Lecture 1 Synaptic transmission Flashcards
what is a synapse
a specialised junction where part of a neuron contacts and communicates with another neuron or cell type (muscle or glandular)
what are the two main categories of synapses
chemical (majority) and electrical (minority)
how do electrical; synapses compare to chemical
simpler structure and function faster passive signal transmission bidirectional minority (common in development) allow synchronised electrical activity among populations of neurons
how do chemical synapses work simply
Arrives as electrical and converted to chemical and back to electrical in chemical synapses
what is a drug
a chemical substance, which when administered to a living organism, produces a biological effect
drugs affect how signals are communicated at a synapse
eg caffeine
affects learning and memory
what are the types of synapse
axodendritic
axosomatic
axoaxonic
what is the presynaptic element
upstream neuron, source of current
what is the postsynaptic element
downstream neuron, into which current flows
how does synapse location link to function
where they are affected how strongly they affect the postsynaptic neuron
what is an axodendritic synapse
presynaptic axon to dendrite in postsynaptic neuron
what is an axosomatic synapse
presynaptic contact to postsynaptic soma (more synaptic weight)
what is an axoaxonic synapse
presynaptic axon contacts axon of another cell before attaching to postsynaptic soma, affects communication as can cancel each other out (signal integration to determine excitation/inhibition)
what is the chemical synapse
synaptic bouton - presynaptic element
cytoskeleton - aid function and passing signals
mitochondria
synaptic vesicles - cont nt
synaptic granules ^
active zone - membrane of presynaptic cell to optimise conditions of membrane for communication
synaptic cleft - gap btwn AZ and postsynaptic cell
what is the neuromuscular junction
similar to chemical synapse
one synapse innervates many muscle fibres
vesicles contain Ach, received by muscle fibres converted to electricity for contraction
what is the postsynaptic membrane at the neuromuscular junction called
motor end-plate
folds to inc SA for more powerful reception of signals
how does synaptic transmission occur
as an action potential reaches the synaptic terminal, nt molecules are released from presynaptic neuron and diffuse across cleft to post synaptic membrane
what do receptors on the postsynaptic membrane recognise
specific neurotransmitters to initiate a response
what are the types of responses
direct excitatory or inhibitory (on or off) neurotransmission
neuromodulation - lots of possible effects (dynamic so important in development and memory)
what is direct excitatory or inhibitory transmission
the membrane of the next cell becomes slightly depolarised (ex) or hyperpolarised (in)
what is neuromodulation
alters the presynaptic cell’s ability to release more transmitter or the postsynaptic cell’s ability to respond
how much transmitter is released
released in specific packages (quanta)
what criteria define a neurotransmitter
synthesised in the neuron
present in presynaptic terminal and released to exert a defined effect on postsynaptic neuron or effector organ
administered exogenously it mimics action of endogenously released transmitter
specific mechanism exists to remove it from cleft
what is the first step of typical chemical synapse transmission
transmitter synthesised then stored in vesicles
what is the 2nd step of typical chemical synapse transmission
action potential invades the presynaptic terminal
what is the 3rd step of typical chemical synapse transmission
presynaptic. terminal depolarises causes opening voltage gated ca2+ channels
what is the 4th and 5th step of typical chemical synapse transmission
influx of Ca2+ causing vesicles to fuse with presynaptic membrane
what is the 6th and 7th step of typical chemical synapse transmission
transmitter released int synaptic cleft by exocytosis
binds to receptor molecules in postsynaptic membrane
what is the 8th and 9th step of typical chemical synapse transmission
opening or closing of postsynaptic channels
postsynaptic current causes ex or in potential that changes the excitability of the postsynaptic cell
what is the 10th and 11th step of typical chemical synapse transmission
remove nt by glial uptake or enzymatic degradation
retrieve vesicular membrane from plasma membrane
where and how are vesicles anchored in the presynaptic cell
pool of vesicles anchored to cytoskeleton by synapsin
how does action potential flow through the cell
action potential to presynaptic terminal, voltage gated ca2+ channels open so ca2+ flows to cytoplasm activate calmodulin activated kinase II (CaMKII) which phos synapsin
How are synaptic vesicles released and recycled
activates calmodulin activated kinase II (CaMKII) which phos synapsin
P-synapsin can no longer bind to cytoskeleton, allows vesicles to dock to active zone to start fusion/exocytosis
vesicles reused
what is a SNARE complex
at active zone
enzyme (ATPase) docks vesicles to plasma membrane as a helical protein with v and t SNAREs
what are the mechanisms of exocytosis during neurotransmitter release
vesicle docks
entering Ca2+ allows binding to membrane
SNARE complex form to pull membranes together
entering Ca2+ binds to synaptotagmin
ca2+ bound synapto catalyses membrane fusion by binding SNAREs to plasma membrane
how are vesicles recycled
rapidly recovered by endocytosis (10-20 sec), new vesicles bud off and refilled with transmitter
whole cycle about 1min
how are SNARE proteins affected by clostridial toxins
sites of proteolysis blocking nt release
target amino acids in SNAREs
botox and tetanus prevent transmission release
how does botulinum toxin affect SNAREs
stops neuromuscular transmission of Ach - paralysis by relaxation (treatment for muscle paralysis)
how does tetanus toxin affect SNAREd
interneurons at spinal cord, GABA/gly to stop inhibitors - permanent contraction
where are botulinum and tetanus toxins from
from bacteria Clostridium botulinum and tetani respectively
what diseases affect the presynaptic terminal
cong myasthenia syndromes - impaired vesicle recycling
latrotoxin - trigger vesicle fusion
botox and tetanus
cog disorders impair transsynaptic signalling
LEMS attacks presynaptic Ca2+ channels
how are vesicular transporters powered
proton gradient
ATPase proton pump loads up vesicles with H+ to make acidic (pH 5.5 comp to cytoplasm 7.2)
eg 1 glut traded for 1 H+ (counter transport)
how are plasma membrane transporters powered
by electrochemical gradient
Na+ higher outside and K+ inside
eg glut co transported in with 2 Na+
what do glia do
part of tri-partite synapse - support and regulate
support synaptic transmission
express nt receptors (can respond to synaptic activity by changing intracellular Ca2+)
coordinate synapse formation and elimination with secreted and cell surface associated signals
what do glia control
synapse formation function plasticity elimination crucial in development, learning, memory and disease
how do glia link to disease
reactive gliosis post injury (relevant to CNS regeneration)
aberrant synapse formation (link to epilepsy and neuropathic pain)
brain cancer
HIV induced dementia
neuroinflammatory response (depression)
neurodegernative diseases (Alzheimers, glaucoma, prion disease through aberrant synaptic stripping)
