EXACERBATED TOP-DOWN THALAMOCORTICAL INPUTS TO AUDITORY CORTEX IN A SCHIZOPHRENIA MOUSE MODEL

Accurate sensory perception is an active process requiring the integration of sensory (i.e., bottom-up) and internally-generated (i.e., top-down) information, and is impaired in psychiatric disorders such as schizophrenia (SCZ), where auditory disturbances are a hallmark. Theoretical models have proposed that an imbalance between bottom-up and top-down inputs processing might be involved in SCZ-related pathology but if and how this is implemented in auditory circuits is unclear. We have previously shown that the higher-order auditory thalamus (HOAT) sends top-down memory-related information to secondary auditory cortex (AuV). Here, we evaluate how HOAT projections to AuV are affecting the processing of sensory information arising from primary auditory cortex (A1) in wild-type mice (WT) and in a mouse model of the 22q11.2 microdeletion, the highest known genetic risk factor for developing SCZ. To do so, we combined behavior, optogenetics and electrophysiological recordings of layer 5 pyramidal neurons in response to afferent stimulation of A1 and HOAT inputs in acute brain slices. We show that higher-order auditory thalamocortical circuits display an increased excitation/inhibition balance in 22q11.2 mice, concomitant to an increase in spiking probability compared to WT mice. Interestingly, this is correlated with auditory-gating impairments. These differences are mediated by a stronger widespread direct connectivity from the HOAT to local cortical neurons in AuV, highlighting a novel sensory circuit mechanism that could explain perceptual disturbances in schizophrenia pathology.