage gated Na⁺ channels. this is referred to as an EPSP.

Signal amplification. direct transmission occurs when 1 NT molecule activates only 1 ion channel. however with indirect transmission, 1 NT molecule can potentially affect many ion channels:
*NT binds to metabotropic receptor
*1 receptor has many g-proteins
*each g protein has many primary effectors
*each primary effector has many second messengers
*each second messenger has many cytoplasmic rxns
*therefore potentially many ion channels are affected

1. the number of coactive excitatory synapses and/or the AP frequency of the presynaptic neuron (i.e. spatial or temporal summation)

2. the distance the synapse is from the hillock (closer the better coz graded potentials weaken over distance)

3. the properties of the membrane (must have sodium channels)

A) since the E_Cl- = -65mV, (which is the same as resting membrane potential), if the postsynaptic memrane was already depolarised (i.e. more positive than -65mV), the opening of Cl- channels would act to hyperpolarise the cell.

b) since the E_Cl- = -65mV, (which is the same as resting membrane potential), the opening of Cl- channels would not cause an observable change.

An axoaxonic synapse where the release of NT from the primary synapse is increased. this occurs through facilitating the synapse by increasing Ca entry into it.