Synaptic Transmission Flashcards
What neurotransmitter is released at all post-ganglionic parasympathetic neurons?
ACh
What is another name for an electrical synapse?
Gap junction
What are 2 examples of electrical synapses in vertebrates?
-Cerebral cortex inhibitory neurons (often dendrodendritic)
-hippocampus (linking into other networks with electrical synapses)
Describe the structure of a gap junction
Comprised of 2 adjacent connexons (1 transmembrane in each cell membrane).
Connexon is comprised of 6 connexin subunits
What is an advantage of electrical synapses compared to chemical synapses?
Due to being electrically coupled, the time delay between depolarisation of adjacent cells is negligible, allowed neurons to synchronize activity
Describe the intracellular environment of a presynaptic terminal
-Lots of mitochondria
-secretory granules (having been transported soma along microtubules)
-Synaptic vesicles (full of NT)
How large is a chemical synapse?
The gap is ~5nm
What is notable about the post-synaptic membrane?
post-synaptic density - this is where all the receptors are localised
What are the “Classic” neurotransmitter types?
Amino acid or amine NTs
Where are classic neurotransmitters synthesised
All synthesis in the axon terminal
Describe the process of chemical synaptic signaling
- NT synthesised & stored in vesicles
- AP generated in presynaptic neuron, travelling to terminal
- Opening of voltage-gated Ca++ channels, influx of Ca++
- Ca++ causes exocytosis of vesicles
- NT released & diffuses across the synaptic cleft
- NT binds to receptors on the post-synaptic membrane
- Shutdown of transmission [ie enzymatic activity in synaptic cleft, or active transport into presynaptic terminal etc]
How much NT is contained per vesicle?
roughly ~200 molecules of NT HOWEVER this can be pharmacologically influenced
how many receptors can a single type of NT bind to?
A single type of NT can bind to many different types of receptors
What are 5 different CNS synapse morphologies and where you might find these?
Axodendritic [classic]
Axosomatic [many via gPCRs]
Axoaxonic [inhibitory NT system]
Axospinous [dynamic plasticity, learning & memory]
Dendrodendritic [many electrical synapses]
What type of synapse is this?
Axodendritic chemical synapse
What type of synapse is this?
Axosomatic chemical synapse
What type of synapse is this?
Axoaxonic chemical synapse
Give a common scenario with this synapse type and the role of each neuron
What is axon branching and an example of where this can be found?
When an axon splits to multiple terminals (to the same or different postsynaptic cell). Classical example is neuromuscular junction.
What ae the 2 types of synapses when categorised by membrane differentiation?
Gray’s type I: asymmetrical (large postsynaptic density), usually excitatory
Gray’s type II: symmetrical (pre & post synaptic densities equal), usually inhibitory
What are the 3 categories of neurotransmitter?
Amino Acid, Amines and Peptides
How many classic NTs are there?
9
What are the 3 Amino Acid type neurotransmitters?
GABA, Glutamate (Glu) and Glycine (Gly)
What is GABA?
Gamma-aminobutyric acid, major inhibitory NT in the brain
What is the role of Glutamate?
Major excitatory NT
What is the role of glycine?
inhibitory NT in the brainstem/spinal cord
What are the 6 Amine type NTs?
Acetylcholine (ACh)
Dopamine (DA)
Epinephrine
Histamine
Norepinephrine
Serotonin (5-HT)
How many NT types can a single neuron synthesise?
a single neuron will only synthesise a SINGLE classic NT (ie glutamergic will only ever be glutamergic) BUT many neuropeptides can be co-released
What NTs can cause rapid changes in the post-synaptic membrane potential and how?
-Amino Acid NTs (by opening ion channels)
-ACh (via nicotinic receptors)
-Serotonin (via ionotropic receptors)
[all other amine types only act through gPCRs]
What receptor types can bind with ALL classic NTs?
gPCRS (metabotropic receptors)
Describe the action of neuropeptides
- They are signaling molecules
-they all act at gPCRs
-all neuromodulators
-co-released with a “classic” NT
Where are neuropeptides synthesised and why?
At the Soma because it leverages the cellular machinery for peptide creation.
How do neuropeptides get to the terminal?
Once synthesised, gets packaged into secretory granules and actively transported to the terminal along microtubules
What is required for Classic NT synthesis?
Precursor molecule + synthesizing enzyme
Generally describe the process of NT release by exocytosis
- vesicle is docked & ready at the membrane
-AP arrives at the terminal
-VGCCs open
-influx of Ca++
-binds with docking protein & causes conformational change
-vesicle “dragged” to the membrane & binds
-NTs released into the cleft
What is the key mechanism of NT release?
Exocytosis is stimulated by intracellular [Ca++].
(There are many ways to increase [Ca++], not just VGCCs.
The [Ca++] is the key.
How many proteins are involved in synaptic vesicle release and recycling?
more than 30
Name the key proteins circled here
What is the function of clathrin?
protein in presynaptic terminal, coats the “used” vesicle
What is the function of dynamin?
protein in presynaptic terminal, “pinches” off the vesicle from the membrane (so it can be filled with NT)
What is the function of synapsin?
protein in presynaptic terminal, keeps filled vesicles together
What is the function of NSF & SNAPs?
proteins in presynaptic terminal responsible for priming of docked vesicles
what is the function of SNAREs?
