GIRK

• shortcut pathway
• SA node Cell
• ACh activates a GPCR and the betagame subunit goes off to activate a k channel, allowing K to leave the cell
• this hyperpolarizes the cell to slow down heart beat
• alpha subunit creates cascade that closes IF and calcium channels

PKA

• 2 catalytic domains and 2 regulatory domains 
• need 4 cAMP to bind with the two regulatory domains to change the conformation to active
• PKA phosphorylates proteins with ATP (Ca chanels)
• protein phosphatase dephosphorylates things

PLC

Dopamine D1 and D2

• D2 uses Gi GPCR
• D1 uses Gs GPCR

Signal Amplification

• receptor to Gprotein
• not gprotein to AC
• AC to cAMP
• not cAMP to PKA
• PKA to phosphorylation

Excitotoxicity

• overload of Ca through NMDARs
• too much glutamate release (from damaged neurons) causes excessive calcium influx
• causes cell death(excitotoxicity) through apoptosis from Ca activating caspases

Biological Toxins

• botulinum toxin: bacteria, blocks ACh release
• Tetrodotoxin(TTX): pufferfish/fugu, blocks sodium channels (action potentials and thus transmission)
• botulinum toxins destroy SNARE protein(syntaxin, SNAP-25, synaptobrevin
• tetanus toxin destroys synaptobrevin

Myasthenia Gravis

• synapse abnormality
• normal presynaptic terminal
• post synaptic terminal has reduced nAChR on muscle cells
• synaptic cleft is wider and junctional folds are shallower
• all lead to less response, reduced transmission
• autoimmune disease against nicotinic receptors
• ptosis, eyelids effected
• AChE inhibitors(edrophonium, neostigmine) can relieve ptsosis

Spike Initiation Zone (SIZ)

• initial segment of axon hillock
• where action potential is initiated or not
• highest voltage gated Na channel density and lowest AP threshold(most negative)

Spatial vs temporal Summation

of EPSPs 

• temporal: one input(A) activated in successation(same input different time) and the inputs will summate (time)
• spacial summation: more then one input at different locations at the same time or different times (length)
• responses summate in axons with long time constants (and length)
• short time/length do not have enough time to summate

Passive Properties of Neurons

• resting membrane resistance(larger cell, smaller R)
• larger cells have more ion channels open at rest(smaller resistance)
• membrane capacitane(larger cell, larger C)
• axial resistance of processes(larger process, smaller Ra)
• same current will produce a greater EPSP(V) in a smaller cell

Minature spontaneous synaptic response

(mini)

• most of time release of content from single vesicle
• response very small
• quantal analysis is compareing responses to miniature to determine number of vessicles released

Types of Synaptic plasticity

• short term: activity dependent strengthening or weakening of chemical synapses which lasts for up to a few minutes
• long term: activity-dependent strengthening or weakening of chemical synapses which lasts from hours to years

Short term synaptic plasticity

• seconds to minutes
• synaptic facilitation: if another action potential comes when some Ca still left in terminal, then more Ca comes in and more neurotransmitter is released (difference in amplitude)
• synaptic depression: reduction of NT if two + AP invade the terminal and the pool of vessicles depletes
• synaptic potentiation and augmentation: 

Long term synaptic plasticity

• hours to years
• long term potentiation (LTP): 
• Long term depression (LTD): 
• LTP and LTD can occur only on the dendritic spines
• LTP or LTD occur independently on individual synapses of a neuron

Long Term Potentiation

(LTP)

• LTP is triggered by high stimulation rate(more than 10 stim/s)
• during high frequency stim, strong depolarization causes silent NMDA receptors to be permeable for Ca via removing Mg block from the receptor, leading to LTP (hippocampus, uses AMPA)
• this increases effectiveness of existing postsynaptic AMPA receptors via phosphorylation(early or fast phase of LTP)
• late phase LTP is the expression and insertion of additional AMPA receptor
• increasing of the presynaptic NT release via retrograde signaling

Induction of LTD

(hippocampus)

• LTD is triggered by low stimulation rate (about 1 stim/s) (low levels of intracell Ca)
• under weak depolarization, NMDA receptor channel is blocked by Mg preventing Ca influx
• low concentration Ca activates protein phosphatases(during LTP, the kinases are activated)
• protein phosphatases dephosphorylate AMPA receptors restricting their efficiency(postsynaptic responses become smaller)

Long Term Depression (LTD)

Cerebellum

• climbing fibers activate Voltage gated Ca channels
• parallel fibers activate AMPA receptors9depol due to an influx of Na
• parallel fibers activate metabotropic receptors(2nd messenger-activating prtotein kinase C)
• LTD occurs when all three intracellular signals occur at the same time ^^^^^
• purkinje cells are inhib, therefore when their activity is suppresed by LTD, these neurons provide less inhib to their target cells, making the targets more excited