Neurotransmission Flashcards
properties of synaptic transmission
- rapid transmission
- integration of info
- summation of info
- adaptable, dynamic
- plasticity, changes neural pathways
- important for memory and learning
describe basic structure of a neurone
dendrites with spines lead to a soma (cell body) leaving the soma is an axon which ends in nerve terminals.
spines are membranous protrusions of the dendrites which contain synaptic proteins. These are where synapses occur and each dendrite has many spines.
what are dendrites
where information is received on a neurone
between neurones what kind of transmission occurs?
chemical, it only takes around 2ms, VERY FAST
where does neurotransmission occur?
at the synapse. Presynaptic terminal releases neurotransmitter, which diffuses across 20-100nm gap, then binds to postsynaptic membrane receptors, triggering a response.
what would you see under microscope when looking at an asymmetric synapse?
vesicles primed for exocytosis in presynaptic terminal. post synaptic density, full of proteins like receptors and proteins that help binding of neurotransmitter.
what are the 3 stages of synaptic transmission?
1) biosynthesis, packaging, release of neurotransmitter
2) receptor action
3) inactivation of response
types of neurotransmitter
Amines
Amino acids
Neuropeptides
examples of amino acid neurotransmitter
glutamate (major STIMULATOR in CNS)
glycine
GABA
examples of amine neurotransmitter
Noradrenaline
Dopamine
example of a neuropeptide
opioid peptides
what diversity is there in neurotransmitter action
- differ in speed of effects (micro seconds to milliseconds)
- vary in abundance
multiple transmitter effects are integrated to provide a wide variety of functional responses
how is neurotransmitter release triggered?
Action potential depolarises presynaptic membrane which triggers VGCCs to open. influx of calcium causes exocytosis.
how is the transmitter recycled?
actively pumped back into the presynaptic bouton or glial cell after usually being broken down by enzymes.
how are vesicles primed and released at the synaptic terminal?
vesicles containing neurotransmitter are primed on the cytoplasmic leaflet of the presynaptic membrane.
vesicle proteins interact with the membrane proteins in the active zone holding it in place so that when an AP arrives there is rapid release.
this vesicle complex contains synaptotagmin, a calcium sensitive protein, which changes conformation when calcium binds. hence fusion and exocytosis of neurotransmitter.
vesicles then refill.
vesicular protein complexes are targeted by neurotoxins give examples
TETANUS causes paralysis
BOTULINUM causes flaccid paralysis
(These causes transmitter not to be released)
LATROTOXIN (spider) stimulates transmitter release to depletion so cannot reform.
how do receptor kinetics affect how fast transmission is?
ionotropic receptors have fast stimulatory or inhibitory transmission (eg nicotinic receptors)
GPCR needs triggering of enzyme which is slow (eg muscarinic in PNS and dopamine receptor in CNS)
action of the glutamate receptor
opens sodium channel allowing influx of Na+. leading to an EPSP, excitatory post synaptic potential
action of Pentameric GABA Receptor
allows inlfux of chloride which hyperpolarises membrane hence is inhibitory as threshold is raised for response. (IPSP)
action of glycine receptor
influx of Cl-
types of glutamate receptor
AMPA Receptor, which open in response to glutamate allowing allows influx of Na+. these are rapidly onset.
NMDA receptors have slower onset, only work if cell has already been depolarised and allow Ca2+ and Na+ influx, these serve as coincidence detectors (in learning/memory processes).
what does the NMDA receptor do?
influx of calcium and sodium, slow onset, only opens after cell already depolarised. this causes phosphorylation of AMPA receptors allowing more Na+ conductance and transcription to make new synapses occurs. this means next time a stimulus triggers neurotransmitter release, the response will be greater. this contributes to memory and learning.
how is glutamate synthesised and reuptaken?
synthesised from the TCA cycle,
reuptake occurs using an EAAT, excitatory amino acid transporter back into the presynaptic terminal itself or a CNS Glial cell which forms glutamine using glutamine synthase.
what causes epilepsy?
abnormal firing of post synaptic membrane due to excess of glutamate in synapse or decreased levels of GABA. this leads to seizures.
what is a seizure?
transient alteration in behaviour due to disordered synchronous rhythmic firing of brain neurones
types of seizure
partial, originating from one side of the brain
generalised, involving both parts of the brain
manifestation arises from which part of the brain is associated:
absence
tonic - clonic
myoclonic
atonic
How is GABA synthesised?
from glutamate from TCA cycle, Glutamic acid decarboxylase converts glutamate to GABA.
How is GABA re-uptaken into glial cells and the presynaptic terminal?
using the GABA Transporter (GAT). in glial cells, GABA is then converted into succinyl semialdehyde using GABA transaminase.
how to anticonvulsants/antiepileptics generally work?
increase amount of GABA (inhibitory) in the synapse
how does phenobarbital and diazepam work?
enhances conductance of Cl- by promoting GABAR action
how does vigabatrin work?
inhibits GABA transaminase
how does Tiagabine work?
blocks the GABA Transporter
