David Sulzer, PhD
Dr. Sulzer's lab investigates the function and alteration of the synapses of the cortex and the basal ganglia including the dopamine system in normal behaviors such as habit formation and action selection, and in diseases of the system. Their work has made fundamental contributions to understanding the roles of these synapses in Parkinson's and Huntington's diseases, schizophrenia, autism, and drug addiction. His laboratory developed new optical, electrophysiological and electrochemical methods including the first direct recordings of quantal neurotransmitter release from synapses, the fundamental unit of neurotransmission, and the first optical methods to observe neurotransmitter release and reuptake. His work increased the understanding of the life cycle of synaptic vesicles, cellular structures that package neurotransmitter release.
Among the discoveries and inventions of the laboratory are 1) discovery of co-release of glutamate from dopamine neurons (with Stephen Rayport) 2) introduction of the weak base mechanism of amphetamine action and the first direct measurement of reverse transport, an important property of amphetamine 3) the first recording of quantal neurotransmitter release from CNS synapses, by using amperometry at dopamine terminals 4) discovery of multiple means to alter quantal size, including the effects of L-DOPA, amphetamine, vesicle transporter expression (with Robert Edwards), rebound hyperacidification, and discovery of fusion pore flickering 5) discovery of the biosynthetic pathway of neuromelanin 6) introduction of & the role of autophagic degradation in synaptic development, which may underlie forms of autism, 7) discovery of how alpha-synuclein and other proteins are degraded by chaperone-mediated autophagy, which may underlie forms of Parkinson’s (with Ana Maria Cuervo) 8) the first optical analysis of corticostriatal transmission, showing the role of activity, dopamine, and acetylcholine in synaptic selection (with Nigel Bamford) 9) co-invention of fluorescent false neurotransmitters, the first optical means to observe neurotransmitter release and reuptake from CNS terminals (with Dalibor Sames) 10) discovered the role of glutamate in controlling axonal outgrowth and branching 11) discovery of antigen presentation by neurons targeted in Parkinson’s disease, which may underlie targeted cell death.
The Sulzer lab has published over 140 papers on this research and has received awards from the McKnight, Helmsely, Picower, Michael J Fox, Simons, HDSA Foundations, NIH, and NARSAD.