Anteromedial Thalamus Gates the Selection & Stabilization of Long-Term Memories.

Memories initially formed in hippocampus gradually stabilize to cortex, over weeks-to-months, for long-term storage. The mechanistic details of this brain re-organization process remain poorly understood. In this study, we developed a virtual-reality based behavioral task and observed neural activity patterns associated with memory reorganization and stabilization over weeks-long timescales. Initial photometry recordings in circuits that link hippocampus and cortex revealed a unique and prominent neural correlate of memory in anterior thalamus that emerged in training and persisted for several weeks. Inhibition of the anteromedial thalamus-to-anterior cingulate cortex projections during training resulted in substantial memory consolidation deficits, and gain amplification more strikingly, was sufficient to enhance consolidation of otherwise unconsolidated memories. To provide mechanistic insights, we developed a new behavioral task where mice form two memories, of which only the more salient memory is consolidated, and also a technology for simultaneous and longitudinal cellular resolution imaging of hippocampus, thalamus, and cortex throughout the consolidation window. We found that whereas hippocampus equally encodes multiple memories, the anteromedial thalamus forms preferential tuning to salient memories, and establishes inter-regional correlations with cortex, that are critical for synchronizing and stabilizing cortical representations at remote time. Indeed, inhibition of this thalamo-cortical circuit while imaging in cortex reveals loss of contextual tuning and ensemble synchrony in anterior cingulate, together with behavioral deficits in remote memory retrieval. We thus identify a thalamo-cortical circuit that gates memory consolidation and propose a mechanism suitable for the selection and stabilization of hippocampal memories into longer term cortical storage.