Cell-type-specific enhancement of deviance detection by synaptic zinc in the mouse auditory cortex

Stimulus-specific adaptation is a hallmark of sensory processing in which a repeated stimulus results in diminished successive neuronal responses, but a deviant stimulus will still elicit robust responses from the same neurons. Recent work has established that synaptically released zinc is an endogenous mechanism that shapes neuronal responses to sounds in the auditory cortex. Here, to understand the contributions of synaptic zinc to deviance detection of specific neurons, we performed wide-field and 2-photon calcium imaging of multiple classes of cortical neurons. We find that intratelencephalic (IT) neurons in both layers 2/3 and 5 as well as corticocollicular neurons in layer 5 all demonstrate deviance detection; however, we find a specific enhancement of deviance detection in corticocollicular neurons that arises from ZnT3-dependent synaptic zinc in layer 2/3 IT neurons. Genetic deletion of ZnT3 from layer 2/3 IT neurons removes the enhancing effects of synaptic zinc on corticocollicular neuron deviance detection and results in poorer acuity of detecting deviant sounds by behaving mice.