Spatial Organization of Morpho-Electric Subtypes of Pyramidal Neuron in the Subiculum

The subiculum is a main output structure of the hippocampus, transmitting information from the CA1 to the entorhinal cortex in a spatially structured manner. Prior studies revealed a high electrophysiological and molecular heterogeneity of subicular pyramidal neurons (PYNs) with evidence for further spatial subdivisions of the subiculum. In this study we focused on the cellular organization of the proximal to mid-distal part of the subiculum, designated as subregion 2 (Sub2) and performed a comprehensive electrophysiological and morphological characterization of PYNs by whole-cell patch-clamp recordings combined with intracellular labeling in acute rat hippocampal brain slices. Principal component analysis based on discharge pattern-related parameters and subsequent unsupervised, hierarchical clustering classified the PYNs into three subtypes: regular firing (RF), weak-bursting (WB), and strong-bursting (SB) neurons. Electrophysiological analysis revealed further differences between RF neurons and the two subtypes of bursting neurons in their active and passive properties. The three subtypes also showed differences in their morphometric features, including the apical and basal dendritic spread and branching pattern. Additionally, we identified a divergent morphological subset among RF neurons, bearing two apical dendrites. Mapping the three PYN subtypes onto the subiculum revealed specific spatial distributions along the superficial-deep and proximo-distal axes. Thus, this work maps the heterogeneity of subicular PYN onto differentially distributed subclasses in the Sub2 region with distinct physiological and morphological features. These findings together with prior observations of divergent anatomical projections from subicular subregions are pivotal for the understanding of how subicular morpho-electric neuron types relate to each other and contribute to processing and distribution of information to cortical regions from this hippocampal output region.