A gap exists between cellular-molecular mechanisms of synaptic plasticity as studied in in vitro preparations and the implications of these findings for the operations of real networks in the behaving animal. One reason is that experimental access to the emergent properties of cooperating neurons has been impossible until quite recently, although it has long been recognized that cooperation of complex neuronal systems is a prerequisite for neuronal plasticity. Physiological patterns in the intact animal provide a logical starting point o examine whether such patterns satisfy the requirements of potentiation. In a formal model we hypothsized that synaptic modification in the hippocampus requires two stages; the information gathering (theta) phase and subsequent consolidation phase associated with highly synchronous cooperative bursts of CA3 and CA1 pyramidal cells (sharp waves, SPW). The latter mechanism also allows slow transfer of the memory trace to retrohippocampal/neocortical structures. The goal of the present project is to examine the modifiability of network cooperativity of pyramidal cells during SPW in the hippocampal formation as a result of experience and provide evidence that SPW-associated population bursts can induce synaptic modification in the intact brain. Multisite neuronal recordings with silicon microprobes in awake rats and intracellular recording and anesthetized animals will be used to address these issues. Specifically, we propose (a) to test whether SPW bursts associated with electrical stimulation of afferent paths or sensory stimuli in can induce potentiation of the evoked responses, (b) to examine whether activation of pyramidal neurons by exploration of paradoxical phase of sleep can modify the sequential structural of SPW-associated population events during subsequent slow wave sleep episodes. Overall, these experiments will reveal the mechanisms and intrinsic rules of population bursting in the hippocampus and elucidate whether such cooperative patterns can serve to preserve representations obtained during attentive, information gathering theta) states. Most importantly, they will address the issue whether long-term potentiation, a physiological model of memory, occurs endogenously in the behaving animal.
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