Lecture 4 - inhibitory neurotransmission Flashcards
What do inhibitory interactions allow for in the brain?
information to be encoded more efficiently.
Explain what David Marr discovered.
The donut arrangement of each cell (centre spot that is excitatory and a surrounding area that is inhibitory or vice versa) means the positive and negative parts cancel each other out.
So cells do not maintain their activity if nothing is changing as brain isn’t interested so fewer action potentials needed - saves energy.
Briefly describe the knee jerk response.
Inhibitory connection.
Stretch in muscle fed into the spinal cord and activates the alpha motoneurons going out to the same nerve but inhibits the nerves that invade the opposite muscle.
Describe the time course of inhibition studied by Eccles et al.
Used the knee jerk response as a basis.
Changed the relative timing between the two inputs to understand their interaction with each other.
Trying to map out the time course of the inhibitory effect.
Observed that at some intervals an AP occurred and at others there wasn’t.
What conclusions did Eccles et al come to?
Inhibitory effect has 2 components.
1. action of the synapses to push the membrane potential down (hyperpolarisation) makes it a farther distance from AP threshold.
2. the time when the actual receptors are open, representing the cells being leaky (charge being poured in at a rapid rate but the charge can leak out due to channels being open) constituting an inhibitory effect.
total inhibitory effect is the sum of both of these factors.
Give 4 examples of ionotropic receptors.
- AMPA and NMDA receptors
- Nicotinic Ach receptors.
- GABAa and GABAc receptors
- Glycine receptors
Give 3 examples of metabotropic receptors.
- Metabotropic glutamate receptors.
- Muscarinic Ach receptors.
- GABAb receptors.
Describe GABA and glycine receptors.
Ionotropic
Mediates fast inhibition
Pentameric structure that has 4 transmembrane loops with the second forming the inner loop where Cl- ions pass.
Rho 1-3 subunits specific for GABAc receptors.
Glycine has 2 subunit classes alpha 1-4 and beta.
GABAa is pentameric with 3 alpha and 2 beta.
Name the 3 ways there can be pre or post synaptic inhibition.
- inhibitors reduces the amount of excitatory transmitter released from the nerve terminal (presynaptic only).
- reaction of the post-synaptic receptors to a constant amount of transmitter is reduced (eg. by competition).
- post-synaptic membrane may be altered in such a way that the depolarising action of the excitatory transmitter is opposed (Eccles).
What is the main inhibitory receptor found on the pre-synaptic terminals?
GABAb - when they bind GABA they affect the ability of calcium to enter the cell where there is an AP stopping the release of glutamate.
What drug mediates the modulation of synaptic receptors?
Benzodiazepines - mediates sedation and binds at the interface of the alpha/gamma 2 subunits.
What drugs modulate extra synaptic receptors?
Barbiturates - increase the affinity of GABA.
Neurosteroids - positive and negative allosteric modulation.
Alcohol - enhances GABA action.
What is the structure of GABAb receptors?
Dimeric structure.
Briefly describe suppression of inhibition and endocannabinoid action.
If a cell is stimulated for a long time the synaptic inputs into the cell vanish for a period.
How?
If cannabinoid receptors are blocked, this event is obliterated leading to the post synaptic cell to become active and triggers the release of endocannabinoids.
These pass BACK to the pre-synaptic site where they bind to receptors and block synaptic release.
Proof of reverse transmitters.
What does the strength of inhibition depend on?
concentration of intracellular chloride
