Synaptic Transmission (L1-3) Flashcards
What part of a dendrite do synapses terminate at?
The spines.
True or false? Dendrites are contacted by many axons therefore act to receive inputs.
True.
Name the initial segment of an axon.
An axon hillock.
What is the diameter range of an axon in humans?
1- 25 µm.
True or false? An axon cannot travel over a metre.
False. An axon can travel over a metre or more
What organism was the original experiment on the resting membrane potential conducted on?
A Squid.
What unit are membrane potential or membrane voltage represented by?
Vm.
What is the typical resting membrane potential?
-65mV.
How do voltage-gated channels detect a change in membrane potential.
Voltage-gated channels possess sensors that detect changes in membrane potential.
Describe the sequence of events of the cycle of an action potential. Describe the role of ion channels/gates.
- Voltage-gated Na+ and K+ channels are closed in resting state.
- A stimulus opens the activation gates of some Na+ channels depolarizing the membrane potential. If the threshold potential is reached, more Na+ channels open, triggering an action potential.
- Above threshold potential activation gates of all Na+ channels open. K+ channels begin to open.
- Na+ channel inactivation gates close and K+ channels are fully open. Efflux of K+ from the cell drops membrane potential back to and below resting potential. Both gates of Na+ channel are closed but K+ channels are still open.
- Continued efflux of K+ keeps potential below resting level.
Describe the absolute refractory period.
A period of complete resistance to stimulation, inactivation of Na+ channels means that after an action potential there is a brief period when no other action potential can be generated.
Describe the relative refractory period.
A period of partial resistance to stimulation. Lasts as long as the K channels are open. But strong stimuli can trigger new action potentials.
What is the conduction velocity of the peripheral nervous system?
20 AP/sec.
What is the conduction velocity of the cortex?
Up to 200-800 AP/sec.
Propagation speed depends on how local currents spread - which depends on what?
- Resistance of the axonal membrane
2. Internal resistance of the axon
The wider the axon the _____ the propagation speed and the _____ the internal resistance of the axon.
Faster.
Lower.
The _____ insulated the axon is the faster the propagation speed and the _____ the axonal membrane resistance.
Better/More.
Greater.
Define neurotransmission.
Communication of information between neurons in the brain.
Define action potential.
Action potentials are the electrical signals in neurons that convey information within the brain.
Define Wiring Transmission.
Neurotransmission that requires close contact with specialised sites within neurons.
Define Ephaptic Transmission.
Neurotransmission where two axons are so close together that the current produced by one has a major effect on the adjacent axon.
Define Volume Transmission.
Volume transmission is the diffusion through the Cerebral Spinal Fluid or blood of neurotransmitters released at points that may be remote from the target cells with the resulting activation of extrasynaptic receptors.
Define Chemical 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.
What is the width range of the synaptic cleft?
30-70nm.
Describe the stages 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.
Define neurotransmitters.
Neurotransmitters are chemicals that are released at a synapse by the presynaptic neuron and consequently affect the postsynaptic cell in a specific manner.
What are the 3 main categories of neurotransmitters?
- Amino acids
- Peptides
- Monoamines
Describe what function acetylcholine is involved in?
Voluntary movement of the muscles.
Describe Glutamate.
Major excitatory neurotransmitter, roles in memory and learning.
Describe what functions Dopamine is involved in?
Motivation, motor control, learning, memory and pleasure associated with addiction and love.
Describe what functions Serotonin is involved in?
Emotions, wakefulness and temperature regulation.
Name the major inhibitory neurotransmitter.
GABA.
What properties must neurotransmitters possess?
- The substance must be present within the presynaptic neuron.
- The substance must be released in response to presynaptic depolarisation, and the release must be Ca2+-dependent.
- Specific receptors for the substance must be present on the postsynaptic neuron.
- A biochemical mechanism for inactivation must be utilised.
Why are neurotransmitters stored in synaptic vesicles?
- Protection from enzyme degradation
- So they are ready for release
Name and describe the 2 types of vesicles.
