Building a nervous system Flashcards
What do electric synapses do?
Connect heart muscle fibres - vital for cardiac function
More common in NS than previously thought, but role is unclear
They can propagate action potentials through channels that are able to pierce both the synaptic bouton and dendrite, connecting both cells as if they were one cell, so that the AP can pass straight through
What do chemical synapses do?
Great majority of synapses in vertebrates
Many types with many roles
Target for neuro-active chemicals
These release neurotransmitters into the synaptic cleft, which then bind to receptors on the post-synaptic membrane
How are neuropeptides synthesised?
Synthesised using protein making machinery within the cell body
They can be transported to the synaptic terminal via the cytoskeleton of the axon
How are catecholamines synthesised?
They can be synthesised locally, in the synaptic terminal itself
How are neurotransmitters packaged?
Axons ‘bite’ off a bit of their synaptic membrane, and use it to package the neurotransmitter into synaptic vesicles.
These vesicles are then held to the pre-synaptic membrane by proteins
What triggers the release of neurotransmitters?
Depolarisation - usually because of arrival of action potential
The release of the neurotransmitter is Ca2+ dependent
An AP causes the VgCC to open, allowing calcium to diffuse into the presynaptic membrane
Calcium attaches to the proteins holding the vesicle to pre-synaptic membrane, and triggers them so that they drag the vesicle into the presynaptic membrane, allowing the vesicle to fuse with the membrane, releasing the neurotransmitter into the synaptic cleft.
The neurotransmitter will then attach to the post-synaptic receptors
How are neurotransmitters removed from the synaptic cleft?
NT must be removed to clear synapse, so that synapse can continue to respond to incoming action potentials
Some peptides are able to just diffuse out of the synaptic cleft, where they are removed by non-specific peptide degrading processes.
Ach and MAO for example, are broken down via enzymatic degradation. Enzymes attached to the other membranes can break down the neurotransmitter.
Some neurotransmitters can be reuptaken into the synaptic terminal (these re-uptake transporters are alpha-2 receptors), and they can be repackaged and reused.
Fast neurotransmitters such as glutamate and GABA, are taken back into astrocytes (glia), where they break the neurotransmitters up, and then send them back to the synaptic terminal where they can be used again
Describe the transmission that occurs at ligand-gated (ionotropic) receptors
What neurotransmitters can bind here?
- Fast, time-dependent transmission
- Signalling molecules that acts as ligands bind to binding sites of ligand-gated receptors, causing the opening of the VgNa channels, allowing depolarisation inside the cell, producing excitatory postsynaptic potentials
NTs = Glutamate (CNS), Ach (NMJ)
Describe the inhibition of action potentials at ligand-gated (ionotropic receptors)
What neurotransmitters can bind to these receptors?
- Ligand (In particular GABA) binds to VgCl channels, causing these to open, allowing chloride ions to enter the cell
- For APs to be inhibited, chloride ions must enter a cell, as they are anions and, therefore, increase the negativity inside the cell, leading to more polarisation (hyper polarisation) of the cell, inhibiting the action potential.
- This is then know as an inhibitory postsynaptic potential (ipsp)
- NTs = GABA, glycine
Describe metabotropic (modulatory) receptors and their effects
What neurotransmitters can bind to these receptors?
- Slow, non-time dependent effects
- Have a receptor molecule with neurotransmitter binding site, but has no channel within it
- Instead there’s an active site on the inside, which then activates a G protein embedded within the membrane
- Activated G proteins can have multiple functions such as:
- Opening and closing protein channels
- Producing secondary messengers (intracellular signalling molecules) - These messengers can open and close ion channels, or they can diffuse into the cell where they can trigger other things, such as protein synthesis
- Metabotropic receptors tend to produce diverse, subtle effects, so they don’t depolarise or hyperpolarise a cell, but rather they adjust how the cell responds to its incoming fast synaptic inputs
- NTs = Dopamine, Ach, serotonin, NA
What is the main structural difference between ionotropic and metabotropic receptors?
Ionotropic receptors contain ion channels, allowing for the flow of ions in or out of the cell
Metabotropic receptors have a large protein with a binding unit for a neurotransmitter, which then activates a G protein embedded within the cell membrane, and this G protein can then activate ion channels, or release intracellular messengers (secondary messengers)
Why do therapeutic drugs have selective effects?
There are many steps in synaptic transmission:
- Production + packaging NT
- Depolarisation and opening of VgCC for Ca2+ entry
- Ca2+ triggers exocytosis of NT
- NT binds to receptors
- Receptors activate + produce postsynaptic effects
- NT removed from cleft and hence receptors
- Receptor action terminate
Drugs can be designed to target any of these steps, so pharmacological manipulation allows for events in a synapse to be altered
There are many different neurotransmitters, and each can act on different types of receptors.
In this way, different neural pathways use different combinations of transmitter and receptor
Drugs that target different types of synapse have selective effects on different pathways
What is synaptic plasticity?
Surviving nerve cells recircuited/rewired (undergo adaptive changes) to have new functions, resulting in the strengthening or weakening of synaptic connections
Describe LTP and what happens when a single synapse is activated, and when a group of synapses are activated
- Long-term potentiation
- LTP is important for learning, as it’s the basis for laying down memories
- Effects fast-excitatory synapses
- Strengthens effective synapses
- Weakens useless synapese
- This allows it to create a more effective neural circuit
If a single synapse activates on its own:
- Produces tiny depolarisation, not very effective
- The more often this happens, the weaker the synapse becomes and it loses its machinery, so will eventually stop being used
If a group of synapses are activated:
- Activate all at the same time, as they’re all taking part in a single circuit, so are driven by the same processes
- Their inputs summate - they join together to strongly depolarise the cell
- These synapses become stronger, as the post synaptic cell sends messages back letting the LTP know that that was an effective synapse
- These synapses then gain machinery to make transmitters, release transmitters and gain more receptors, so that the next action potential is stronger
- The singular synapse does not receive more support, so becomes weaker
What are the specific conditions under which a synapse potentiates?
Synaptic bouton releases glutamate just before postsynaptic cell strongly depolarises
This is important for the LTP, as glutamate helps neural communication, memory formation, learning and regulation
