Lecture 3: Synaptic Transmission Flashcards
Tuesday 14th January 2025
What is a synapse?
Junction where information is passed
from one neuron to another (or to eg muscle)
Do some synapses clasp?
Yes
Describe electrical synapses
- Very close to each other, and no delay in the transfer of the signal, so very rapid.
- Can be two-way
- Has little plasticity
Describe chemical synapses
- Not right next to each other
- Delay in transmission of impulse by at least 0.5 ms
- One way
- Plastic (so can change properties and can change strength of trasmission)
Why is transmission between electrical synapses fast?
Because channels come together and form semi-permeable ion channels, which are permeable to ions and small molecules like dye. This formation of a gap junction results in rapid signalling.
What forms gap junctions in vertebrates?
Connexins
What forms gap junctions in invertebrates?
Innexins
What are some key features of a chemical synapse?
- Many mitochondira in pre-synaptic membrane to provide ATP for the movement of vesicles.
- Vesicles containing neurotransmitter
- Dendrite or dendritic spine in post-synaptic membrane
- The synaptic cleft is ~ 20-40 nm wide
What are the different types of chemical neurotransmitter?
- Amino acids: GABA (γ-amino butyric acid); Glutamate
- Amines: noradrenaline (norepinephrine); dopamine; 5-HT (5 hydroxytryptamine; serotonin)
- Slow Neuroactive Peptides: neurotensin
- Others: acetylcholine; nitric oxide; ATP
What happens when tissues are labelled with PS095?
Synapses in the tissues can be located
Where can synapses occur?
- On the dendron
- On the soma (cell body)
- On the axon
Do symmetrical synapses tend to be inhibitory?
Yes
Where is a non-peptide neurotransmitter synthesised?
A non-peptide neurotransmitter is synthesized in the nerve terminal and transported into a vesicle
Describe non-peptide neurotransmitter uptake
- Using ATP, H+ ions are pumped into the interior of a synaptic vesicle.
- The transporter uses this gradient to pump neurotransmitter into the vesicle
- The vesicle then fuses with the cell surface membrane and after neurotransmitter release, the vesicle membrane is retrieved so that the vesicle can be filled with neurotransmitter once again.
What can block the transport of H+ ions into vescicles?
Bafilomycin
Where are peptide neurotransmitters synthesised?
In the cell body. They are then transported to the terminals.
How do peptide nuerotransmitters reach the nerve terminals from the cell body?
They travel through the axon on microtubule tracks via fast axonal transport.
What are the 4 basic steps of neurotransmitter release?
- Docking/priming
- Influx of Ca2+ into the membrane
- Vesicle fusion (exocytosis)
- Recycling of vesicles (endocytosis)
Docking of vesicles to the membrane..
- A combination of SNAP and SNARE proteins anchor vesicles to the presynaptic membrane.
- Docked vesicles are primed and are ready to release their contents
- Ca2+ entry into nerve terminals
- The action potential…
- depolarises nerve terminal via voltage-gated Ca2+ channels
- opens voltage-gated Ca2+ channels
- Ca2+ moves into the nerve terminal down its electrochemical gradient into the neuron
Fusion of docked vesicles and neurotransmitter release
- Ca2+ binds to one of the SNARE proteins on their receptors
- This binding brings the 2 membranes together till they’re fused and a pore is opened.
- The neurotransmitter is then released through this pore.
What are some important features of Ca2+-dependent neurotransmitter release?
- Neurotransmitter release requires binding of multiple Ca2+ ions (between 3 to 5).
- Neurotransmitter release occurs very quickly after Ca2+ entry
- Blocking Ca2+ entry blocks synaptic transmission (cadmium and toxins from spiders/snails)
- Knockout of synaptotagmins: lose fast synchronous neurotransmitter release
Endocytosis (vesicle recycling)….
- Matrix is formed around the collapsed vesicle, which envelops the membrane and pinches the vesicle from the membrane.
What happens once neurotransmitter is released?
Once released, neurotransmitter binds to postsynaptic
receptors and produces cellular effects
What are the different types of receptor that can be present on the post-synaptic membrane?
- Channel-linked receptors (ionotropic).
- G-protein coupled receptors (metabotropic).
- Kinase-linked receptors
- Receptors linked to gene transcription (nuclear receptors)
Is it true that different receptors produce different speeds of signalling?
Yes
What is required for chemical synaptic transmission?
- neurotransmitter
synthesis (non peptide - locally - pre-synaptic terminal) - packaging
into vesicles - transmitter release
- Bind to receptors and post-synaptic affect
- Removal of neurotransmitter from synaptic cleft. (reuptake into neurones, extracellular metabolism, diffusion, uptake into glia cells).
How is acetylcholine synthesised?
- Requires acetyl-CoA, choline, and enzyme CHAT for synthesis.
