Lisa Gunaydin, PhD
Circuit basis of motivated behaviors in psychiatric disease
Psychiatric disorders were historically thought to arise from a brain-wide chemical imbalance in neurotransmitter levels, but it is now becoming clear that they involve much more complex and subtle alterations in neural dynamics across specific synapses and networks in the brain. Our lab aims to understand the neural circuits underlying motivated behaviors and how they are perturbed in psychiatric diseases such as anxiety, autism, and obsessive-compulsive disorder (OCD).
Because it is challenging to model complex human psychiatric disorders in their entirety in mice, we focus on discrete behavioral symptom domains that are tractable in rodents, such as social interaction, compulsive/repetitive behavior, and anxiety assays based on exploration and approach-avoidance conflict. Mechanisms underlying each of these fundamental behaviors are relevant to a broad range of human disorders (e.g. repetitive behavior is a symptom of both autism and OCD).
We are specifically interested in how top-down projections from the prefrontal cortex regulate subcortical areas involved in emotional behaviors. To address these questions we employ a combination of rodent behavioral assays, optogenetics, and neural recording. We focus on optical recording approaches such as fiber photometry, which allows us to record the activity of genetically defined cells and axonal projections in a behaving animal. This multifaceted approach allows us to 1) correlate endogenous patterns of cell type- and projection-specific neural circuit activity with specific behaviors, 2) manipulate these same circuits using optogenetic stimulation and inhibition to determine their causal role in behavior, and 3) use these basic scientific insights to guide targeted circuit manipulation as a way to ameliorate pathological behaviors in disease models.
- Cortico-striatal modulation of anxiety-like behavior and implications for chronic therapeutic stimulation
- Dissociating roles of projection-defined cortical subpopulations in distinct behavioral symptoms of OCD (anxiety and compulsive behavior)
- Mechanisms and rescue of cellular and circuit deficits in genetic mouse models of OCD and autism