Dynamic Hippocampal CA2 Responses to Contextual Spatial Novelty

Abstract

Hippocampal place cells are functional units of spatial navigation and are present in all subregions: CA1, CA2, CA3, and CA4. Recent studies on CA2 have indicated its role in social and contextual memories, but its contribution to spatial novelty detection and encoding remains largely unknown. The current study aims to uncover how CA2 processes spatial novelty and to distinguish its functional role towards the same from CA1. Accordingly, a novel 3-day paradigm was designed where animals were introduced to a completely new environment on the first day, and on subsequent days, novel segments were inserted into the existing spatial environment while the other segments remained the same, allowing us to compare novel and familiar parts of the same closed-loop track on multiple days. We found that spatial novelty leads to dynamic and complex hippocampal place cell firings at both individual neuron and population levels. Place cells in both CA1 and CA2 had strong responses to novel segments, leading to higher average firing rates and increased pairwise cross correlations across all days. However, CA2 place cells that fired for novel areas had lower spatial information scores than CA1 place cells active in the same areas. At the ensemble level, CA1 only responded to spatial novelty on day 1, when the environment was completely novel, whereas CA2 responded to it on all days, each time novelty was introduced. Therefore, CA2 was more sensitive and responsive to novel spatial features even when introduced in a familiar environment, unlike CA1.