Dynamics of Hippocampo-Cortical Networks in Learning and Memory – DyNet

The ‘two-stage’ theory of memory posits that memory traces initially formed in the hippocampus during the waking state are progressively transferred to the neocortex during sleep, where they are stored and available for long term recall. Candidate target neocortical areas include the medial prefrontal cortex (mPFC), which receives monosynaptic input from the hippocampus. Coordination between the two structures could involve several brain oscillations such as hippocampal theta (8 Hz) and ripples (200 Hz), cortical delta waves (0.1–4 Hz), and thalamo-cortical spindles (10–20 Hz). Accordingly, hippocampal and prefrontal theta oscillations coordinate during learning, leading to the emergence of specific cell assemblies, and task-related neural activity patterns are subsequently replayed during sleep, both in the hippocampus and mPFC. We were the first to demonstrate the long hypothesized causal role in memory consolidation for hippocampal ripples and associated replay, and for their coordination with delta waves and spindles. During wake, memory traces are reactivated to guide ongoing behavior. Hippocampal and mPFC networks are also involved in this process. For instance, the firing patterns of hippocampal cells predicts future choices of the animal in spatial tasks, and this modulation critically depends on mPFC inputs through thalamic relays.

The aims of the current project are to propose for the first time an analysis of the formation, consolidation and recall of memory traces both at the mesoscopic scale (oscillations) and across local neural networks (spatio-temporal firing patterns among large cell ensembles), simultaneously in hippocampus and mPFC, and to provide causal evidence for the role of relevant spiking patterns in shaping circuits and behaviors, using innovative technologies that allow for unprecedented spatio-temporal precision. We will combine state-of-the art miniature optical and electrophysiological systems, together with optogenetic tools, to investigate neural coding of memory trace formation and recall across the hippocampus and mPFC. We will thus simultaneously record local field potentials and hundreds of single neurons across days, and dynamically alter activity of these neurons while the freely moving animals are engaged in spatial memory tasks and during sleep. By altering or mimicking endogenous patterns, we will be able to directly test their causal roles in memory.