The brain acquires function by modifying its circuits in response to its own activity, thereby generating learning and memory. Extensive research establishes coincident pre- and postsynaptic activity as a generator of circuit-modifying signals, often through the action of the NMDA receptor, which can function as coincidence detector. Of the many forms of regulation, regulation by reward is particularly significant because it enables the individual to make behavioral choices guided by past experiences. The underlying mechanisms of reward regulation are particularly interesting because medium spiny neurons (MSNs) of the striatum, a major regulatory cell type of the reward circuitry, can exist in a hyperpolarized state, the so-called “Down-state”, in which the NMDA receptor does not function, making necessary use of NMDAR-independent pathways. I will discuss studies supporting the function of calcium permeable AMPA receptors (CPARs) as surrogates for the NMDA receptor in MSN regulation by reward, and the role of the cGMP-regulated protein kinase, cGKII, as a CPAR effector. This work will be related to the molecular mechanism of synaptic trafficking of GluA1-containing AMPARs and how this mechanism may provide novel forms of coincident activity detection. Finally, I will discuss how withdrawal of reward may place MSNs in a state particularly sensitive to new reward signals.
Edward Ziff received a bachelor’s degree in Chemistry from Columbia University and a Ph.D. from Princeton University in Biochemistry. As a postdoctoral student in Cambridge, he conducted early genome sequencing studies in the laboratory of Fred Sanger. Ed later served on the faculties of the Imperial Cancer Research Fund in London and Rockefeller University in New York studying mechanisms of oncogenesis and transcriptional regulation. He next joined the faculty of New York University School of Medicine, where he is now Professor of Biochemistry and Molecular Pharmacology and Neural Science and was an Investigator of the Howard Hughes Medical Institute. Ed researches brain function and neurological disease, in particular mechanisms of synaptic plasticity and neuronal homeostasis and regulation by reward. He has written on science topics for the lay public and also coauthored a popular book on DNA.
Sponsored by the NYU-ECNU Institute of Brain and Cognitive Science at NYU Shanghai