Synaptic Transmission.txt

• An action potential depolarizes the axon terminal
• The depolarization opens voltage-gated Ca2+ channels and Ca2+ enters the cell
• Calcium entry triggers exocytosis of synaptic vesicle contents
• NT diffuses across the synaptic cleft and binds with receptors on the postsynaptic cell
• NT binding initiates a response in the postsynaptic cell
• **there’s a relationship btw the vesicle and Ca2_ channels. Ca2+ ch’s are held right next to where the vesicle is being held, so that Ca2+ doesn’t have to diffuse very far to allow the vesicle to be released --- therefore, the protein in the vesicular membrane that recognizes Ca2+ doesn’t have to have very high affinity because you have a very high local Ca2+ concentration. In this way, get a very localized effect

Voltage-gated calcium channels initiate synaptic transmitter release

• Sodium channels: generate the action potential depolarization
• Potassium channels: induce recovery hyperpolarization in action potential
• Calcum channels: initiate synaptic transmitter release and muscle contraction

• To be able to get rid of the NT form the cleft quickly to allow for another firing to occur
• Can fatigue neurons because need to also allow time for vesicles to be endocytosed and recycled back to the surface – docked and ready to go

• Opens cation (Ca/K/NA) channels = EPSPs
• Acetylcholine – neuromuscular junction
• Glutamate in the CNS

• Opens chloride channels = IPSPs
• GABA: brain
• Glycine: spinal cord

• Slow synaptic NTs
• Acetylcholine, Glutamate, GABA, and probably glycine

• Anxiety: Benzodiazepines promote an increase in channel openings by increasing affinity for GABA
• Myesthenia gravis: Inhibition of acetylcholine esterase promotes action o acetylcholine at the neuromuscular junction
• Parkinson’s disease: L-dopa increases supply of dopamine for synaptic release
• Depression: Selective serotonin uptake inhibitor (SSRI) increases neurotransmitter levels at synapse

M2 lines pore and is important because it changes the size of the pore

• Need two Ach molecules to bind
• This make the protein more sensitive – won’t just open spontaneously, need a certain minimum concentration to make two, rather than just one molecule of Ach bind and activate channel

• 3-TM subunits
• Receptor made from 4 subunits
• NMDA receptors
• AMPA receptors
• Some glutamate can feed back to act on metabotropic receptors and suppress pre-synaptic Ca channels and decrease further release of NT

With rapid firing, before all of the NT in the cleft has degraded away, might have addition of two stimuli, and produce a greater response than to the same stimulus when start with baseline

If apply stimulus, and get closer to, but don’t quite reach threshold value, and then apply a second stimulus that’s the same, might be able to get to the set threshold and get an actual response!

• 1. Three excitatory neurons fire.
• 2. Their graded potentials synapsed on the same cell body, for example, arrive at trigger zone together and sum to create a suprathreshold signal.
• 3. An action potential is generated
• Inhibition: one inhibitory and two excitatory neurons fire; the summed potentials are below threshold, so no action potential is generated

• One type of ionotropic glutamate receptor
• Glutamate comes in, sodium channels open, calcium channels open, calcium rushes in through the Ca channel BUT magnesium can “clog” the channel. If inside of the cell is slightly depolarized, however, K+ and it’s charge will make the Mg “pop out” of the channel and allow the channel free to let Ca to pass through. Glycine, which is normally inhibitory NT, Glutamine receptor needs to bind glycine as well.

• The two receptors have different responses
• And if just one is activated, might not get an actual, full expected response
• A neuron if has both becomes a co-incidental detector: need to bet 2 different stimuli before actually get response
• Hebbian synapse: a Co-indicent detector

• Hyppocampus: high frequency stimulation activates both AMPA and NMDA receptors, a rise in postsynaptic calcium, prolonged activation of kinases (CaMKII and PKC).
• This leads to insertion of more postsynaptic AMPA receptors: and possibly presynaptic increases in transmitter release

• Low frequency activation of NMDA receptors or metabotropic glutamate receptors leads to removal of postsynaptic AMOA receptors, perhaps activating protein phosphatases
• Get formation of silent synapse

A subunit of the receptor changes when mice go from juvenile to adult, but if make it so adul mice have the juvenile subunit, mice retain novel object memory better

• Glutamate spillover in ischemic stroke and traumatic brain injury
• Glutamate Excitotoxicity
• Calcium overload hypothesis implicates NMDA receptors
• NMDA blockers prevent short-term neurotoxicity but exacerbate long-term toxicity. This may depend on NR2 subtype. Also, uncompetitive antagonists such as memantine may only block pathologically high glutamate levels
• NMDA receptors may also be involved in neurodegeneration of Alzheimer’s Huntington’s, and Parkinson’s diseases