I would like to pharmacologically increase presynaptic neurotransmitter release in mice CNS in vivo (through the extracellular micro-infusion of a compound). Which strategy would you recommand?
How to increase presynaptic neurotransmitter release artificially :-
potassium dominates the resting potential and sodium controls the nerve impulse, it is calcium that regulates the release of a neurotransmitter into the synaptic cleft. However, researchers have just begun to understand the process by which an arriving action potential triggers the release of neurotransmitter and the role that calcium plays in that process.
Since the action potential is a complex phenomenon, involving the opening and closing of both sodium and potassium channels as well as changes of the membrane potential, more than one aspect of the action potential might control neurotransmitter release. An elegant approach to this problem was provided by Bernard Katz and Miledi (1967), who utilized two ion-specific neurotoxins- tetrodotoxin (TTX) and tetrathylammonium (TEA)- to rule out the effects of ionic movements in governing neurotransmitter release. TTX selectively blocks the voltage-regulated sodium channels of the axon. When it is applied to the presynaptic terminal, the action potential is not propagated, and, for that reason, no neurotransmitter is released by the endfoot. But if the endfoot is electrically depolarized, the chemical synapse continues to function in its normal fashion. This means that the operation of sodium channels is not necessary for neurotransmitter release.