- Small clear-core vesicles (50 nm diameter)
triggered by single action potentials (low
MW neurotransmitters). - Large, dense core vesicles (100 nm) released
by burst firing or repetitive stimulation
(bioamines and neuropeptides).
Name the small-molecule neurotransmitters.
- Acetylcholine
- Amino Acids
- Purines
- Biogenic Amines
Name the peptide neurotransmitters.
- Substance P
- Opioids
- Somatostatin
- Vasopressin
Describe Docking.
Movement of vesicle from reserve pool to tight association with plasma membrane.
Describe Priming.
Reactions that convert the vesicle to a form that can fuse in response to an action potential.
Describe Fusion.
Local elevation of calcium concentration stimulates vesicle to fuse with membrane.
Activated post-synaptic receptors cause brief electrical responses called _____ _____.
Synaptic potentials.
Define Ionotropic receptor.
A receptor protein that forms part of a ligand-gated ion channel, so that binding of a ligand to the receptor causes opening of the channel, permitting ions to flow through it.
Define Metabotropic receptor.
A receptor that is indirectly linked to the ion channel by G-proteins and second messenger
cascades .
Name 2 Ionotropic receptors.
- Nicotinic acetylcholine receptor
- Glutamate receptors
Name 4 Metabotropic receptors.
- Metabotropic glutamate receptors
- Muscarinic acetylcholine receptors
- Dopamine receptors
- Serotonin receptors
Describe the stages of Ionotropic receptor activity.
- Neurotransmitter binds
- Channel opens
- Ions flow across membrane
Describe the stages of Metabotropic receptor activity.
- Neurotransmitter binds
- G-protein is activated
- G-protein subunits or intracellular messengers modulate ion channels
- Ion channel opens
- Ions flow across membranes
Define a quanta.
The contents of one vesicle of neurotransmitter.
The size of synaptic potentials are _________ to the number of vesicles released and are multiples of quantum.
Proportional.
Each quantum gives the _____ postsynaptic response.
Same.
Single vesicles are released spontaneously and their postsynaptic response is called a what?
A “mini”.
A single CNS neurone may receive inputs from 100s of neurons. A decision to produce nerve impulses is made through the _______ of synaptic potentials impinging on a neuron. Once the threshold voltage is reached by _______, impulses are generated in an all-or-nothing manner.
Summation.
List the 4 ways to terminate a chemical signal.
- Enzyme degradation of neurotransmitter
- Reuptake by presynaptic neuron
- Binding of neurotransmitter to auto-receptor
- Diffusion of neurotransmitter by glial cells
Describe enzyme degradation of a neurotransmitter.
Transmitters are degraded by specific enzymes in the synaptic cleft.
Describe reuptake of neurotransmitters by the presynaptic neuron
Transmitters are pumped back into the
presynaptic bouton via specific reuptake proteins.
What does the binding of a neurotransmitter to an auto-receptor at a presynaptic membrane do?
Reduces exocytosis.
True or false? Neurotransmitters can be taken up and degraded by glial cells.
True.
Define desensitisation.
Progressive inactivation of a receptor due to the continuous presence of a transmitter.
Receptor desensitization results in altered affinity for the ligand, this can be accomplished by what 3 ways?
- Receptor phosphorylation
- Uncoupling of receptor effector molecules
- Receptor sequestration (internalization)
What does desensitisation do?
Desensitization modulates the shape of synaptic transmission, the activity of postsynaptic receptors and protects neurons from the neurotoxic effect of glutamate.
Electrical transmission is mediated by
specialised channels called _______.
Gap-junctions.
In electrical transmission how do neurons communicate?
Via direct contact between cells, allowing a direct passage of electrical current between one cell to the other.
Describe electrical synapses.
Electrical synapses are symmetrical, with no clear structural differentiation between pre and postsynaptic membranes.
In electrical transmission how far apart are the pre and post-synaptic membranes.
~3nm.
