Transmission in the CNS Flashcards
What is the range of number of synapses a single neurone can make?
Where in the brain is the neurone that has the single largest number of recorded synapses?
- A neurone can make anywhere from 1 synapse to 10,000 + synapses.
- The neurone with the single largest number of recorded synapses (10,000) is in the cerebellum.
What are dendritic spines?
Dendritic spines are protruding regions along the length of a dendrite that allow for synaptic connection with other neurones.
*Looks like lots of small bumps on the dendrite processes.
What is cotransmission?
What is the purpose of cotransmission?
- Cotransmission is the use of multiple different neurotransmitters at a single synaptic terminal.
- This allows for more complex modes of communication - the synapse can either be stimulated to release one or multiple of the neurotransmitters involved in cotransmission.
What is a neuromodulator?
How does it differ from a neurotransmitter?
- A neuromodulator is a signalling molecule that adjusts the activity of another neurotransmitter.
- Neuromodulators cannot drive synaptic activity on their own, whereas a neurotransmitter can.
- Neurotransmitters are like on/off light switches, whereas neuromodulators are like light dimmers.
Describe the structure of the GABAA receptor.
Why is this useful for drug design?
The GABAA receptor has 5 subunits:
- 2x alpha.
- 2x beta.
- 1x gamma.
- Each subunit has its own variant, meaning there are many subtypes of GABAA receptors.
- This is useful for drug design because subtypes of receptors are distributed among the brain in different quantities and in different regions. This means that a specific region of the brain can be targeted by targeting the subtype of receptor that is predominant in that brain region.
To which receptor does benzodiazepine bind?
To which region of this receptor does benzodiazepine bind?
What effect does benzodiazepine have at this receptor?
- Benzodiazepine binds to the GABAA receptor.
- It binds to an allosteric site of the GABAA receptor.
- Here, it has a neuromodulatory effect (can’t drive activity on its own).
What is coactivation / coagonism?
Give an example of coactivation / coagonism.
- Coactivation / coagonism is the requirement of multiple neurotransmitters binding to a receptor to cause receptor activation.
- For example, glycine is required as well as glutamate to activate NMDA receptors.
What are mosaics?
Why is this useful for drug design?
- Mosaics are clusters / ‘rafts’ of multiple different adjacent receptors.
- These receptors can influence the downstream effects of their neighbouring receptors, meaning a ‘dirty’ drug can be designed to target multiple receptors in one mosaic to produce a stronger effect.
What is volume transmission?
Where is volume transmission particularly common?
- There are neurotransmitter receptors external to synapses, e.g. on the exterior surface of a dendrite / axon and also on some glial cells.
- If too much neurotransmitter is released into a synapse, the neurotransmitter can spill over into the extracellular space, where it can stimulate these extrasynaptic receptors. This is known as volume transmission.
- Volume transmission is also more likely to occur with particular neurotransmitters, namely noradrenaline and dopamine.
- Volume transmission is the norm in the PNS (partially because the PNS commonly uses noradrenaline) but is less common in the CNS.
How does the location of a synapse influence its electrical effect on the postsynaptic neurone?
The closer a synapse is to the soma of the postsynaptic neurone, the greater its excitatory / inhibitory effect.
How do synapses appear on an electron micrograph?
Why?
Why is this useful for drug design?
- Synapses appear as large black smudges on electron micrographs.
- These black smudges represent clusters of proteins that serve as anchoring systems / scaffolding for the synaptic receptors.
- This is useful for drug design because these proteins can be targeted to influence the position of synaptic receptors and modify mosaics.
List 3 ways by which retrograde transmission can occur.
Retrograde transmission can occur by:
1 - Autoreceptors on presynaptic terminals providing feedback to the output neurone.
2 - Retrograde messengers released by the presynaptic terminal.
3 - Dendritic release of neurotransmitters from the postsynaptic terminal back to the presynaptic terminal.
List 2 functions of retrograde transmission.
Functions of retrograde transmission include:
1 - Trophic signalling.
2 - Influencing synaptic strength.
