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

Abstract

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.

The thalamic reuniens is associated with consolidation of non-spatial memory too

“…The NRe may, however, be one among a number of thalamic sites involved in remote recall. There is recent evidence that disengagement of the anterodorsal thalamic nuclei facilitates remote contextual fear memory recall (Vetere et al, 2021), whereas activation of the anteromedial thalamic nuclei is relevant for remote memory for differentially-reinforced contexts (Toader et al, 2023). Together, this evidence suggests that several midline thalamic nuclei support consolidation and / or remote memory recall.…”

Closed-loop modulation of remote hippocampal representations with neurofeedback

“…Current animal models of memory are not designed to allow the direct study of the neural substrates of retrieval not confounded by sensory cues or the decision to act. First, current experimental approaches typically engage retrieval by presenting external cues such as those found in a particular spatial context 1,[18][19][20] . These cues can strongly influence patterns of brain activity, including spiking in brain regions like the hippocampus 6 that contribute to memory formation and retrieval 19 .…”

Neural activity ramps in frontal cortex signal extended motivation during learning

“…For all analysis, this dF/F was then normalized by z-scoring the entire time series across a session. To identify statistically significant transients, we first calculated an estimate of the noise for each cell using a custom MATLAB script, with a previously described method 56,57 . In essence, we identified the limiting noise cutoff level for a given cell using time periods that are unlikely to contain neural events, and then defined a transient as significant if it reached above at least 3σ of this estimated noise level.…”