Distinct CA1 inputs support shifts in neural dimensionality and memory resolution

Abstract

Event-based memories may be encoded with high (e.g., episodic) or low (e.g., gist) mnemonic resolution. While the CA1 region of the hippocampus encodes events at both scales, it is unclear how such dual coding emerges. Consistent with theoretical predictions1,2, here we show that trisynaptic (from CA3) and monosynaptic (from the medial entorhinal cortex) projections to CA1 encode high- and low-resolution event-based memories, respectively. Recruitment of the trisynaptic pathway during contextual fear conditioning promotes feedforward inhibition of CA1 via activation of parvalbumin-positive (PV+) interneurons. This allows sparse encoding of event-based memories in high-dimensional neural states that support high-resolution contextual fear memories, where mice exhibit conditioned fear only in the training context and not similar contexts. Inhibiting this input during training reduces activation of CA1 PV+ interneurons and feedforward inhibition, shifting neural dynamics to low-dimensional states that support low-resolution contextual fear memories where mice freeze in the training context and similar contexts. These experiments identify a circuit-based mechanism that causally links the dimensionality of CA1 neural dynamics to mnemonic resolution.