Lecture 6- Synaptic Transmission Flashcards
How are signals sent between neurons
Neurotransmitter release
How are signals received within a neuron
Postsynaptic signalling machinery
What did Leowi first demonstrate in the 1920s and how
-Chemical transmission
-Fluid from a donor heart to recipient slowed down heart rate
Types of synapses
-Axodendritic
-Axosomatic
-Axoaxonic
What is the most common type of synapse
Axodendritic
Process of classical neurotransmitter synthesis
-Dietary precursors cross the BBB
-Enzymes in the axon terminals synthesise classical NTs and pack them into vesicles
-Classical NTs remain in vesicles, don’t readily cross membranes
Neuropeptide transmitters are synthesised where
In the cell body (nucleus)
Forms of classical neurotransmitters
-Amino acids
-Monoamines
-Acetylcholine
Forms of non classical NTs
-Lipids
-Neuropeptides
-Gases
Neuropeptide containing vesicles are transported where
Down the axon
NTs are transported into vesicles via
Proteins called vesicular transporters
Vesicular transporters are vital for
Determining neuronal phenotype
Process of action potential
-Voltage gated Ca2+ channels open
-Ca2+ influx
-Activation of CaM Kinase II
-Phosphorylation of proteins
-Proteins move vesicles to release site
-Fusion of vesicles and exocytosis
Vesicles fusion with the cell membrane is mediated by
-SNARE
-SNARE complexes form to pull membranes together
-Ca2+ binds to synaptotagmin, catalysing membrane fusion
Opening of a fusion pore is a target for
Various toxins
Effects of botulinum toxin
-Cleaves and prevents Fusion complex formation at NM junction
-Affects SNARE protein
-Does not release NTs
Do NTs target specific receptors
-No
-Significant spill over of NTs at many synapses, reaching receptors at other synapses
-Can activate not targeted synapses
In the cerebellum, spillover of NTs can
Give rise to slow rising EPSC
Regulation of NTs release
-Rate of AP
-Probability of transmitter release
-Autoreceptors
Somatodendritic does what
Regulates firing
LSD is an agonist at
5-HT1a AR, which can slow down rate of firing
Autoreceptors vs Postsynaptic receptors
-Autoreceptors are receptors on the same neuron that’s releasing NTs
-Autoreceptors modulate activity of cell depending on location
Transporters blockade increases
Transmission
Transporters suck up NTs into
Presynaptic terminal
Enzymes in synaptic cleft and terminal rapidly
Degrade NTs
Are synaptic terminals reliable
-No
-Only 10-20% of action potentials trigger release
Steps of fast synaptic transmission
-Synthesis, transport and storage
-Depolarisation
-Open voltage gated Ca2+ channel
-Ca2+ influx, activate CaMKII and phosphorylate proteins
-Movement and docking of vesicles
-Exocytosis-diffusion
-Interact with receptors
Nomenclature of terminal depends on
Type of transmitter released
Most receptors that are acted upon are embedded in
The cell membrane
Ionotropic receptors
-Ligand gated ion channels
-Fast, allows ions to pass
Metabotropic receptors
-G protein coupled receptors
-Slow use second messengers
Ligand gated channels (ionotropic receptors)
-Made of multiple subunits bound together
-Ions flow down electrochemical gradient
What is the agonist and antagonists for acetylcholine receptor
-Agonist: nicotine
-Antagonist: curare
GABA A receptor features
-When activated, opens so chlorine ions pass through
-Agonist: GABA, alcohol, BDZ
-Antagonists: Picrotoxin
G protein coupled receptors (GPCRs) (metabotropic receptors)
-Single proteins with several transmembrane domains
-Indirectly influence cell activity
-Receptor coupled to an intracellular effector
-Over 90% are in the brain
Two ways to alter cellular functioning via G proteins
-G protein is coupled to a messenger system
-Some are directly coupled to an ion channel
Second messengers activate
Protein kinases which in turn activates other second messengers via phosphorylation
How does cAMP work
-Gs activates and Gi inhibits adenylate cyclase
-Converts ATP into cAMP
-This activates proteins or remove phosphate groups
Drugs of abuse differentially activate
Kinases compared to non drugs of abuse
What is pERK
-ERK that has had a phosphate group added
-High levels found in nucleus accumbens after addictive drugs
Second messengers can alter gene
Regulation or transcription (DNA to mRNA)
Features of glutamate
-Fast chemical signalling
-Most important excitatory NT in the brain
-All neurons have receptors for glutamate
Changes in glutamate signalling appear to be major mechanisms for
Learning and memory
vGLUTs package
Glutamate into vesicles
EAATs take up
Glutamate from the synaptic cleft
Glutamate receptors are both
-Ionotropic and metabotropic
-Found pre and post synaptically
Receptors located on dendrites
-AMPA
-NMDA
AMPA receptor features
-Fast excitatory transmission
-Only has sodium pass through it
-AMPA is the only agonist
NMDA receptor features
-Slow excitatory transmission
-At rest -70 mV
-Has a magnesium blockade
-When magnesium is removed, neuron is depolarised at +40
-Calcium and sodium can flow
-NMDA is the only agonist for the NMDA receptor
Strong stimulation induces waves of
Gene expression
Effected IEGs have
-Direct effects on synaptic function or intracellular signalling
Arc once induced becomes
-A protein
-Stops the signalling of AMPA receptors through internalising them
What does MAP kinase phosphate do
Removes phosphate from pERK as a negative feedback function
Drugs of abuse can robustly induce
IEG expression
IEGs are a marker of what
Activity
If you have fos going up
You have arc going up, there is activity
True or false, psychomotor sensitisation is likely to occur with closely spaced psychostimulant injections
False
Amphetamines are still used legally today to test weight loss and narcolepsy
False
Classical neurotransmitters
-GABA
-Glutamate
-Dopamine
What do terminal auto receptors do
Regulate neurotransmitter release
Protein kinase activation can elicit
-Activation of transcription factors which results in mRNA expression
-Alteration of cytoskeletal proteins and cellular morphology
