Lateral entorhinal cortex suppresses drift in cortical memory representations

Abstract

Memory retrieval is thought to depend on the reinstatement of cortical memory representations guided by pattern completion processes in the hippocampus. The lateral entorhinal cortex (LEC) is one of the intermediary regions supporting hippocampal-cortical interactions and houses neurons that prospectively signal past events in a familiar environment. To investigate the functional relevance of the LEC’s activity for cortical reinstatement, we pharmacologically inhibited the LEC and examined its impact on the stability of ensemble firing patterns in one of the LEC’s efferent targets, the medial prefrontal cortex (mPFC). When male rats underwent multiple epochs of identical stimulus sequences in the same environment, the mPFC maintained a stable ensemble firing pattern across repetitions, particularly when the sequence included pairings of neutral and aversive stimuli. With LEC inhibition, the mPFC still formed an ensemble pattern that accurately captured stimuli and their associations within each epoch. However, LEC inhibition markedly disrupted its consistency across the epochs by decreasing the proportion of mPFC neurons that stably maintained firing selectivity for stimulus associations. Thus, the LEC stabilizes cortical representations of learned stimulus associations, thereby facilitating the recovery of the original memory trace without generating a new, redundant trace for familiar experiences. Failure of this process might underlie retrieval deficits in conditions associated with degeneration of the LEC, such as normal aging and Alzheimer’s disease.SIGNIFICANCE STATEMENTTo recall past events, the brain needs to reactivate the activity patterns that occurred during those events. However, such reinstatement of memory traces is not trivial because it goes against the brain’s natural tendency to restructure the activity patterns continuously. We found that dysfunction of a brain region called the lateral entorhinal cortex (LEC) worsened the drift of the brain activity when rats repeatedly underwent the same events in the same room and made them behave as if they had never experienced these events before. Thus, the LEC stabilizes the brain activity to facilitate the recovery of the original memory trace. Failure of this process might underlie memory problems in elderly and Alzheimer’s disease patients with the degenerated LEC.

Brain-wide screen of prelimbic cortex inputs reveals a functional shift during early fear memory consolidation

“…Out of the regions projecting to PL engrams, we selected six brain areas with consistent input tracing for further investigation, because of their previously documented implication in various aspects of fear memory: The EC, for its role in memory formation (Roy et al, 2017) and its known projection to the mPFC necessary at encoding (Kitamura et al, 2017) and retrieval (Pilkiw et al, 2022); the RSP for its necessity for recent (Cowansage et al, 2014) and remote fear memory recall (Todd et al, 2016); the INS for its requirement during the consolidation and expression of contextual fear memories (Alves et al, 2013), as well as for its regulation of fear expression (Gehrlach et al, 2019; Klein et al, 2021); vCA1 for its importance for CFC encoding (Kim & Cho, 2020) and recent recall (Jimenez et al, 2020); the BLA for the role of BLA to PL projections in memory encoding (Kitamura et al, 2017; Klavir et al, 2017) and PL to BLA projections in memory recall (Do-Monte et al, 2015; Kitamura et al, 2017); and the CLA as CLA to EC projections are necessary during memory encoding (Kitanishi & Matsuo, 2017) and for its involvement in attention (Atlan et al, 2018).…”