EARLY POSTNATAL CHANGES IN CCK+ BASKET CELL SYNAPTIC CONNECTIVITY AND EXCITABILITY IN CA1 HIPPOCAMPAL CIRCUITS

Adult hippocampal functions rely on the precise synaptic organization and wiring of local CA1 circuits. During early postnatal development, CA1 activity undergoes a major transition by which interneurons remain activated by self-generated movements, while most pyramidal neurons are silenced. This transition coincides with a rapid developmental rise in perisomatic inhibition that functionally disengages CA1 neural dynamics from external inputs. However, the cell-type-specific inhibitory mechanisms underlying this transition are poorly understood. Cholecystokinin-expressing basket cells (CCKBCs) emerge as strong candidates, yet gaining genetic access to this cellular population during early postnatal stages remains challenging. Here, we implement a cell-type-specific viral strategy in SNCG-IRES2-Flp mice to selectively target and label CCKBCs at birth (P0). Using patch-clamp paired recordings ex vivo between postnatal days P6–P14, we next examined the development of intrinsic excitability and synaptic connectivity between CCKBCs and CA1 pyramidal neurons, complemented by morphological reconstruction of recorded pairs. By the second postnatal week, CCKBCs demonstrate progressive intrinsic maturation: hyperpolarizing resting potential, decreased input resistance, faster membrane time constant, increased capacitance, faster action potential waveform, and higher firing rates. Despite this intrinsic maturation, CCK+ synaptic connectivity remains unexpectedly low, indicating a phase of delayed or selective functional integration as synaptic connections are refined between the P6-P14 window. Together, these findings reveal a dissociation between intrinsic maturation and synaptic integration of CCKBCs in developing CA1 circuits, suggesting that early CCK-mediated inhibition plays a modulatory role distinct from the precisely timed inhibition of parvalbumin-expressing basket cells (PVBCs).