Doyun Lee
Research Mentor: Jun Kim
Mentor Department: Kresge Hearing Research Insitutue, Medicine
Author(s): Doyun Lee, Jorge Contreras, Jun Hee Kim
Session: Session 4 (1:00 PM – 1:50 PM)
Presentation Type: Poster 17
Abstract
Autism Spectrum Disorder (ASD) is frequently associated with abnormal sensory processing, including hypersensitivity or hyposensitivity to auditory stimuli. However, the mechanisms underlying these abnormalities in sensory processing remain unclear. The endocannabinoid system plays an important role in maintaining homeostasis and regulating neuronal activity, and disruption of cannabinoid signaling has been implicated in neurodevelopmental disorders. Cannabinoid receptor type 1 (CB1R) is broadly expressed throughout the central auditory pathway, but its contribution to auditory brainstem function has not been well defined. In this study, we investigate the role of CB1R in sound-evoked neuronal excitability in the auditory brainstem, using CB1R knockout mouse (Cb1r-/- ), which has been shown to have ASD-like behaviors, such as reduced social interaction and repetitive grooming. Here, we aim to further explore the CB1R’s function on the auditory brainstem. To assess the tone hearing ability of the mice, we used the distortion product otoacoustic emissions (DPOAE) test. We found a decrease in distortion products in Cb1r-/- compared to Cb1+/+ in male (p=0.0207) and female mice (p=0.0388). To assess neuronal activity in the medial nucleus of the trapezoid body (MNTB), an important auditory nucleus involved in sound sensitivity, mice were placed into sound-attenuated chambers and given low frequencies (8 kHz). Sound-evoked neuronal activation was measured through the expression of c-Fos, using immunohistochemistry. Comparisons were made between Cb1r-/- and wild-type (Cb1r+/+ ) mice of either sex. Our results show that there is a significant increase in c-Fos+/MAP2+ principal neurons of Cb1r-/- mice compared to Cb1r+/+ mice (p= 0.0027) after tone stimulation at low frequency (8 kHz). In addition, the spatial pattern of activated neurons was altered, consistent with disruption of tonotopic organization within the MNTB in Cb1r-/- mice compared to Cb1r+/+ mice. These findings indicate that CB1R is required for proper regulation of sound-evoked activity and tonotopic precision in the auditory brainstem. Overall, our study identifies CB1R-dependent endocannabinoid signaling as a potential circuit mechanism underlying auditory processing disorder and sensory dysfunction in ASD.
