Conditional deletion of CB1 receptor in parvalbumin-expressing GABAergic
neurons results in hearing loss and abnormal auditory brainstem response
in mice
Abstract
Cannabinoid receptor 1 (CB1R) is widely expressed in central auditory
system and play important roles in synaptic plasticity and sensory
processing. However, the function of CB1R in specific neuronal subtypes
in the central auditory system is largely unclear. In the current study,
we investigated whether CB1R deficiency in the parvalbumin
(PV)-expressing interneurons, a major class of GABAergic interneurons,
affect hearing function. We fist systematically examined the neuronal
localization and distribution of CB1R in mice central auditory system
using double-label immunofluorescence and confocal laser scanning
microscopy, and found that CB1R showed a wide distribution in the
central auditory system, especially highly expressed in the cochlear
nucleus (CN), superior olivary complex (SOC) and lateral lemniscus (LL).
Furthermore, we established a CB1R conditional knockout mice
specifically in PV interneurons, and measured auditory function using
the auditory brainstem response (ABR) test. Surprisingly, analysis of
ABR indicated that conditional deletion of CB1R specifically from PV
interneurons significantly elevated the physiological hearing threshold,
prolongated the latency of I waves, and decreased the amplitudes of I–V
waves. Collectively, these results indicate that CB1R is highly
expressed in CN and SOC, as well as deleting CB1R specifically from PV
interneurons resulted in partial hearing loss and abnormal brainstem
response. Our finding provides an anatomical basis for further
investigating CB1R’s function in auditory system, and suggest that CB1R
expression in inhibitory PV interneurons is essential for hearing
function.