DG\u2013CA3 circuitry mediates hippocampal representations of latent information

Alexandra T. Keinath,Andrés Nieto-Posadas,Mark P. Brandon,Jennifer C. Robinson

doi:10.1038/s41467-020-16825-1

Abstract

Survival in complex environments necessitates a flexible navigation system that incorporates memory of recent behavior and associations. Yet, how the hippocampal spatial circuit represents latent information independent of sensory inputs and future goals has not been determined. To address this, we image the activity of large ensembles in subregion CA1 via wide-field fluorescent microscopy during a novel behavioral paradigm. Our results demonstrate that latent information is represented through reliable firing rate changes during unconstrained navigation. We then hypothesize that the representation of latent information in CA1 is mediated by pattern separation/completion processes instantiated upstream within the dentate gyrus (DG) and CA3 subregions. Indeed, CA3 ensemble recordings reveal an analogous code for latent information. Moreover, selective chemogenetic inactivation of DG–CA3 circuitry completely and reversibly abolishes the CA1 representation of latent information. These results reveal a causal and specific role of DG–CA3 circuitry in the maintenance of latent information within the hippocampus.

Highlights

Survival in complex environments necessitates a flexible navigation system that incorporates memory of recent behavior and associations
We imaged the calcium dynamics of large populations of CA1 neurons using a miniaturized head-mounted wide-field microscope as mice freely explored this environment for 20 min[14,15] (Fig. 1b; n = 6 mice, one mouse excluded for persistent entryway behavioral bias, n = 5 analyzed, 29 sessions; Supplementary Fig. 1, Supplementary Table 1)
Characterizing the neural basis of navigation has been a major focus of research since the discovery of hippocampal place cells; yet a mechanistic explanation of how hippocampal spatial circuits represent information beyond sensory inputs and goal-oriented behavior has been limited, likely hindered by difficulties assaying latent information isolated from a behavioral task

Summary

Introduction

Survival in complex environments necessitates a flexible navigation system that incorporates memory of recent behavior and associations. Selective chemogenetic inactivation of DG–CA3 circuitry completely and reversibly abolishes the CA1 representation of latent information These results reveal a causal and specific role of DG–CA3 circuitry in the maintenance of latent information within the hippocampus. A flexible navigational system should encode aspects of the current context beyond immediate sensory input and future goals Latent information, such as a memory of recent behavior or experiences independent of future goals, can be especially important for discovering and representing relationships that extend beyond the capacity of immediate sensory information. We show that hippocampal subregions CA1 and CA3 represent latent information through changes in firing rate during unconstrained 2D navigation in a novel behavioral paradigm in the absence of explicit task demands. These results demonstrate a causal and specific role of DG–CA3 circuitry in the representation of latent information during unconstrained navigation

Methods

Results

Conclusion