Conditional Deletion of CB1 Receptor in Parvalbumin-Expressing GABAergic Neurons Results in Hearing Loss and Abnormal Auditory Brainstem Response in Mice

Abstract

Cannabinoid receptors 1 (CB1Rs) are widely expressed throughout the central auditory system and play important roles in synaptic plasticity, auditory function, and development. However, the specific functions of CB1Rs in distinct neuronal subtypes in the central auditory system remain largely unclear. In the current study, we investigated whether CB1R deficiency in the parvalbumin (PV)-expressing interneurons, a major class of GABAergic interneurons, affects hearing function. We first systematically examined the neuronal localization and distribution of CB1Rs in the mouse central auditory system using double-label immunofluorescence and confocal laser scanning microscopy. Our findings revealed that CB1Rs are widely distributed across various auditory nuclei, with especially high expression levels observed in the cochlear nucleus (CN), superior olivary complex (SOC), and lateral lemniscus (LL). Furthermore, we established a genetic mouse model for conditional CB1R knockout specifically in PV interneurons, and performed auditory brainstem response (ABR) tests to measure the effects of this deletion on hearing. Surprisingly, the analysis of the ABR revealed that conditional deletion of CB1Rs specifically from PV interneurons elevated hearing threshold at 32 kHz, prolongated the latency of Wave 1, and decreased the amplitudes of Waves 1–4. Our findings provide a solid anatomical foundation for further investigations into the functional roles of CB1Rs in the central auditory system and highlight the critical role of CB1Rs expressed in inhibitory PV interneurons in maintaining normal auditory function.