Hippocampal cortical interactions and the extraction of knowledge from episodic memory

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My research program focusses on the neuro-computational basis of memory and the dynamic interactions among neuronal populations that lead to the brain's ability to create an adaptive model of its. Over the past 35 years, I have made major contributions to understanding central synaptic plasticity mechanisms, spatial information processing, cortico-hippocampal interactions and memory consolidation, and significantly advanced technologies for systems neuroscience investigation. In the course of this work I have provided outstanding training to 33 graduate students, and 37 postdocs, most of whom are pursuing research careers at major universities. Over the next 5 years, my overall programme (including other support) will provide training for at least 4 undergrads, 10 graduates and 7 postdocs, as we continue to study the impact of hippocampal back projections to the neocortex on neural coding and neural plasticity in that structure. Understanding this impact is key to understanding why, in the absence of a functional hippocampus, the neocortex is unable to form new memories or to extract general knowledge from experience efficiently. It is also key to understanding a mode of computational knowledge acquisition and representation that may have far reaching impacts on information and computer technology. "What does the hippocampus (HC) do for neocortex (NC)?" This question is addressed under three specific subtopics: 1) How does HC affect the actual coding properties of NC neurons? In particular, is the apparent spatial modulation of object encoding and behavior in some NC regions inherited from "place coding" in HC? Do NC coding statistics change as the brain refines its model of the world, and does HC enable such changes? 2) To what degree does the reactivation of memory traces observed in NC during rest and slow-wave-sleep depend on HC output? Is the dependence different for new memories compared to reinstated or spontaneously retrieved old memories? For new memories, is HC required for NC reactivation per se, or rather is it merely required for synchronizing cortical reactivation over broad areas? Which parts of NC are most strongly activated by HC outflow during memory reactivation? Does the relative timing between NC and HC memory reactivation change as memories gradually become consolidated (i.e., does HC initially lead HC and subsequently follow it)? 3) Is HC necessary for learning-associated dendritic spine plasticity in NC? Does HC contribute to the regulation of expression of NC neurotrophins which are crucial to neuroplasticity in NC? These questions are addressed using various combinations of multi-neuron recording, using electrophysiological and optical imaging methods, neocortical voltage recording, structural and functional imaging of NC dendritic spines in vivo, and immunochemical quantification of neurotrophic factors, in animals with intact or inactivated HC function.