-
What does CHAT stand for?
choline acetyltransferase
What transporter is used for packaging acetylcholine into vesicles?
Vesicular acetylcholine transporter (VAChT)
How many types of receptor can acetylcholine act as?
2
What are the 2 types of receptor that acetylcholine can act as?
Nicotinic (selectively activated by nicotine) and Muscarinic (selectively activated by muscarine)
Describe Nicotinic (selectively activated by nicotine)
Ionotropic
Permeable to Na+/K+
Fast signalling
Describe Muscarinic (selectively activated by muscarine)
Metabotropic
Second messenger cascade
Slower signalling
Are Fast and slow actions mediated by nicotinic and muscarinic ACh receptors, respectively?
Yes
How is acetylcholine broken down/removed?
- Broken down by enzyme acetylcholinesterase (AChE)
- Broken down into choline and acetate (inactive)
- Recycled by choline carrier in the neuron terminal membrane
How is a substance identified as a neurotranmsmitter?
- Must be synthesised in the neuron
- Show activity-dependent release from terminals
- Duplicate effects of stimulation when applied exogenously (outside of organism)
- Actions blocked by competitive antagonists in a concentration-dependent manner
- Be removed from the synaptic cleft by specific mechanisms
What is the evidence for acetylcholine as a neurotransmitter?
- Must be synthesised in the neuron:
The enzyme Choline Acetyltransferase (ChAT) is present in neurons and is responsible for making ACh. - Show activity-dependent release from terminals:
Vagusstoff - Duplicate effects of stimulation when applied exogenously:
Slows heart and contracts skeletal muscles - Be blocked by blocking drugs in a concentration-dependent manner:
Blocking receptors causes muscle paralysis - Be removed from the synaptic cleft by
specific mechanisms:
Presence of AChE and choline uptake carrier
Summary
- Synapses are site of the majority of chemical signalling within the nervous system
- They utilise a wide range of neurotransmitters and receptors
- This provides the nervous system with a wide range of ways in which the function of neurones and glia can be influenced
- Careful regulation of synaptic transmission ensures that synapses operate efficiently and within physiological limits
- Each of the stages of synaptic transmission can be affected by medicines or toxins, and some are sites of action of drugs of abuse
Transmission across synapses
from axon terminals (ends of cell) of one neurone to the dendrites (or soma) of the next neurone.
What are the different types of synapse?
Axospinous synapse – Axon terminal connects to a dendritic spine.
Shaft synapse – Axon terminal connects to the dendritic shaft (main branch).
Axosomatic synapse – Axon terminal connects directly to the soma (cell body).
Axoaxonic synapse – Axon terminal connects to another axon.
Axo-dendritic synapse – Axon terminal connects to a dendrite (not always labeled separately but shown here).
With a Axospinous synapse, where does the synapse occur?
Axon terminal connects to a dendritic spine.
With a Shaft synapse, where does the synapse occur?
Axon terminal connects to the dendritic shaft (main branch).
With a Axosomatic synapse, where does the synapse occur?
Axon terminal connects directly to the soma (cell body).
With a Axoaxonic synapse, where does an axon occur?
Axon terminal connects to another axon.
With a Axo-dendritic synapse, where does a synapse occur?
Axon terminal connects to a dendrite (not always labeled separately but shown here).
Peptide neurotransmitters are synthesised in the cell body and transported to the terminals. Peptide neurotransmitters include the opioid peptides (eg dynorphin, β-endorphin, enkephalins), Substance P, Neurokinin A & B, Neuropeptide Y.
Peptide neurotransmitters are synthesised in the cell body and transported to the terminals. Peptide neurotransmitters include the opioid peptides (eg dynorphin, β-endorphin, enkephalins), Substance P, Neurokinin A & B, Neuropeptide Y.
Clathrin-mediated endocytosis (CME)/ vesicle recycling…
- The membrane begins to invaginate (bend inward).
- Clathrin proteins coat the invaginating membrane.
- A vesicle buds off and is brought back into the neuron.
- This vesicle can then:
- Go directly back to the vesicle pool.
- Fuse with an endosome for further processing before recycling.
What are the different ways neurotransmitter can be removed from a synaptic cleft?
- reuptake into neurons
- extracellular
metabolism - diffusion
- cells uptake into glia
Is it true that at a synapse, the type of receptor on the post synaptic neurone determine how fast the signal is passed along?
Yes
Ionotropic Receptors → fast excitatory postsynaptic potential (EPSP)
Metabotropic Receptors → Slow EPSP
Acetylocholine acts as 2 types of receptors. it can act as a nicotinic receptor and as a muscarinic receptor. Please describe both of these receptors.
- Nicotinic (selectively activated by nicotine):
Ionotropic
Permeable to Na+/K+
Fast signalling - Muscarinic (selectively activated by muscarine):
Metabotropic
Second messenger cascade
Slower signalling
