Dylan C. Barnes, Ph.D. - US grants

DESCRIPTION (provided by applicant): Sleep structure (REM/Slow wave activity [SWS]) can be modified after learning, and in some cortical circuits, sleep is associated with replay of the learned experience. While the majority of this work has focused on neocortical and hippocampal circuits, the olfactory system may offer unique advantages as a model system for exploring sleep and memory, given the short, non-thalamic pathway from nose to primary olfactory (piriform cortex), and rapid cortex-dependent odor learning. The rat piriform cortex is hypo-responsive to odors during SWS which accounts for nearly 40% of each 24 hour period. The duration of slow-wave activity in the piriform cortex is enhanced immediately post-conditioning, and this increase is significantly correlated with subsequent memory performance. Together, these results suggest the piriform cortex may go offline during SWS to facilitate consolidation of learned odors with reduced external interference. The goal of this project is to illuminate the specific role of SWS in odor memory consolidation by modifying post-training SWS bouts by introducing possibly interfering patterns through electrical and pharmacological stimulation. Post-training SWS may contribute to memory consolidation by allowing replay during a time of reduced sensory input, and thus reduced possibility of interference. In the first aim of this projet we take advantage of the fact that the piriform cortex is hypo-responsive to odors during SWS, yet odors are still weakly effective. The function of the piriform cortex in odor memory is to both learn spatiotemporal patterns of olfactory bulb output (odor objects) and tie those patterns to hedonic meaning and context through links with other brain regions. By using precise spatiotemporal patterns of electrical olfactory bulb stimulation as the CS+ and CS- during differential odor-fear training, and then applying those stimuli, or different stimuli during speciic behavioral states post-training, we can directly test the interference and replay hypothesis of slow-wave sleep and memory consolidation. ACh plays a critical role in olfactory system function, odor memory and perception. The primary source of ACh to the olfactory system is the HLDB, which can be electrically stimulated, elevating ACh throughout the olfactory system. During SWS, ACh levels drop, placing cortical cholinergic dependent plasticity in a unique state, potentially important for SWS-dependent memory consolidation. The second aim of this project will begin to test the role of ACH in SWS memory effects by artificially elevating ACH during SWS through HLDB electrical stimulation.