Flexible function: Interneuron contributions to cortical circuits in health and disease


April 19, 2016 - 12:00pm
Northwest 243
About the Speaker
Jess Cardin (Yale)

Spontaneous and sensory-evoked cortical activity is highly state-dependent, promoting the functional flexibility of cortical circuits. We find that arousal and motor activity have complementary roles in regulating cortical operations, providing dynamic control of sensory encoding. Although these relationships have been explored in the healthy brain, little is known about their dysregulation in neurodevelopmental disorders such as schizophrenia. Schizophrenia is associated with altered cognitive and perceptual processing, functions served by the cortex, as well as dysregulation of normal brain rhythms such as gamma oscillations (20-80Hz). Current evidence suggests that dysregulation of GABAergic interneurons contributes to neural and behavioral deficits in this disease. However, the roles of diverse interneuron populations in psychiatric disease remain explored. Neuregulin 1 (NRG1) and its interneuron-specific receptor ERBB4 are risk genes for schizophrenia. Using an ErbB4 deletion model, we tested the role of three distinct interneuron populations in disease-related deficits. Mice lacking ErbB4 demonstrate impaired visual learning and task performance and compromised visual cortex function. In contrast to the prevailing view, which supports a role for parvalbumin (PV)-expressing interneurons, we find that deletion of ErbB4 specifically from vasoactive intestinal peptide (VIP)-expressing interneurons mediates many of the observed phenotypes. Mice in which VIP interneurons lack ErbB4 show altered cortical gamma-range LFP activity, elevated firing rates, and reduced fidelity of visual sensory encoding. Importantly, ErbB4 deletion from these interneurons abolishes the behavioral state-dependence of cortical activity and profoundly reduces the impact of arousal on the signal:noise of visual responses. Our data support a novel role for VIP interneurons in the pathophysiology of schizophrenia and provide a new perspective on the disruption of cortical circuit function in this complex disease.