Medial entorhinal cortex mediates learning of context-dependent interval timing behavior.

Episodic memory requires encoding the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC 'time cells', which fire at specific moments during interval timing tasks, collectively tiling the entire timing period. It has been hypothesized that MEC time cells could provide temporal information necessary for episodic memories, yet it remains unknown whether they display learning dynamics required for encoding different temporal contexts.

Medial entorhinal cortex plays a specialized role in learning of flexible, context-dependent interval timing behavior.

Episodic memory requires encoding the temporal structure of experience and relies on brain circuits in the medial temporal lobe, including the medial entorhinal cortex (MEC). Recent studies have identified MEC 'time cells', which fire at specific moments during interval timing tasks, collectively tiling the entire timing period. It has been hypothesized that MEC time cells could provide temporal information necessary for episodic memories, yet it remains unknown whether MEC time cells display learning dynamics required for encoding different temporal contexts.

Direct cortical inputs to hippocampal area CA1 transmit complementary signals for goal-directed navigation.

The subregions of the entorhinal cortex (EC) are conventionally thought to compute dichotomous representations for spatial processing, with the medial EC (MEC) providing a global spatial map and the lateral EC (LEC) encoding specific sensory details of experience. Yet, little is known about the specific types of information EC transmits downstream to the hippocampus. Here, we exploit in vivo sub-cellular imaging to record from EC axons in CA1 while mice perform navigational tasks in virtual reality (VR).

Signatures of rapid plasticity in hippocampal CA1 representations during novel experiences.

Neurons in the hippocampus exhibit a striking selectivity for specific combinations of sensory features, forming representations that are thought to subserve episodic memory. Even during completely novel experiences, hippocampal "place cells" are rapidly configured such that the population sparsely encodes visited locations, stabilizing within minutes of the first exposure to a new environment. What mechanisms enable this fast encoding of experience? Using virtual reality and neural population recordings in mice, we dissected the effects of novelty and experience on the dynamics of place field formation.

Parallel processing of sensory cue and spatial information in the dentate gyrus.

During exploration, animals form an internal map of an environment by combining information about landmarks and the animal's movement, a process that depends on the hippocampus. The dentate gyrus (DG) is the first stage of the hippocampal circuit where self-motion ("where") and sensory cue information ("what") are integrated, but it remains unknown how DG neurons encode this information during cognitive map formation. Using two-photon calcium imaging in mice running on a treadmill along with online cue manipulation, we identify robust sensory cue responses in DG granule cells.

Alternating sources of perisomatic inhibition during behavior.

Interneurons expressing cholecystokinin (CCK) and parvalbumin (PV) constitute two key GABAergic controllers of hippocampal pyramidal cell output. Although the temporally precise and millisecond-scale inhibitory regulation of neuronal ensembles delivered by PV interneurons is well established, the in vivo recruitment patterns of CCK-expressing basket cell (BC) populations has remained unknown. We show in the CA1 of the mouse hippocampus that the activity of CCK BCs inversely scales with both PV and pyramidal cell activity at the behaviorally relevant timescales of seconds.

Impaired hippocampal place cell dynamics in a mouse model of the 22q11.2 deletion.

Hippocampal place cells represent the cellular substrate of episodic memory. Place cell ensembles reorganize to support learning but must also maintain stable representations to facilitate memory recall. Despite extensive research, the learning-related role of place cell dynamics in health and disease remains elusive.