Calbindin-expressing CA1 pyramidal neurons encode spatial information more efficiently.

Hippocampal pyramidal neurons (PNs) are traditionally conceptualized as homogeneous population. For the past few years, cumulating evidence has revealed the structural and functional heterogeneity of hippocampal pyramidal neurons. But the in vivo neuronal firing pattern of molecularly identified pyramidal neuron subclasses is still absent. In this study, we investigated the firing patterns of hippocampal PNs based on different expression profile of Calbindin (CB) during a spatial shuttle task in free moving male mice. We found that CB+ place cells can represent spatial information more efficiently than CB- place cells, albeit lower firing rates during running epochs. Furthermore, a subset of CB+ PNs shifted their theta firing phase during rapid-eye-movement (REM) sleep states compared to running states. Although CB- PNs are more actively engaged in ripple oscillations, CB+ PNs showed stronger ripple modulation during slow-wave sleep (SWS). Our results pointed out the heterogeneity in neuronal representation between hippocampal CB+ and CB- PNs. Particularly, CB+ PNs encode spatial information more efficiently, which might be contributed by stronger afferents from the lateral entorhinal cortex to CB+ PNs. Significance Statement Pyramidal neurons (PNs) in the hippocampus show heterogeneity along the longitudinal axis. But deep and superficial layer PNs are difficult to identify with traditional tetrode recordings. Combining with optogenetic tools, we were able to identify and record ephys patterns of CB+ PNs in free moving mice.We found that CB+ place cells represent spatial information more efficiently in a spatial shuttle task, with more spikes fired inside than outside of place fields, and carrying more spatial information per spike compared to CB- peers. We also found heterogeneity of neuronal firing dynamics of hippocampal PN subtypes with respect to theta and ripple oscillations.These results suggest that we take into consideration such heterogeneity of PNs in future investigations of hippocampal function.