Neurotransmission Flashcards
What is neurotransmission`/
Communication of information between neurons in the brain
What is the function of neurons?
To communicate information.
Give an example of the function of neuron communication
Maintaining homeostasis
What is a synapse?
A specialised junction where transmission of information takes place between a nerve fibre and another nerve, or a muscle of gland.
Loewi’s demonstration of chemical neurotransmission
Where the vagus nerve of an isolated frog’s heart was stimulated, the heart rate decreased (upper panel). If the perfusion fluid from the stimulated heart was transferred to a second heart, its rate decreased as well (lower panel).
Neurotransmission substance requirements
- The substance must be present within the presynaptic neuron.
- The substance must be released in response to presynaptic depolarization, and the release must be Ca2+-dependent.
- Specific receptors for the substance must be present on the postsynaptic cell.
What does demonstrating the identity of a neurotransmitter at a synapse require?
Showing
- It’s presence
- It’s release
- The postsynaptic presence of specific receptors
What is action potential?
The electrical signals in neurons that convey information from the brain to organs
Central nervous system synapses process
- Action potential reaches axon terminal of presynaptic neuron
- Ca2+ enters synaptic knob (presynaptic axon terminal)
- Neurotransmitter is released by exocytosis into the synaptic cleft
- Neurotransmitter bind to receptors that are an integral part of chemically gated channels on subsynaptic membrane of posysynaptic neuron
- Binding of neurotransmitter to receptor opens that specific channel
What are the three types of neuronal communication?
- Chemical transmission*
- Electrical transmission*
- Ephaptic transmission
Whats involved in ephaptic transmission?
Where two axons are so close together that the current produced by one has a major effect on the adjacent axon
What does wiring transmission require?
Requires close contact with specialised sites within neurons
What does volume transmission require (not)?
Does not require specific connections between cells. It is a slower and less specific form of neurotransmission.
How do neurotransmitters move by in volume trasnmission?
- Diffusion through the blood stream
- Cerebral Spinal Fluid (CSF)
What is the release of neurotransmitter involved in volume transmission?
Extrasynaptic release of chemical messenger (neurotransmitter)
What is chemcial transmission?
Communication between neurons that involves the rapid release of a chemical messenger that diffuses across to the receiving cell and causes a change in the postsynaptic cell’s properties.”
Where does chemical transmission occur at?
Synapse
How is information transmitted in a chemical synapse?
Form of chemical message
Give the basic details of chemical transmission
- Synthesis and storage of neurotransmitter
- Conduction of action potential down the axon of a neuron
- Opening of voltage-gated Ca2+ channels
- Release of transmitter into the synaptic cleft
- Activation of postsynaptic receptors
- Breakdown/ reuptake of neurotransmitters
Give the ‘biochemical’ details of chemical transmission
- Transmitter is synthesized and then stored in vesicles.
- An action potential invades presynaptic terminal.
- Depolarization of presynaptic terminal causes opening of voltage-gated Ca2+ channels.
- Influx of Ca2+ through channels
- Ca2+ causes vesicles to fuse with presynaptic membrane.
- Transmitter is released into synaptic cleft via exocytosis
- Transmitter binds to receptor molecules to postsynaptic membrane
- Opening of closing of postsynaptic channels
- Postsynaptic current causes excitatory or inhibitatory postsynaptic potential that changes the excitability of the postsynaptic cell.
- Retrieval of vesicular membrane from plasma membrane
What are neurotransmitters?
Chemicals that are released at a synapse by the presynaptic neuron and consequently affect the postsynaptic cell in a specific manner
What are the three main categories of neurotransmitters?
- Amino acids
- Peptides
- Monoamines
What is acetylcholine involved in?
Voluntary movement of the muscles
What is glutamate involved in?
Major excitatory neurotransmitter, roles in memory and learning
What is dopamine involved in?
Motivation, pleasure associated with addiction and love
What is serotonin involved in?
Emotions, wakefulness and temperature regulation
What is GABA involved in?
The major inhibitory neurotransmitter
What do neurotransmitters bind to and what does this cause?
Bind to specific postsynaptic receptors, causing either excitation or inhibition of postsynaptic neuronal activity.
What are neurotransmitters stored in?
In synaptic vesicles
What is the purpose of neurotransmitters being stored in synaptic vesicles?
- Protect from enzyme degradation
- Ready for release
What are the types of vesicles?