A gap-junction is formed of two ______ proteins from neighbouring neurons.
Connexon.
Connexons are formed of six membrane-spanning protein subunits called _______.
Connexins.
Connexons form pores which allow passage of solutes up to ____mw .
1500.
What is a faster mode of transmission, chemical or electrical? And by how much?
Electrical. Electrical transmission occurs in a
few microseconds - over a hundred times faster than in chemical synapses.
Gap-junction pore size can be modulated by:
- pH - (acidification closes)
- Ca2+ - (high calcium closes)
- Phosphorylation (phos. closes)
- Dopamine (high concs close)
What is the principle excitatory neurotransmitter in the vertebrate nervous system?
Glutamate.
What does glutamate play a role in?
Learning, memory, as well as epilepsy and brain damage.
Metabotrophic glutamate receptors play a ______ role in synaptic transmission.
Modulatory.
Describe the 2 common morphological types of glutamatergic synaptic connection in the brain.
- When the postsynaptic neuron is excitatory, the glutamatergic synapse arises in spine or shaft.
- When the postsynaptic neurons is inhibitory, the glutamatergic synapse arises on the soma of the neuron or shaft.
Excitatory dendrites often possess ______ ______, which typically receive synaptic inputs from one presynaptic axon.
Dendritic spines.
Describe the structure of dendritic spines.
A mushroom-like head connected to the main dendritic shaft by a thin neck.
True or false? Spines decrease the synaptic efficiency of the neuron.
False. Spines increase the synaptic efficiency of the neuron.
Spines contain machinery called the postsynaptic densities (PSDs). PSDs contain what?
Localised regions of glutamate receptors and
signalling molecules required for neuronal
activation.
Name the ionotropic glutamate receptors.
- NMDA-R (pre & post synaptic)
- AMPA-R
- Kainate-R (pre & post synaptic)
Name the metabotropic glutamate receptors.
- mGluR (pre synaptic)
- mGluR1
- mGluR2
- mGluR3
- VDCC (pre synaptic)
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.
Non-NMDA receptors (AMPA and Kainate
receptors) generate the large and ___1___
component of EPSCs, whereas NMDA-receptors contribute to the ___2___ component of the EPSCs.
- Early
2. Late
AMPA-Rs open and close quickly, and are thus
responsible for most of the ____ excitatory synaptic
transmission in the central nervous system.
Fast.
What are AMPA-Rs permeable to?
AMPA-Rs are permeable to sodium, potassium and to a smaller extent, calcium.
AMPA-Rs are formed of a combination of how many subunits? Name them.
- GluR1,GluR2, GluR3 and GluR4.
AMPA-R activity can be potentiated and regulated by second messenger cascades of what?
PKA, PKC, CAMKII and other unspecified kinases.
How many glutamate binding sites does each AMPA-R have?
- One in each subunit.
How many binding sites of AMPA-R must be occupied by glutamate (or an agonist) for the channel to open.
2 or more.
Most AMPA-Rs are either homo-tetramers of what?, or are ‘dimer of dimers’ which comprise what?
GluR1 or GluR4.
GluR2 and either GluR1, GluR3 or GluR4.
If the GluR1 or GluR4 gene of an AMPA-R is removed, then AMPA-receptor currents are ______.
Reduced.
Activation of NMDA-R requires binding of what?
Activation requires binding of glutamate and the co-agonist glycine.
NMDA-receptors allow the entry of which ions into the neuron?
- Ca2+
- Na+
- K+
True or false? AMPA-Rs and NMDA-Rs are both tetramers.
True.
List the 3 subunits of NMDA-Rs and the subtypes of each.
- NR1 - 8 splice variants
- NR2 - NR2A, NR2B, NR2C, NR2D
- NR3 - NR3A, NR3B
Which NMDA-R subunit contains a glycine binding site?
NR1.
Which NMDA-R subunit contains a glutamate binding site?
NR2.
Which NMDA-R subunit is responsible for the magnesium block?
NR2.
