CALCIUM ACTIVITY OF LAYER 5 PYRAMIDAL NEURONS OF MICE PRIMARY AUDITORY CORTEX IS ALTERED BY NOISE OVEREXPOSURE

Loud noise can induce tinnitus by affecting the auditory system at multiple levels. However, whether activity dynamics of the primary auditory cortex (A1) in response to sound and silence is altered by previous noise overexposure is less known. Recently we showed that subtypes of layer 5 pyramidal neurons (L5PNs) of A1 have modified firing frequencies 1 week after loud noise exposure in slice recordings. Here, we use a genetically encoded calcium indicator (CamKII2a-GCaMP6f) and an implanted lens-prism system to image A1 L5PNs in vivo. Recordings were done before and 1 week after loud noise overexposure (4-18kHz, 90dB, 1.5 hr followed by 1.5 hr in silence) in mice (n = 4) using a head-fixed miniature microendoscope (UCLA V3). The sound protocol consisted of 30 s tones (2-20 kHz), interleaved with 30 s of silence. Preliminary analysis of calcium signals from 422 L5PNs identified the same neurons (n = 172) of both sessions by filtering the center of mass positions across sessions using cartesian adjustments. Next, threshold adjusted calcium activity showed that 50.6% (85/172) of cells increased neuronal activity while 49.4% (87/172) decreased activity 1 week after noise overexposure. Interestingly, some L5PNs also increased activity during silence (30/172). Neuronal activity patterns were clustered using K-means and the closest means showed 3 main activity patterns (decrease; increase by duration of stimuli; increase to particular frequencies). This study describe how noise overexposure can change output dynamics of the descending auditory system that may be part of mechanisms leading to noise-induced tinnitus.