A thalamo-hippocampal circuit regulating memory precision during contextual learning

The balance between memory specificity and generalization is essential for animals’ adaptive behaviours in diverse contexts, and is controlled by thalamus and hippocampus. Yet, whether and how thalamo-hippocampal circuitry regulates this balance remains elusive. Using single-neuron projectome analysis, we found that dorsal and ventral subregions of ventral CA1 (vCA1d and vCA1v) received inputs from two distinct neuronal populations in the nucleus of reuniens (NRe ^vCA1d and NRe ^vCA1v neurons), respectively. Cell type-specific trans-synaptic retrograde tracing and circuit-barcoded single-cell RNA sequencing of NRe ^vCA1d and NRe ^vCA1v neurons uncovered distinct presynaptic inputs as well as gene expression patterns underlying their different intrinsic excitabilities and spike waveforms. Using single-unit recording, circuit specific chemogenetic inhibitions, and miniscope Ca ²⁺ imaging, we found that NRe ^vCA1d (but not NRe ^vCA1v ) neurons and downstream vCA1d neurons exhibited reduced contextual discriminability, promoting memory generalization after threat learning. These results demonstrate that the NRe-vCA1d circuit regulates memory precision by promoting memory generalization over specificity.