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Bigus, E. R.

Publications and source records attributed to Bigus, E. R..

2 recordsLinked to original sources

Hippocampal time cell dynamics evolve with learning to reflect cognitive demands

The hippocampus creates cognitive maps, or internal representations that reflect knowledge of the external world. Hippocampal time cells are thought to represent the temporal structure of experiences, or temporal context. However, it remains unknown whether hippocampal time cells display learning dynamics that reflect increased knowledge of the temporal relationships that define a context. To address this gap, we utilized a behavioral paradigm with a shaping curriculum that allows animals to systematically acquire knowledge of temporal structure, ultimately enabling them to perform a temporal Delayed Non-Match to Sample (tDNMS) task. We conducted two-photon calcium imaging on large populations of CA1 neurons as mice progressed through the curriculum--from their initial exposure to the task structure to their successful discrimination of context at the end of training. Time cells were present from the outset, yet their activity evolved with experience, both at the single-cell level and across the population. Notably, at key moments in the curriculum, time cell dynamics adapted to reflect whether mice generalized across contexts or discriminated between them. Our findings suggest that CA1 time cells not only represent temporal context but may also reflect the processes by which temporal relationships are utilized. Hippocampal time cells therefore serve as a cognitive map, representing temporal relationships in a manner that reflects cognitive demands.

neuroscience↗

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. To explore this, we developed a novel behavioral paradigm that requires distinguishing temporal contexts. Combined with methods for cellular resolution calcium imaging, we find that MEC time cells display context-dependent neural activity that emerges with task learning. Through chemogenetic inactivation we find that MEC activity is necessary for learning of context-dependent interval timing behavior. Finally, we find evidence of a common circuit mechanism that could drive sequential activity of both time cells and spatially selective neurons in MEC. Our work suggests that the clock-like firing of MEC time cells can be modulated by learning, allowing the tracking of various temporal structures that emerge through experience.

neuroscience↗