L10- Neuromodulation and synaptic integration Flashcards
What are 3 possible mechanisms for altering the efficacy of synaptic transmission?
- Pre-synaptic: amount of NT released per AP
- Post-synaptic; response of receptor to NT
- Post-synaptic: excitibility of postsynaptic cell
What are retrograde NT and signals?
Neurochemical released by postsynaptic neurone which then modulates function of presynaptic neurone
Give an example of retrograde signalling?
Endogenous cannabinoids are released in reponse to postsynpatic Calcium influx.
Then feedback modulated presynaptic NT release via effects on the Calcium channels in the PRE synaptic membrane.
Endocannabinoid goes back and changes presynaptic.
Name 4 allosteric modulators of GABAa receptor?
1.Barbituates- CNS depressant. Anti- anxiety, anti convulsant (epilepsy).
Increased duration of GABA channel opening. Means more inhibition.
2.Benzodiazepines- sedative, anti-anxiety, anti-consulvant. Increased frequency of GABA channel opening– so more inhibition.
What do barbituates do?
Barbituates- CNS depressant. Anti- anxiety, anti convulsant (epilepsy).
Increased duration of GABA channel opening. Means more inhibition.
What do bensodiazepines do?
Benzodiazepines- sedative, anti-anxiety, anti-consulvant. Increased frequency of GABA channel opening– so more inhibition.
What is an example of postsynaptic neuromodulation in a mammalian hippocampal neurone?
Noradrenline increases excitability of postsynaptic cell.
Noradrenaline-> cAMP-> closes K+ channels in postsynaptic membrane.
WHat is synaptic integration?
Where PSPs are summed on the postsynaptic cell. add up
What do IPSPs do?
Take membrane potential further from the threshold. Inhibit.
What are PSPs?
graded electrical signals
Where is the final decision made about whether to fire an AP?
At action potential initiation zone. At the axon hillock. It has high density of VSNa channels so a low threshold.
How do graded PSPs travel to the axon hillock?
In a passive decremental fashion. Inputs furhter away from the axon hillock have less influence on final output.
Why is the location of the synapse key?
Further from axon hillock, the weaker the signal is when it reaches it.
What does the spread of a PSP along the membrane depend on?
- time constant τ (tau
- length constant λ
- diameter
- membrane resistance Rm
- internal resistance Ri
1 and 2 are of the membrane
3,4,5 are of the dendrite. Dendritic cable properties.
Which dendritic cable properties affect the spread of PSP along the membrane?
diameter, membrane resistance, inernal resistance
What is the length constant? λ
The distance over which PSP travels to reach 37% of its original size.
What is the time constant (tau)
The time taken for the PSP to decay to 37% of its peak value
What can temporary ichanges in the Rm via gated ion channels lead to?
Rm = membrane resistance.
leads to Changes in passive spread of PSPs.
What does synaptic integration involve?
Summation of EPSPs and IPSPs on the postsynaptic membrane.
Axon hillock acts as a read-out if the membrane is above the AP threshold
What is spatial summation?
A few post-synaptic neurones coming together on post synaptic neurone. Their APs add up to enough to fire an AP>
What is temporal summation?
APs fired frequently on presynaptic neurone. Enough to reach threshold.
What is shunting inhibition?
An inhibitory synapse, located close to the soma, can switch off all other inputs to that dendrite.
What is a disease which shows the importance of inhibition in the CNS?
Hyperekplexia; Startle Disease.
Jumping Frenchmen of Maine.
Single AA mutation in the glycine receptor- Cl ion channel. Inhibtion of the CNS is reduced. So get bigger shock.
What is AM and FM at the axon hillock?
AM- Graded PSP
FM- action potentials. ( AP either there or not.)
Which code do neurones use?
An FM code. The frequency and pattern of APs conveys information.