Pyramidal-cell-specific hemispheric asymmetry shapes dorsoventral CA1 dynamics during rest and exploratory behavior

Abstract

The hippocampus is organized along dorsal-ventral and left-right axes, but whether and how these axes interact within defined neuronal populations across behavioral states remains unresolved. Here, we combined within-animal slice electrophysiology with dual-site fiber photometry to compare dorsal and ventral CA1 activity across contralateral hemispheric configurations in mice expressing CaMKII-jGCaMP8s and SynI-jRCaMP1b at distinct longitudinal sites. Ventral CA1 pyramidal neurons exhibited greater intrinsic excitability and stronger AMPAR-mediated synaptic responses than dorsal CA1 neurons. In vivo, CaMKII-defined pyramidal recordings during home cage rest revealed a left-biased event-rate asymmetry within dorsal but not ventral CA1, with no comparable asymmetry in pan-neuronal SynI recordings. Apparent dorsal-ventral differences in spontaneous event rate were therefore configuration-dependent and resolved into a hemispheric, cell-type-specific effect restricted to the CaMKII-defined population. Lead-lag analysis showed that dorsal-ventral temporal coordination was likewise reorganized across configurations and was restricted to pyramidal-cell-biased recordings. During open-field center entries, dorsal CA1 was preferentially recruited before entry across both configurations, whereas non-coordinated entries revealed a relative post-entry suppression of contralateral ventral CA1. Together, these findings suggest that dorsal-ventral CA1 organization cannot be inferred from hemisphere-pooled designs and identify a pyramidal-cell-specific left dorsal CA1 asymmetry as a structural feature that shapes both spontaneous activity and behaviorally driven recruitment along the longitudinal hippocampal axis. Significance StatementThe hippocampus is widely understood to differ along its long axis, with dorsal regions supporting spatial processing and ventral regions supporting emotional behavior. Whether this organization interacts with the left-right axis between hemispheres has remained essentially untested, because most studies pool hemispheres or record unilaterally. Using bilateral fiber photometry in mice, we show that spontaneous activity in dorsal CA1 is left-biased and that this asymmetry is specific to excitatory pyramidal neurons. The asymmetry explains apparent dorsal-ventral differences that appear configuration-dependent under conventional analysis, and it reshapes how dorsal and ventral CA1 are recruited during open-field exploration. These findings reframe hemispheric configuration from a methodological detail into an organizational variable that should be considered when interpreting hippocampal long-axis function.