Which NMDA-R subunit reduces the inward currents?
NR3.
True or false? NMDA-Rs are ligand & voltage sensitive receptors.
True.
At resting membrane potential NMDA-Rs carry little current. Why?
Magnesium ions block permeability to cations.
In NMDA-Rs how is the magnesium block removed?
The magnesium block is relieved by depolarisation.
To function, NMDA receptors require what?
Glutamate, Glycine and a depolarised membrane
potential.
Calcium flux through NMDA-Rs is thought to play a critical role in what?
Synaptic plasticity (the cellular mechanism for learning and memory).
Activation of NMDA-R leads to what additional receptors being inserted into the membrane?
AMPA-Rs.
Metabotropic glutamate receptors (MGluRs) are ______ polypeptide chain proteins that bind glutamate.
Single.
Describe the structure of metabotropic glutamate receptors.
They have 7 transmembrane domains, with an intracellular C-termini and extracellular N-termini.
There are 8 subtypes of glutamate receptor that embody 3 distinct functional groups of glutamate receptor. mGlu1 & mGlu5 ____1____ synaptic function and the rest of mGlu1-8 _____2_____ synaptic function.
- Increase
2. Decrease
Describe group 1 mGluRs.
- Located on the postsynaptic termini
- Excitatory effect - increase synaptic function
- mGlu1 and mGlu5 subtypes
Describe the group 1 mGluRs pathway.
1) Glutamate binds to the group I receptor, which is coupled to PLC
2) Cleaves PIP2 into IP3 and DAG
3) IP3 diffuses to the cytoplasm and binds to ER which releases Ca2+
List the effects of activating group 1 mGluRs.
- Calcium release from stores = Calcium is implicated in synaptic plasticity. Calcium activates calmodulin causing synapse remodelling and synaptic vesicles mobilization
- PKC increase = phosphorylates a huge range of synaptic proteins, and enhances NMDA-receptor activity
- Homer protein released = Important for trafficking mGlu receptors into and out of synapses and functionally connect mGlu receptors to iGlu receptor
- Inhibition of K+ conductances = Increasing the excitability of neurons
- Less negative membrane potential = Increases the probablilty of action potentials arising in a neuron
Describe group 2&3 mGluRs.
- Mainly located on presynaptic terminals where they act as autoreceptors
- They reduce the amount of glutamate release from terminal
- Linked to Gi/o-linked GPCRs
Describe the group 2&3 mGluRs pathway.
- Group II or III mGluRs are negatively coupled to adenylyl cyclase - causing a reduction in intracellular levels of cAMP and PKA
- Reduces voltage-gated calcium channels in presynaptic neurons
- Dephosphorylation of proteins required in the signalling cascade for synaptic transmission
- May release GABA, an inhibitory neurotransmitter to decrease receptor activation
Define Excitotoxicity.
Excitotoxicity refers to the ability of glutamate and related compounds to destroy neurons by prolonged excitatory synaptic transmission (eg trauma or hypoxia-ischaemia).
Activation of mGlur groups 2 and 3 have a neuroprotective action by reducing what?
Presynaptic activity.
Define the Reversal Potential.
The membrane potential when the concentration gradient is exactly balanced by the electrical gradient.
Define Ohm’s law and give the equation.
Electric current is proportional to voltage and inversely proportional to resistance. V = IR.
GABAa, GABAc and glycine receptors are all what type of receptor?
Ionotropic Cl-.
The GABAb receptor is what type of receptor?
Metabotropic.
True or false? GABA and glycine receptors are all tetrameric structures.
False. They are all pentameric structures.
True or false? GABA and glycine receptors mediate fast inhibition.
True.
What do Benzodiazepines do to synaptic receptors?
Mediate sedation.
What do Barbituates do to extrasynaptic receptors?
Increase the affinity of GABA.
What do Neurosteroids do to extrasynaptic receptors?
Both positive and negative allosteric modulation.
What does alcohol do to extrasynaptic receptors?
Enhances GABA action.
