This is an application for a K05, Senior Scientist Award. Throughout his career, the candidate has pursued the neurobiological and computational basis of memory. In the late 1970's, he provided the first evidence for the biological realization of Hebb's neurophysiological postulate for associative memory, by showing that synaptic long-term potentiation (LTP) in the hippocampus involved the cooperation of converging inputs. Since then, he has made numerous contributions to understanding the process of LTP at both the biophysical and behavioral levels, and contributed significantly to the development of neural network theories of both memory and the neural encoding of spatial information (cognitive maps). Motivated by the idea that memories are properties of neural populations, supported by enhanced mutual connections, the candidate has guided the development of methods that currently routinely enable recording simultaneously from over 100 neurons in the freely behaving rodent. This method has opened an unprecedented window on neuron interactions and has provided strong indirect evidence for the existence of Hebb's """"""""cell assemblies"""""""" and """"""""phase sequences"""""""" during a process of off-line reprocessing of recent memories in the hippocampus and neocortex. The candidate is currently Director of the Division of Neural Systems, Memory, and Aging, at the University of Arizona, a 9,000 sq. ft. research facility dedicated to memory research. The facility includes dedicated surgical, neuroanatomical and electronics engineering suites, and several specially designed controlled environments for behavioral neurophysiology. The candidate's own research team includes 5 postdoctoral, 6 graduate, and 4 undergraduate research associates, and 5 electronics, computer, and neurophysiological research specialists. The candidate's immediate and long term research goal is to understand the brain dynamics underlying the transformation of episodic memory into categorical knowledge, a process known as memory consolidation. The specific career development plan to be supported by this award is to begin to develop the technology to enable recording from up to 400 cells from the cortex and hippocampus in the behaving primate and to develop new analytical tools for understanding the behavior of cell assemblies in terms of these large populations of recorded units. The specific research projects deal with the questions of the reactivation of memory traces during sleep, how this is orchestrated by the hippocampus, and whether the process itself is truly of behavioral significance.
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