Proteins in the presynaptic terminal, formed when a vesicle is primed & thought to be involved in fusion of vesicle to membrane
What is the function of synaptotagmin?
Senses Ca++ and pulled the vesicle into the membrane. It is the Ca++ sensor for exocytosis.
What processes in the presynaptic terminal are Ca++ dependent?
-Exocytosis of vesicles
-priming of vesicles
What are SNARE proteins comprised of?
-Synaptobrevin (on the vesicle membrane)
-syntaxin
-SNAP 25 (both on the pre-synaptic membrane)
Describe what happens to SNARE proteins with Ca++ influx
Ca++ influx causes synaptobrevin/syntaxin/SNAP-25 to form SNARE complex & vesicle is then primed & docked at the membrane
At the next Ca++ influx, synaptotagmin binds Ca++ & conformational change pulls the vesicle into the membrane
What is the result of synaptotagmin gene deletion?
Lethal mutation
Name each component in this diagram and the process being shown
What is the mechanism of botox & tetanus toxins?
They interfere with formation of SNARE complex and prevent release of NT
What is the structure of transmitter-gated ion channels?
5 transmembrane domains
What is a reversal potential?
The membrane potential where ionic current can reverse (ie go the opposite direction). This applies to generic channels ie ionotropic channels
What is the reversal potential?
For a single ion channel, Vr = equilibrium potential for that ion
If 2-ion channel, Vr = somewhere between the equilibrium potentials of the 2
What is EPSP
Excitatory post-synaptic potential - transient post-synaptic membrane depolarisation
What is IPSP
inhibitory post-synaptic potential - transient post-synaptic membrane hyperpolarisation
Describe the general steps of EPSP generation
-AP down the presynaptic neuron
-release of NT
-NT binds to post-synaptic neuron
-causes influx of Na+ in post-synaptic cell
-causes depolarising change in post-synaptic membrane potential (potentially moving closer to threshold for AP)
Describe the general steps of IPSP generation
-AP down pre-synaptic neuron
-release of NT
-NT binds to post-synaptic receptor
-causes Cl- influx in post-synaptic cell
-causes hyperpolarising change in post-synaptic membrane potential
**Note that we are NOT getting a Cl- flow at resting Vm, this would be in a cell that has already been depolarised - only then can we get IPSP using Cl- channel
What are the 2 types of post-synaptic receptors
ionotropic
metabotropic
Describe how gPCRs are neuromodulators
Because they will NEVER depolarise a membrane to threshold. They just make it easier or harder by moving Vm closer/further away from threshold.
What is the resulting action of gPCRs?
Activation of enzyme & second messenger systems, or G protein gated ion channels (indirectly open ion channel)
Describe autoreceptors and their function
- receptors on pre-synaptic axon terminal membrane (sometimes found on presynaptic cell dendrites)
-bind to the same NT that the neuron releases
-often inhibit further NT release (negative feedback loop)
-seem like a safety valve
What are 4 different ways to limit NT signalling & an example of each?
-Diffusion away from synapse [example - astrocytes uptake glutamate]
-Reuptake via active transport [SSRIs work by decreasing reuptake]
-Enzymatic breakdown in synaptic cleft [MAO inhibitors work by decreasing degradation in terminal]
-Desensitization to deactivate the NT [AChE cleaves ACh in cleft to render it inactive]
What is synaptic integration?
the process by which multiple synaptic potentials combine within one postsynaptic neuron
what is neural computation?
The processing of thousands of neural inputs
What is quantal theory?
how much NT has to be released to causes EPSP
What is quantal analysis?
The process of determining the number of vesicles that release during neurotransmission
What is the elementary unit of synaptic transmission?
synaptic vesicle
What is MEPP and what is the significance of it’s discovery?
Mini End Plate Potential - significance is that is suggests spontaneous release of NT vesicles that are NOT associated with depolarisation of pre-synaptic membrane - NOT due to calcium influx. This suggests they are “accidents” where vesicles randomly bumped into the membrane & released.
What is EPSP summation?
integration/adding together many EPSP to produce significant post-synaptic depolarisation
What are 2 ways of integrating EPSPs?
Spatial: multiple EPSP at SAME TIME but DIFFERENT locations
Temporal: Multiple EPSP in RAPID SUCCESSION at the SAME LOCATION
What is the active role of dendrites?
They actively shunt a potential towards the trigger zone using voltage gated channels
What are 2 examples of ways an IPSP can move Vm away from theshold?
-can bring in Cl-
-can take out K+
What is the result of pharmacological agents that block parasympathetic activity?
Blocking parasympathetic activity mimics sympathetic activity
What determines the effect of a released NT?
The receptor it binds to - receptor subtypes can cause different effects when binding to the same NT
What receptor subtypes does ACh bind to?
-nicotinic receptor
-muscarinic receptor
What receptor subtypes does norepinephrine bind to?
α receptor
β receptor
What receptor subtypes does Glutamate bind to?
AMPA
NMDA
Kainate
What receptor subtypes does GABA bind to?
GABA_A
GABA_B
Why is the active properties of dendrites important?
Because of signal decay in the cable model, spread of synaptic potential to the soma would be affected
How do inhibitory synapses shunt the synaptic current?
As an AP flows along a dendrite/axon, the inhibitory synapse can be generating an IPSP that prevents the AP flowing to the soma/axon hillock
