synapse

sir charles scott sherrington

experimented for concept of synapse, coined synapse/neuron, (import)

hwo did shrrington conduct his research

found that neurons communicate by studying spinal reflexes

3 concepts of synapse sherrington found

reflexes are slower than conduction along axon, weak stimuli happen at different times, as one set of muscles relaxes, another becomes excited.

excitatory postsynaptic potential (EPSP)

graded potential (depolarization) decays over time from opening NA channels

inhibitory postsynaptic potential (IPSP)

temporary hyperpolarization of neuronal membrane (brake), when synaptic input opens a protein channel for K to leave

what did otto loewi do

demonstrated that synapse use chemical transmitters

7/8 events at synapse

synthesis, transport/storage, release, receptor binding, seperation from R, reuptake, feedback

3 classes of molecules for synaptic comm

fast, neuromodulatory, hormones

fast NT

rapid effects, mediated at site of release

neuromodulatory NT

less rapid, work to modulate activity at synapse

hormones

slow and broad in their effects

synthesis (step 1)

neurons synthesize Nt from metabolic intermediaries

transport/storage (step 2)

NT’s synthesized in presynaptic terminal and held there

release (step 3)

vesicle hold NT, exocytosis (release NT into synaptic cleft)

what is dependent on the release of NT at terminal

a Ca++ influx, from AP spreading into terminal and acting on v-sens Ca++ channels

key details about release of NT

neurons release at least 2 or more transmitters, (less than milliseconds), respond to many types of NT when released

coexistence principle

neurons and synapses have 1 NT and many co-NT (neuropeptides), 1NT + co-NT per synapse

key component of coexistence principal

NS achieves complexity by diversity of postsynaptic receptors

receptor binding (step 4)

has two class of receptors (ionic and metabotropic)

ionic receptors

responsible for fast EPSP and IPSP (Na oe Cl channel)

metabotropic receptors

activate G protiens, slower receptors/last longer (GPCR)

seperation (step 5)

Nt will unbinf from receptor after postsynaptic receptor is activated

reuptake (step 6)

when presynaptic neuron retrieves Nt for later, use transporters (membrane proteins)

feedback (step 7/8)

autoreceptors or retrograde signals

what are autoreceptors in feeback

NT receptors on presynaptic terminal that may have future release

what are retrograde signals in feedback

directed/moving backward from post to presynaptic neuron

glutamate (FAST)

main fast NT in CNS, most forebrain structures use this, has 3 ionotropic (iGluRs)

iGluRs

AMPA, NMDA, kainate (all have Na channel

GABA (FAST)

main inhibitory NT in CNS w/ 2 main receptors

GABA receptors

GABA-A-ionotropic opens Cl channel for fast IPSP, GABA-B- metabotropic slower for IPSP by opening K channel

acetylcholine (NEUROMODULATORY)

nicotinic and muscarinic

nicotinic

ionotropic (excitatory) in skeletal muscles/brain)

muscarinic

GPCR (exciatory/inhibatory) in PNS/CNS

Nucleus Basalis of Meynert

key ACh, makes cell groups that supply ACh to forebrain/cortex

Pedunculopontine & laterdorsal tegmental nuclei

2 key ACh, make cell groups in midbrain that supply to caudal part

dopamine (NEUROMODULATORY)

5 types (D1-D5)

D1/D5

excitatory class, stim production of second messengered (cAMP)

rest of D’s

D2 part of inhibatory class, rest inhib production of cAMP (2 types of domaminergic neurons)

2 dopaminergic neurons

ventral tegmental area and substantia nigra

norephinephrine (NEUROMODULATORY)

4 types (aplhpa1/2, beta1/2) all GPCR

locus coeruleus

cell group for making NE

beta blockers

at on beta receptors

serotonin (NEUROMODULATORY) (5-HT)

19 subtypes, all GPCRs

raphe nuclei

5-HT cell groups (dorsal raphe nucleus most forebrain), antideppressants act on this

peptides/others (neuromodulatory)

neuropeptides (cotransmitters), gases like NO act as retrograde signal