Studies conducted by the Sweet Lab have been groundbreaking in their direct observation of auditory cortex pathology underlying the in vivo observations of functional impairments. These include reduced pyramidal neuron volume and dendritic spine number within primary auditory cortex. Importantly, we found these impairments of excitatory neurons did not result from neuron loss, nor were they recapitulated by long-term antipsychotic exposure in an animal model. Currently we are evaluating how impairments of protein networks which mediate glutamate signaling to the cytoskeleton may lead to the auditory cortex pyramidal neuron pathology found in schizophrenia. These studies have already identified several proteins that may contribute causally to auditory cortex impairments in this disease, such as Kalirin and ATP1A3. We have also been studying MAP2, a protein that can serve as common downstream hub for pathologic alteration of the cytoskeleton. Importantly for the field, our demonstrations of cellular and molecular pathology within primary auditory cortex firmly excludes a monolithic “top down” viewpoint regarding the origin of auditory impairments in schizophrenia.