Gordon Lab

Systems Neuroscience Approaches to Psychiatric Disease

Cloning of genes which predispose to neuropsychiatric illness is proceeding rapidly of late. Yet identifying such predisposition genes is but a first step in understanding the pathophysiology of mental illnesses. We study genetic models of these diseases from an integrative neuroscience perspective with a focus on understanding how a given disease mutation leads to a behavioral phenotype in disease-related mouse models. To this end, we employ a range of systems neuroscience techniques, including in vivo anesthetized and awake behaving recording, neuroanatomical tracing, and pharmaco- and optogenetics. Current efforts are focused in two main disease areas: schizophrenia, and anxiety.

Of relevance to schizophrenia, we are attempting to understand the neural circuitry underlying spatial working memory in normal mice, and its disruption in mice carrying mutations which in humans predispose to schizophrenia. In particular, in collaboration with Drs. Joseph Gogos and Maria Karayiorgou, we are exploring the mechanisms underlying disruption of hippocampal-prefrontal synchrony in a mouse model of the 22q11 microdeletion syndrome.

With regard to anxiety, we have implicated a circuit including the ventral hippocampus and medial prefrontal cortex in the genesis of innate anxiety-like behavior in normal mice. Activity in this circuit is enhanced in mice lacking the serotonin 1A-receptor, a model of genetic predisposition to anxiety. Current experiments are aimed at understanding whether and how this circuit interacts with the amygdala and other brain regions known to play important roles in anxiety behaviors.