Functional transition of CA2 pyramidal neurons along the proximodistal axis determines resonance frequency preference

The hippocampal CA2 region has recently been linked to oscillatory activity, spatial navigation, and social behavior. Its predominant neuronal population, CA2 pyramidal neurons (CA2-PNs), critically contributes to hippocampal computations, yet the functional properties along the proximodistal extension of CA2 remain incompletely defined. In organotypic entorhino-hippocampal tissue cultures, we combined PCP4-based localization with single-cell reconstructions and whole-cell patch-clamp recordings to relate neuronal position to structure, synaptic transmission, and intrinsic properties in identified CA2-PNs. Dendritic morphology and spontaneous EPSCs did not correlate with position along the proximodistal axis. By contrast, intrinsic membrane properties, encompassing input resistance, rheobase and action potential metrics, varied gradually. Distal neurons exhibited a pronounced hyperpolarization-induced sag and subthreshold membrane resonance with a frequency preference shifting from delta frequency toward the lower theta range in a subset of cells along the proximodistal axis. Together, these findings reveal location-dependent frequency tuning in CA2 along the proximodistal axis and suggest that a gradient of intrinsic properties sets the conditions for input- and phase-specific recruitment of CA2 during hippocampal network activity.