A distinct subcircuit in medial entorhinal cortex mediates learning of interval timing behavior during immobility

Over 60 years of research has established that medial temporal lobe structures, including the hippocampus and entorhinal cortex, are necessary for the formation of episodic memories (i.e. memories of specific personal events that occur in spatial and temporal context). While prior work to establish the neural mechanisms underlying episodic memory has largely focused on questions related spatial context, recently we have begun to investigate how these brain structures could be involved in encoding aspects of temporal context. In particular, we have focused on how medial entorhinal cortex, a structure well known for its role in spatial memory, may also be involved in encoding interval time. To answer this question we have developed an instrumental paradigm for head-fixed mice that requires both immobile interval timing and locomotion-dependent navigation behavior. By combining this behavioral paradigm with large-scale cellular resolution functional imaging and optogenetic-mediated inactivation, our results suggest that MEC is required for learning of interval timing behavior and that interval timing could be mediated through regular, sequential neural activity of a distinct subpopulation of neurons in MEC that encode elapsed time during periods of immobility (Heys and Dombeck, 2018; Heys et al, 2020; Issa et al., 2020). In this talk, I will discuss these findings and discuss our on-going work to investigate the principles underlying the role of medial temporal lobe structures in timing behavior and episodic memory.