David Sulzer - Studies On Synapses

Studies On Synapses

The Sulzer laboratory has made contributions to understanding the basal ganglia and dopamine neurons, brain cells of central importance in translating will to action. They have introduced new methods to demonstrate how the synapses work, including the first means to measure the fundamental "quantal" unit of neurotransmitter release from central synapses and the first video means to observe release of neurotransmitter from individual synapses.

The fundamental unit of chemical neurotransmission is due to the "quantal release event", which is due to the fusion of synaptic vesicles with the plasma membrane, which provides for release of the encapsulated neurotransmitter from the synapse. Sulzer and colleagues reported the first direct recordings of quantal neurotransmitter release from brain synapses using an electrochemistry technique known as amperometry using microelectrodes in an approach previously used by Mark Wightman, a chemist at the University of North Carolina, to measure release of adrenaline from adrenal chromaffin cells.

Their experiments showed that the quantal event at dopamine synapses consisted of the release of about 3,000 dopamine molecules in about 100 nanoseconds. Further studies followed that showed that the quantal events could "flicker" due to extremely rapid rapid opening and closing of the a synaptic vesicle fusion pore (at rates as high as 4,000 times a second) with the plasma membrane. This approach also demonstrated that the "size" of the quanta could be altered in numerous ways, for example by the drug L-DOPA, a drug so used to treat Parkinson's Disease.

Sulzer's lab, together with that of Dalibor Sames, a chemist at Columbia University, introduced "fluorescent false neurotransmitters", compounds that are accumulated like genuine neurotransmitters into neurons and synaptic vesicles. The use of fluorescent false neurotransmitters provides the first visual approach to observe neurotransmitter release and reuptake from individual synapses in video. These approaches are enabling important insights into the means by which particular synapses are selected or filtered to allow the brain to change and create new learning and memories.

Sulzer, along with his mentor Stephen Rayport, showed that the neurotransmitter glutamate is released from dopamine neurons, an important exception to the Dale's principle that a neuron releases the same transmitter from each of its synapses.