Abstract

Calcium-permeable Kainate and AMPA receptors (CP-KARs and CP-AMPARs) are critical mediators of synaptic plasticity and excitability, particularly in inhibitory GABAergic interneurons. This study aimed to visualize and characterize the electrophysiological properties and functional roles of GABAergic hippocampal neurons that express these unique receptor subtypes. Using a combination of advanced fluorescent imaging techniques and whole-cell patch-clamp electrophysiology in hippocampal slices and cultured neurons, we successfully identified and isolated this specific neuronal population. Our findings reveal that these GABAergic neurons exhibit distinct membrane properties, including a faster firing rate and a reduced sensitivity to GABA-A receptor-mediated inhibition compared to interneurons lacking these receptors. Functionally, the presence of CP-KARs and CP-AMPARs in these interneurons significantly modulates their excitability and, consequently, their inhibitory output onto principal cells. Specifically, the high calcium permeability of these receptors facilitates a rapid, activity-dependent regulation of the inhibitory circuit. These results suggest that GABAergic neurons expressing CP-KARs and CP-AMPARs play a pivotal role in regulating hippocampal network activity and may represent a key mechanism for controlling hyperexcitation, with implications for understanding neurological disorders such as epilepsy and ischemia. The visualization and detailed characterization of this neuronal subtype provide a foundation for future targeted pharmacological interventions.