Cell-type-specific manifold analysis discloses independent geometric transformations in the hippocampal spatial code

Abstract

Integrating analyses of genetically defined cell types with population-level approaches remains poorly explored. We investigated this question by focusing on hippocampal spatial maps and the contribution of two genetically defined pyramidal cell types in the deep and superficial CA1 sublayers. Using single- and dual-color miniscope imaging in mice running along a linear track, we found that population activity from these cells exhibited three-dimensional ring manifolds that encoded the animal position and running direction. Despite shared topology, sublayer-specific manifolds displayed distinct geometric features. Manipulating track orientation revealed rotational and translational changes in manifolds from deep cells, contrasting with more stable representations by superficial cells. These transformations were not observed in manifolds derived from the entire CA1 population. Instead, cell-type-specific chemogenetic silencing of either sublayer revealed independent geometric codes. Our results show how genetically specified subpopulations may underpin parallel spatial maps that can be manipulated independently.

Keywords: CA1 sublayers; calbindin; cell types; geometry; manifolds; topology.