Neurophysiological mechanisms of long term-memory : from hippocampal to olfactory networks

Orateur : Lisa ROUX (New York University Neuroscience Institute)

The formation of episodic and spatial memories requires a two-stage process that includes an "online" encoding phase, during which the memory trace is initially labile and vulnerable to interference, followed by an "offline" consolidation phase. Stabilization of the memory trace is thought to rely on reactivations of hippocampal networks, which would facilitate the progressive strengthening of the connections that represent the original experience. Reactivations are mainly coordinated by network events called sharp wave ripple oscillations (SPW-Rs) which occur during slow wave sleep, rest and consummatory behaviors. Rodent studies showed that during SPW-Rs, neurons coding for specific locations in space ("place cells") replay previous waking activity patterns, corresponding to entire spatial trajectories. The compressed temporal dynamic of these reactivations (15-20 times faster than typical running speed), combined with the strong synchronous activity in the hippocampal network associated with SPW-Rs, would be ideal conditions for synapse reinforcement to take place. Yet the role of SPW-Rs in stabilizing the hippocampal network during learning has never been tested directly. To address this question, we used the spatial information coded by place cells : we reasoned that if SPW-Rs are necessary for the network stabilization, disrupting neuronal activity during those events should result in an altered mental representation of space ("cognitive map"). Mice performed a spatial memory task requiring daily learning of three hidden reward locations on a familiar cheeseboard multi-well maze. SPW-Rs occurred regularly during reward consumption at the new goal locations. We used online position tracking, closed-loop feedback, and optogenetic stimulation to suppress pyramidal cell activity in the CA1 region contingent upon detection of awake SPW-Rs, specifically at the goal locations. Silicon probe recordings, combined with focal light delivery, allowed us to simultaneously record "SPW-R-silenced" and control place cells (non-illuminated/non-silenced and/or neurons silenced with a delay relative to SPW-R occurrence). We found that the spatial firing patterns of SPW-R-silenced place cells were modified after learning, to a larger extent than those of control place cells. Moreover, while control place cells showed increased spatial information content after learning, SPW-R-silenced place cells did not. These observations indicate that SPW-R-associated neuronal activity is necessary to "refine" and stabilize hippocampal place fields. Awake SPW-Rs could thus play an active role in the maintenance of the cognitive map upon learning.

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