Dissecting the Neural Circuits of Hyperarousal States in Psychiatry

2019 Award: $200,000

Anxiety is a complex state consisting of cognitive, emotional, and physiological components driven by a network across multiple brain regions. In this project, we plan on studying the neural circuits that regulate the hyperarousal state that often precedes the cognitive and emotional changes. Establishing the precise neural circuits involved in hyperarousal is critical to design novel therapeutic interventions for anxiety disorders.

Need/Problem: Anxiety disorders are the most common mental illnesses in the United States, but we still poorly understand how specific neural circuits in the brain are affected during these disorders. Anxiety disorders are often characterized by an amplified arousal response to anxiogenic stimuli (hyperarousal).

Grant Summary: Using pre-clinical mouse models we will use state-of-the-art microscopy techniques to visualize and record the activity of hundreds of individual neurons in real-time while simultaneously assessing arousal responses to identify the neural circuits of hyperarousal.

Goals and Projected Outcomes: This project will help identify specific circuit components that regulate hyperarousal and provide insights into possible pharmacological targets to reduce maladaptive anxiety states. Additionally, these findings will provide strong preliminary data for multiple grant proposals to be submitted to NIH.

Jose Rodriguez-Romaguera, PhD

Grant Details: In the proposed experiments, we aim to assess physiological arousal responses by measuring changes in pupil size, thereby permitting us to easily detect rapid changes in arousal after a mouse is presented with an arousal-inducing stimulus. In parallel, we will examine how activity of these neurons change following a stress-induced hyperarousal state. We hypothesize that new activity patterns will emerge following stress-induction that will allow us to pinpoint critical changes within the neural circuits that regulate anxiety states.