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

Area of Science:

• Neuroscience
• Systems Neuroscience
• Computational Neuroscience

Background:

• The hippocampus exhibits functional specialization along its dorsal-ventral axis (spatial vs. emotional processing).
• Interactions between the dorsal-ventral and left-right hippocampal axes remain poorly understood due to methodological limitations.

Purpose of the Study:

• To investigate how dorsal-ventral and left-right hippocampal axes interact within specific neuronal populations.
• To determine if hemispheric configuration influences observed dorsal-ventral functional differences.

Main Methods:

• Combined slice electrophysiology and dual-site fiber photometry in mice.
• Compared dorsal and ventral CA1 activity across different contralateral hemispheric configurations.
• Utilized CaMKIIα-jGCaMP8s and SynI-jRCaMP1b reporters for cell-type-specific recordings.

Main Results:

• Ventral CA1 pyramidal neurons showed higher excitability and synaptic responses than dorsal CA1.
• A left-biased event-rate asymmetry was observed in dorsal CA1 pyramidal neurons, but not ventral CA1 or pan-neuronal populations.
• Hemispheric configuration significantly altered apparent dorsal-ventral differences in spontaneous activity and temporal coordination.
• Dorsal CA1 was preferentially recruited before open-field center entries, with contralateral ventral CA1 suppressed post-entry.

Conclusions:

• Dorsal-ventral hippocampal organization cannot be reliably inferred from hemisphere-pooled studies.
• A pyramidal-cell-specific left dorsal CA1 asymmetry is a key organizational feature shaping hippocampal function.
• Hemispheric configuration is a critical variable for interpreting hippocampal long-axis function.