Eric Zimmerman

Corticothalamic gating of dopamine neuron firing: relevance to psychosis

Schizophrenia is a prevalent and debilitating mental illness. The psychotic or “positive” symptoms of the disease can sometimes be addressed by treatment with antipsychotic medications. However, antipsychotic medications are plagued by limited effectiveness and robust side effect profiles. The fact that antipsychotic medications act by blocking dopamine (DA) receptors, along with other lines of evidence, suggests that the psychotic symptoms of schizophrenia might be caused by excess DA release in the brain. It has been proposed that this DA excess could be caused by dysfunction in afferent regions governing ventral tegmental area (VTA) DA neuron activity. However, these regions have not been fully characterized. My project is therefore designed to enhance our knowledge of the afferent regions involved in controlling activity of VTA DA neurons, and which of these afferent regions could contribute to the aberrant neurobiology seen in schizophrenia. I have addressed this question using preclinical rodent models in in vivo, circuit-based electrophysiological and behavioral approaches. In this talk, I will present data demonstrating that the nucleus reuniens of the midline thalamus (RE) is a novel region involved in the control of VTA DA neuron firing. RE is a higher-order thalamic nucleus known to facilitate communication between prefrontal cortex and hippocampus, but its role in controlling DA tone has yet to be explored. My data suggest that RE drives VTA DA neuron firing via connections with the ventral hippocampus, and also acts to gate the influence of the medial prefrontal cortex on VTA DA neurons. I will also discuss the potential relevance of these findings to the pathophysiology of schizophrenia.