- Small clear-core vesicles (50 nm diameter)
- Large, dense core vesicles (100 nm)
What are small clear-core vesicles triggered by?
Triggered by single action potentials (low MW neurotransmitters)
What are large dense-core vesicles released by?
Burst firing or repetitive stimulation (bioamines and neuropeptides)
Name the small molecule transmitters.
- Acetylcholine
- Amino acids
- Purines
- Biogenic amines
Name the peptide transmitters.
- Substance P
- Opioids
- Somatostatin
- Vasopressin
Give the details of small-molecule transmission
- Synthesis of enzymes in cell body
- Slow axonal transport of enzymes
- Synthesis and packaging of neurotransmitter
- Release and diffusion of neurotransmitter
- Transport of precursors into terminal
Give the details of peptide transmission
- Synthesis of neurotransmitter precursors and enzymes
- Transport of enzymes and pre-peptide precursors down microtubule tracks
- Enzymes modify pre-peptides to produce peptide neurotransmitter
- Neurotransmitter diffuses away and is degraded by proteolytic enzymes
What do action potentials do to synaptic terminals?
Action potentials depolarise synaptic terminals
What happens when action potentials depolarise synaptic terminals?
Voltage-sensitive Ca+ channels are opened
What is involved in docking in presynaptic vesicles?
Movement of vesicle from reserve pool to tight association with plasma membrane
What is involved in priming in presynaptic vesicles?
Reactions that convert the vesicle to a form that can fuse in response to an action potential
What is involved in fusion in presynaptic vesicles?
Local elevation of calcium concentration stimulates vesicle to fuse with membrane
What are the steps that occur in presynaptic vesicles?
- Docking
- Priming
- Fusion
What are postsynaptic receptors?
Transmembrane proteins that bind released neurotransmitters.
What the neurotransmitter bind to?
the binding site of a specific postsynaptic receptor
What does the neurotransmitter binding induce?
A conformational change and opens an ion channel directly or indirectly.
What does the opening of ion channels on the postsynaptic cell cause?
A change in the excitation of the cell.
What do activated receptors cause?
Brief electrical responses called “synaptic potentials
What are metabotropic receptors linked to?
Indirectly linked to the ion channel by G-proteins and second messenger cascades
Give examples of metabotropic receptors
- Metabotropic glutamate receptors
- Muscarinic acetylcholine receptors
- Dopamine
- Most serotonin receptors
Give the details of metabotropic receptors
- Neurotransmitter binds
- G-protein is activated
- G-protein subunits or intracellular messengers modulate ion channels
- Ion channel opens
- Ion flow across membrane
Give examples of ionotropic receptors
- Nicotinic acetylcholine receptor
- Glutamate receptors (e.g.. AMPA, NMDA and kainate receptors)
What are the visual symptoms of the grinning death?
- Risus sardonicus
- Opisthotonus
- Trismus
What is tetanus toxin?
An extremely potent neurotoxin produced by the vegetative cell of Clostridium tetani
What is the journey of tetanus?
- Initially binds to peripheral nerve terminal and transported within axon and across synaptic junction until reaches CNS
- Fixes to gangliosides at presynaptic inhibitory motor nerve endings then taken up into axon by endocytosis
- Blocks release of inhibitory neurotransmitters (GABA and glycine)
- If nerve impulse unchecked by inhibition lead to unopposed muscular contraction and spasms.
What does tetanus toxin block (and what does this lead to)
Blocks glycine leading to spastic paralysis
Name a cosmetic type of neurotoxin
Clostridium botulinum
What occurs in stimulation in myasthenia gravis?
Decrease in amplitude with repeated stimulation because fewer muscle fibres in motor unit are firing action potentials
What is muscle contraction hindered by in myasthenia gravis, and what does this prevent?
Hindered by IgG autoantibodies which prevent acetylcholine from binding to NMJ
Onset of myasthenia gravis
Onset is slow precipitated by emotional stress, hormonal imbalance (thyroid disturbance), infection/vaccination, trauma, surgery, temp. extremes and excessive exercise
What does myasthenia gravis lead to?
Fluctuating muscle weakness and fatigability.
What does myasthenia gravis treatment include?
Anticholinesterases, immunotherapies (chronic and rapid) and thymectomy.
