Steven A. Siegelbaum

Columbia University, New York, New York ~Professor of Neuroscience and Pharmacology; Howard Hughes Medical Institute Investigator. Made fundamental discoveries in the regulation of neuronal and cardiac functions by modulatory signaling cascades. Experiments elucidated key molecular mechanisms that underlie the acceleration of the heart by sympathetic neurohormone and that support long-term synaptic plasticity and thus learning and memory. Provided the first single-channel analysis of a modulatory transmitter action: the seratonin-induced closure on the Aplysia S-type K channel, mediated through camp-dependent phosphorylation. Found that the S-channel is dually regulated: closed by seratonin, but up-modulated by a neuropeptide, acting via arachidonic acid metabolites. Clarified how ion channels are directly gated by cyclic nucleotides, a critical event in sensory neurons. Instrumental in the identification of mammalian genes that encode ion channels important for neuronal and cardiac rhythms-the long-sought hyperpolarization-activated, camp-modulated hcn channels-and delineated mechanisms underlying their unusual gating. Provided insights into mechanisms of long-term plasticity in brain circuits. Identified novel cellular and molecular processes underlying long-term potentiation and long-term depression, and showed that hcn1 channels act at specific subsets of hippocampal synapses to gate both synaptic plasticity and learning and memory.~~