: The role of hippocampus in memory is well established and the importance of subcortical structures connected to the hippocampus has been known since the pioneering work of Korsakoff and Wernicke. Although certain memory deficits are best described in the frameworks of a diencephalo-hippocanipal syndrome, virtually nothing is known about how these forebrain systems interact with each other and how their interaction is organized by the brainstem so as to account for the robust state dependent changes underlying learning and memory. The central focus of this project is the subcortical regulation of hippocampal function and is guided by the general hypothesis that the role of this regulation is not only to switch the hippocampal EEG between theta and non-theta patterns but also to build dynamic associations between several limbic structures that are synchronized by the theta rhythm. Extrahippocampal theta activity has been recently described in a number of structures under urethane anesthesia but never under natural conditions. The proposed research will test the hypotheses that (1) brainstem/diencephalic systems, in addition to switching between theta and non-theta take part in behaviorally-related fine tuning of hippocampal activity during natural theta states; (2) theta rhythmic activity plays a role in neuronal cooperation between different limbic structures and brainstem structures exhibiting theta rhythmic activity specifically regulate this traffic; (3) theta rhythmic activity generated in the septum and the mammillaiy complex exerts feedback regulatory influence on brainstem nuclei involved in brain state regulation. Phasic and rhythmic synchronization of neuronal activity is critical to the concerted action of spatially separated structures in the brain. Theta synchrony provides an excellent model to study such cooperation and the way in which it differs in specific behavioral states. Our experiments will take advantage of waking exploration and sleep as a natural experiment trying to inform us about the components of the memory building process. The timeliness of this work is underlined by the recent upsurge of interest and data linking sleep, hippocampal activity and successive phases of information processing in non-REM and REM sleep.
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