Give the details of postsynaptic responses
- Neurotransmitters bind to receptors, which change the ion permeability of the postsynaptic plasma membrane
- Activation of receptors cause postsynaptic potentials that can be excitatory (EPSPs) or inhibitory (IPSPs)
- PSPs from dendrites spread passively and converge on the cell body
If PSPs are above the threshold potential, an action potential will arise
What is the chemical initiatior of the cerebral cortex?
Glutamate
What is glutamate?
The principle excitatory neurotransmitter in the vertebrate nervous system
What does the activation of postsynaptic ionotropic glutamate receptors
Causes a transient opening of ion channels allowing net influx of cations, generating an excitatory current
What do metabotrophic glutamate receptors play a role in?
Play a modulatory role in synaptic transmission
What does glutamate play a role in?
Plays a role in learning, memory etc. as well as various disorders (e.g. epilepsy, schizophrenia, brain damage etc.)
Details of glutamate as a neurotransmitter
- The molecule must be synthesized and stored in the presynaptic neuron
- The molecule must be released by the presynaptic axon terminal upon stimulation
- The molecule must produce a postsynaptic response
- There must be a mechanism for
inactivation
Where are AMPARs and NMDARs localised? (mostly)
Mostly e co-localised at glutamatergic synapses where they mediate ‘fast’ chemical synaptic transmission
What can NMDARs, AMPARs and KainateRs be (synaptic)?
- Can be both synaptic and extrasynaptic
- Can be both pre-synaptic (autoreceptors) and post-synaptic
Where are glutamate receptors mainly localised to?
Postsynaptic receptors
What is AMPAR localisation by?
By fluorescent antibodies
What are glutamate receptors mainly localised to?
To dendrites of the postsynaptic cell
What are the two common morphological types of glutamatergic synaptic connection in the brain?
- When the postsynaptic neuron is excitatory, the glutamatergic synapse can be on spine or shaft.
- When the postsynaptic neurons is inhibitory, the glutamatergic synapse can be on the soma of the neuron or shaft.
What do dentrites often posses and give function?
Dendritic spines, which typically receive synaptic inputs from one presynaptic axon
What do dendritic spines contain?
Postsynaptic densities (PSDs)
What do PSDs contain?
- Glutamate receptors
- Associated and auxiliary proteins
- Signaling molecules required for neuronal activation
What do dendritic spines increase?
Increase the synaptic efficiency of the neuron
What are dendrite spines connected to the main dendritic shaft by?
By a thin neck
Give the details of ionotropic receptors (iGluR)
Fast transmission, Ions flow in/out of neuron, Millisecond responses.
Give the details of metabotropic receptors (mGluR)
Slow synaptic transmission, Activation of second messenger cascades, Seconds for responses to arise
Give journey of ionotropic receptors (iGluR)
- Neurotransmitter binds
- Channel opens
- Ions flow across membrane
Give journey of metabotrophic receptors (mGluR)
- Neurotransmitter binds
- G-protein is activated
- G-protein subunits or intracellular messengers modulate ion channels
- Ion channel opens
- Ions flow across membrane
Give two methods of measuring neuronal responses
- Voltage Clamp Experiments
- Current Clamp Experiments
Describe voltage clamp experiments
Artificially control membrane voltage, and measure ionic current flowing across the membrane required to maintain the voltage
Describe current clamp experiments
Inject current (via a microelectrode) to a neuron and measure the change in the membrane potential.
What do non-NMDA receptors generate?
Generate the large and early component of EPSCs
What do NMDA receptors contribute to?
Late component of the EPSCs
Name two non-NMDA receptors
- AMPA
- Kainate
AMPA receptors
a-amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid receptors
What are AMPARs responsible for?
Most of the fast excitatory synaptic transmission in the central nervous system
Why are AMPARs responsible for most of the fast excitatory synaptic transmission in the central nervous system?
As they open and close quickly
What are AMPARs permeable to?
- Sodium
- Potassium
- To a smaller extent, calcium
What are AMPARs formed as a combination of?
GluA1,GluA2, GluA3 and GluA4
What can AMPAR activity be potentiated and regulated by?
Second messenger cascades of PKA, PKC, CaMKII
What do the four subunits of AMPARs combine to form?
Tetramers
What are AMPARs composed of?
GluA1
GluA2
GluA3
GluA4
What does each AMPAR have?
4 glutamate binding sites (one in each subunit).
When an the AMPAR channel be opened?
When two or more sites are occupied by glutamate (or an agonist)
