19.5 Synaptic Transmission Flashcards
Where are peptide neurotransmitters assembled? Give examples of such neurotransmitters
Synthesised in the rough ER and split in the Golgi Body
Buds off the Golgi body in vesicles which are transported to the membrane
Oxytocin, vasopressin
Which types of receptor generally lead to fast transmission?
Ionotropic Glutamate EPSPs
Ionotropic GABA A receptors IPSPs
Which types of receptors lead to slow transmission? Why?
Metabotropic receptors such as the adrenergic, opioid, and GABAB receptors.
NK1-3 G protein coupled peptide receptors = slow EPSP
Involve changes in the cells metabolism (metabotropic) and second messengers take longer to act
Which is the fast or slow EPSP?
Temporal summation
Two EPSPs are elicited and nervous cell membrane is able to store charge
Presynaptic action potentials are happening in quick succession
What type of summation is shown below?
Spatial summation
Neuron is receiving more than one input so EPSPs summate
Charge spreads out (space constant)
Excitatory postsynaptic potential (EPSP)
A depolarising potential in the postsynaptic neuron; increases probability of postsynaptic neuron firing action potential.
Inhibitory postsynaptic potential (IPSP)
Inhibitory hyperpolarisation of postsynaptic membrane; decreases probability of postsynaptic neuron firing action potential
Synaptic integration
The process by which multiple EPSPs and/or IPSPs combine within one postsynaptic neuron, in some cases triggering one or more action potentials
Pre-synaptic inhibition
Inhibitory neuron fires onto axon terminal of a presynaptic neuron, reducing the amount of neurotransmitter it can release
Main inhibitory NT in CNS
GABA
Main excitatory NT in CNS?
Glutamate
What are the main classes of neurotransmitter in the CNS?
- Amino acids
- Acetylcholine
- Monoamines
What are some examples of amino acid neurotransmitters in the CNS?
- GABA
- Glutamate
- Glycine
What are some examples of monoamines neurotransmitters in the CNS?
- Catecholamines (noradrenaline, dopamine)
- Indoleamines (5-hydroxtryptamine a.k.a. serotonin)
- Others (melatonin, histamine)
What is the criteria to be established as a ‘neurotransmitter’?
- Localised in neurons, and specific to one or more neuronal lineage(s).
- Secreted by neurons.
- Able to activate synapses and be mimicked
How can it be proven that a neurotransmitter is localised in a neuron?
Antibody-staining and immunocytochemistry are generally the best methods to determine this, although looking for the activity of certain enzymes can also be used
How can it be proven that a potential neurotransmitter is actually secreted by neurons?
This can be shown through the detection of constant levels proportional to number of cells when neurons are incubated, and it should be possible to induce release (shown by an increase in concentration in the medium) through processes such as electrical stimulation
How can it be proven that a neurotransmitter can be mimicked?
This can be shown through application of an exogenous source of candidate neurotransmitter to neurons in the absence of the endogenous molecule, or through use of agonists/antagonists for pharmacological interventions that change its ability to stimulate neurons downstream
Approximately what percentage of neurons in the brain are utilising these neurotransmitters:
- Glutamate
- GABA
- Other
- Glutamate -> 60%
- GABA -> 30%
- Other -> 10%
What neurons use glutamate as a Where are glutamate receptors and neurons found in the CNS?
- Cortico-cortical neurons
- Cortico-subcortical neurons
Summarise the synthesis, release, reuptake and recycling of glutamate at a synapse.
- Synthesis starts with glutamine, which is converted to glutamate by glutaminase
- VGLUT1 or 2 or 3 is the transporter that packages the glutamate into vesicles (in exchange for H+)
- Upon an action potential, the calcium flux causes release of the vesicle contents into the synapse
- Na+-dependent transporters reuptake the glutamate into the pre-synaptic neuron and other cells (such as glial cells)
- In glial cells, glutamine synthase is used to produce glutamine again, which is shuttled back to the pre-synaptic neuron using glutamine transporters (SN1/SN2 and then SATs)
What are the different types of glutamate receptor?
[IMPORTANT]
Ionotropic:
- AMPA (use Na+ currents)
- NMDA (use Ca2+/Na+ currents)
- Kainate (use Na+ currents)
Metabotropic:
- mGluR1-8 (lead to rise in IP3)
What is the effect of stimulating ionotropic glutamate receptors?
They trigger a mixed fast EPSPs:
- First, AMPA receptors trigger a fast-onset depolarisation
- This depolarisation releases a voltage-dependent Mg2+ block on the NMDA, which allows further depolarisation
What is the effect of stimulating metabotropic glutamate receptors?
There are 8 different types of mGluR:
- Some lead to slow excitatory effects
- Some lead to slow inhibitory effects
Therefore, the effect depends on the particular synapse.
What are some putative functions of glutamate as a NT in the brain?
[IMPORTANT]
It is the main excitatory NT in the CNS:
- Memory -> Mediates LPT (long term potentiation: a persistent increase in synaptic strength following high-frequency stimulation of a chemical synapse)
Explain this graph
The NMDA receptor transmits Na+ like the AMPA receptor across the membrane but can also carry Ca2+ in addition to this, so while it may take longer for it to respond to stimulation by glutamate and its agonists, the depolarising response is greater as a result of the influx of divalent ions.
Why is the inward ionic current of NMDA receptors said to be ‘voltage dependent’?
At a normal negative resting potential Mg2+ ions clog the pore preventing other ions from flowing through
Mg2+ leaves the pore when the membrane is depolarised (generally after activation of neighbouring AMPA channels)
NMDA is transmitter gated and volatge dependent