A PROXIMODISTAL GRADIENT OF CA3 PARVALBUMIN<SUP>+ </SUP>INTERNEURON PROPERTIES, MORPHOLOGY AND CONNECTIVITY

The hippocampal cornu ammonis 3 (CA3) region is central to the encoding of novel experiences and the retrieval of memories from partial cues. Previous work has demonstrated pronounced heterogeneity in the connectivity and function of excitatory pyramidal neurons along the proximodistal axis of CA3. Whether a comparable organization exists for parvalbumin-positive interneurons (PVIs), critical regulators of network excitability, remains largely unknown. Here, using in vitro whole-cell patch-clamp recordings from identified CA3 PVIs, we uncovered a gradient of intrinsic properties along the proximodistal axis. Proximal CA3 PVIs exhibited a significantly more depolarized resting membrane potential, increased input resistance, and higher firing frequencies near spike threshold compared to distal CA3 PVIs. To assess potential differences in excitatory input organization, we performed three-dimensional reconstructions of PVI dendrites followed by Sholl-analysis. Proximal PVIs showed increased dendritic branching in stratum lucidum, whereas distal PVIs displayed greater branching in stratum lacunosum moleculare, suggesting differential excitatory inputs from dentate gyrus (DG) and entorhinal cortex (EC), respectively. Accordingly, electrically evoked DG mossy fiber inputs elicited significantly larger excitatory synaptic currents in proximal PVIs. Interestingly, synaptic facilitation at high frequencies (20 and 50 Hz) was significantly greater at distal mossy fiber–PVI synapses. Optogenetic activation of EC projections revealed that feedforward EC excitation of CA3 PVIs is predominantly mediated via polysynaptic local excitatory circuits. In the presence of TTX/4-AP, weak monosynaptic EC inputs persisted but appeared stronger in distal CA3. Together, these findings demonstrate a heterogeneity of CA3 PVI properties, suggesting region-specific contributions to mnemonic computations within CA3.