Conjunctive Coding of Space and Non-Spatial Variables in the Medial Entorhinal Cortex during Navigation and Evidence Accumulation

Abstract

The medial entorhinal cortex (mEC) and hippocampus (HPC) are both critically involved in the formation and maintenance of cognitive maps. Although historically studied during spatial navigation, such mental maps may be an instance of a common mechanism for organizing knowledge across many domains. For example, the hippocampal formation encodes not only locations in navigational space but also 'locations' in other continuous task-relevant variables, such as visual space, sound frequency, and sensory evidence, among others. Yet, whether or how cognitive maps conjointly represent dimensions across different domains is less well understood. A recent study demonstrated integration of spatial location and sensory evidence in the HPC, but whether there is similar joint encoding across these dimensions in mEC, a major input to HPC, is unknown. Understanding whether such conjunctive coding exists in the mEC is essential for uncovering how cognitive maps are constructed and utilized to guide complex behaviors. To close this knowledge gap, we use an established virtual-reality navigation decision-making task – the accumulating towers task (ATT) – in which mice integrate pulsatile visual evidence during virtual navigation to make a choice about which way to turn to obtain a reward. Through acute electrophysiological recordings (via Neuropixel probes), we demonstrate that mEC neurons encode both navigational space and accumulated evidence conjointly during the ATT, with firing pattern and speed analyses underlining the possibility that this population of entorhinal conjunctive neurons includes grid cells. Our evidence of conjoint encoding in the entorhinal circuit supplements the growing body of work examining cognitive maps within the hippocampal formation that not only guide us through physical space, but also structure learning, memory, and decision making.