Neural Circuit Encoding of Arousal and Anxiety
Psychiatric disorders are often characterized by rapid and amplified arousal response to stimuli (hyperarousal), which is often followed by a motivational drive to avoid such stimuli. When exposed to arousing images with negative emotional valence, humans show an increase in both arousal responses and neural activity within the amygdala, a brain region known to be involved in motivation and emotional regulation. The amygdala has multiple sub-nuclei and many genetically identifiable neuronal populations. Functional imaging studies in humans have provided crucial evidence linking amygdala activity to changes in arousal states. However, they lack the temporal resolution needed to assess how brain activity relates to rapid arousal responses or the spatial resolution to track the activity of individual neurons. In contrast, animal models can shed light on the relationship between arousal and its underlying neural substrates.
Preclinical Models of Disease
The primary goal of our lab is to dissect the neuronal circuits that drive hyperarousal states by monitoring neuronal activity with single-cell precision using mice as a model system. To accomplish this goal, our laboratory in the Neuroscience Center at UNC uses state-of-the-art in vivo calcium imaging techniques in both head-fixed (two-photon microscopy) and freely-moving (miniscope) mice to record and track the activity of hundreds of individual neurons with both genetic and projection specificity. Complementary to these imaging approaches we also employ in vivo optogenetic approaches to directly manipulate the activity of these neurons. These approaches allow us to record and manipulate the activity of individual neurons while simultaneously assessing arousal and behavioral responses.
Our lab also develops technology that will allow us to better understand the neurocircuitry of arousal and anxiety. For our behavioral studies, we employ an approach of building and designing behavioral tasks and tools tailored to determine specific circuit functions. To accomplish these goals we collaborate with the laboratory of Dr. Nicolas Pégard in developing and validating optical instrumentations to track and manipulate neurons with single-cell precision, as well as improve readouts of physiological arousal responses.
We further aim to extend and translate the insights gained from our rodent models to human studies within the Carolina Stress Initiative (CSI), a translational program that Dr. Rodriguez-Romaguera co-directs with clinician-scientist Dr. Anthony Zannas within the UNC Department of Psychiatry. The CSI aims to unravel how dysfunctional brain circuits and related epigenetic changes lead to trauma and stress-related diseases. The ultimate goal of CSI is to translate our findings into novel interventions for patients suffering from trauma and stress-related disorders. Our lab is also part of the Carolina Institute for Developmental Disabilities (CIDD). With colleagues from the CIDD (Drs. Grzadzinki, Dichter, Hazlett & Piven) we aim to extend our insights from our rodent models to unravel how impairments in brain development can lead to dysfunctional arousal functioning in neurodevelopmental disorders, such as autism spectrum disorders.