David Sulzer

David Sulzer (born November 6, 1956) is an American neuroscientist and musician.

He is a professor at Columbia University Medical Center in the departments of psychiatry, neurology, and pharmacology.

Sulzer's laboratory investigates the interaction between the synapses of the cerebral cortex and the basal ganglia, including the dopamine system, in habit formation, planning, decision making, and diseases of the system.

His lab has developed the first means to optically measure neurotransmission, and has introduced new hypotheses of neurodegeneration in Parkinson's disease, and changes in synapses that produce autism and habit learning.

Under the stage name Dave Soldier, he is known as a composer and musician in a variety of genres including avant-garde, classical, and jazz.

Sulzer works on basal ganglia and dopamine neurons, brain cells of central importance in translating will to action.

His team have introduced new methods to study synapses, including the first means to measure the fundamental "quantal" unit of neurotransmitter release from central synapses.

They reported the first direct recordings of quantal neurotransmitter release from brain synapses using an electrochemistry technique known as amperometry, based on the method of Mark Wightman, a chemist at the University of North Carolina, to measure release of adrenaline from adrenal chromaffin cells.

They showed that the quantal event at dopamine synapses consisted of the release of about 3,000 dopamine molecules in about 100 nanoseconds.

They further showed that the quantal events could "flicker" due to extremely 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 accumulated like genuine neurotransmitters into neurons and synaptic vesicles.

This is used to observe neurotransmitter release and reuptake from individual synapses in video.

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.

By introducing the "weak base hypothesis" of amphetamine action, for measuring amphetamine's effects on the quantal size of dopamine release, intracellular patch electrochemistry to measure dopamine levels in the cytosol, and providing real-time measurement of dopamine release by reverse transport, Sulzer's lab showed how amphetamine and methamphetamine release dopamine and other neurotransmitters and exert their synaptic and clinical effects.

They showed how methamphetamine neurotoxicity occurs due to dopamine-derived oxidative stress in the cytosol followed by induction of autophagy, and with Nigel Bamford of the University of Washington, how these drugs activate long-term changes in the cortical synapses that project to the striatum.

They call these "chronic postsynaptic depression" and "paradoxical presynaptic potentiation", which may explain drug dependence and addiction.

Sulzer explains in an interview on NOVA that his interest in understanding mechanisms of addiction stem from crashing a talk by William Burroughs at Naropa Institute in 1980, where Burroughs claimed that new synthetic opiates would be so powerful that users would become addicts with a single dose.

In an interview in Nature Medicine on his lab's discovery of the mechanism by which nicotine filters synaptic noise and can focus attention to tasks, he recalls his father's early death due to smoking, saying "if some idiot or drug company is going to twist things around, the only thing that would come out of [this research] that I'd be horrified by is if people used it to advocate smoking. I think it would be a real travesty if that happened."

Sulzer and his lab also studied nerve impulses in Parkinson's and Huntington's diseases, schizophrenia, drug addiction, and autism.

They helped to establish the role of autophagy by lysosomes in neuronal disease.

They showed the role of neuromelanin, the pigment of the substantia nigra, in methamphetamine neurotoxicity, and Huntington's disease.

With Ana Maria Cuervo of Albert Einstein College of Medicine they showed that a cause of Parkinson's disease could be due to an interference with a chaperone-mediated autophagy caused by the protein alpha-synuclein.

His work indicates that a lack of normal pruning of synapses could underlie the development of autism, and that in turn may also my due to inhibited neuronal autophagy in patients, due to overactivation of the mTOR pathway during childhood and adolescence.

He received a Ph.D. in biology from Columbia University in 1988.

He founded the Gordon Conference on Parkinson's Disease, the Dopamine Society (with Louis-Eric Trudeau) and the journal Nature Parkinson's Disease (with Ray Chaudhuri).

1996 - James T. Shannon Award, National Institute on Drug Abuse, National Institutes of Health, USA

Sulzer wrote a book on scientific principles that underlie music and sound "Music Math and Mind" [Columbia University Press], 2021), and teaches a related course at Columbia University on the physics and neuroscience of music and sound.

2008 - McKnight Award in Neuroscience for Technical Innovation

2012 - Keynote Lecture in Cellular Neuroscience, Yale University, New Haven, Connecticut, USA

He co-ran the original science cafe, "Entertaining Science" from 2012 to 2019, with its founder (2002), chemist and writer Roald Hoffmann in Greenwich Village at the Cornelia Street Cafe.

2013 - Helmsley Award for Scientific Research

In 2017, his lab introduced the role of autoimmune response in Parkinson's disease patients, which answers a century-old mystery on the role of immune system activation in that disorder.

The Sulzer lab has published over 250 papers on this research.

For his work, Sulzer has received awards from the McKnight Foundation, the National Institute on Drug Abuse (NIDA), and NARSAD.

He ran the Basic Neuroscience NIH / NIDA (T32) training program for postdoctoral research in basic neuroscience at Columbia.

2017 - Presidential Lecture, Society of Neuroimmune Pharmacology

2019 - Distinguished Lecture in Medicinal Chemistry, University of Minnesota, USA

2020 - Youdim / Finberg Award, Hebrew University, Jerusalem, Israel

2020 - Raymond D. Adams Lecture, Harvard University, Mass General Hospital, Boston, Massachusetts, USA