Hyper-diversity of CRH interneurons in mouse hippocampus

Hippocampal inhibitory interneurons comprise an anatomically, neurochemically and electrophysiologically diverse population of cells that are essential for the generation of the oscillatory activity underlying hippocampal spatial and episodic memory processes. Here, we aimed to characterize a population of interneurons that express the stress-related neuropeptide corticotropin-releasing hormone (CRH) within existing interneuronal categories through the use of combined electrophysiological and immunocytochemical approaches. Focusing on CA1 strata pyramidale and radiatum of mouse hippocampus, CRH interneurons were found to exhibit a heterogeneous neurochemical phenotype with parvalbumin, cholecystokinin and calretinin co-expression observed to varying degrees. In contrast, CRH and somatostatin were never co-expressed. Electrophysiological categorization identified heterogeneous firing pattern of CRH neurons, with two distinct subtypes within stratum pyramidale and stratum radiatum. Together, these findings indicate that CRH-expressing interneurons do not segregate into any single distinct subtype of interneuron using conventional criteria. Rather our findings suggest that CRH is likely co-expressed in subpopulations of previously described hippocampal interneurons. In addition, the observed heterogeneity suggests that distinct CRH interneuron subtypes may have specific functional roles in the both physiological and pathophysiological hippocampal processes.