Abstract

Synapses are the electrical switches of the brain, underpinning much of the signaling between neurons and directly involved in nearly all aspects of innate and learned behaviors. The key signaling machinery – neurotransmitter receptors and transporters – are also implicated in a large number of neurological diseases or disorders and are the targets of multiple therapeutic agents and illicit substances. Synapses are sites of three choreographed processes – calcium-dependent release of neurotransmitter into extracellular spaces, detection of neurotransmitter by ion channels, and removal of neurotransmitter by transporters. In my talk I will focus on the last two activities.

On the one hand, binding of the released neurotransmitters to transmitter-gated ion channels initiates local changes in membrane potential and these changes, when summed, initiate action potentials that are propagated throughout neuronal circuits. On the other hand, the ion channels also allow for calcium entry into cells, thus initiating chemical signaling via calcium-dependent pathways. Quenching of the neurotransmitter within the synapse and surrounding spaces is accomplished by membrane-bound transporters, molecular machines that harness pre-existing ion gradients to ‘pump’ transmitter into cells, thereby enabling subsequent cycles of neurotransmitter signaling.

Here, I illuminate how neurotransmitters transduce binding events into the opening of ion channel-coupled receptors, and on the fascinating mechanisms by which neurotransmitter transporters take-up transmitter from the synaptic cleft and are modulated by clinically relevant drugs.