We take three basic approaches to advancing basic neuroscience.

Together, these can inform and drive future clinical applications.

1 - Circuit neurosciencE

We are dedicated to the investigation of the intersection of emotional regulation, pain, and reward processing. The neural substrates that promote and maintain these processes are often modulated by converging systems.

In particular, our laboratory is interested in the modulatory role of the locus coeruleus noradrenergic system (LC-NE) as a tractable target for clinical intervention. The LC-NE system and its associated circuitry holds promise for interventions in both chronic pain and psychiatric disorders. To move towards these goals we use:

• in vivo optogenetic & chemogenetic manipulations

• in vivo single-unit electrophysiology & calcium imaging

• whole-cell slice electrophysiology for intrinsic and synaptic physiology

• behavioral pharmacology

• anterograde & retrograde neural tract tracing

2 - New Technology for neurosciencE

Technical limitations should not hold back basic or clinical discoveries.

Our laboratory actively pursues the development of new technology to overcome existing limitations to experimental design and access to the mammalian nervous system. In particular we focus on new:

• optoelectronic systems for neural manipulation

• wireless drug & fluid delivery platforms

3 - New behavioral approaches

Animal models have inherent limitations. Leveraging approaches from mathematics, psychology, computer science, machine-learning, and electrical engineering we seek to overcome these limitations.

4 - Brain-wide mechanisms of rapid antidepressants

Traditional antidepressants take several weeks to have beneficial effects. We are particularly interested in understanding the mechanisms underlying fast-acting antidepressants. Here we combine all of the above approaches and more to understand how rapid antidepressants such as electroconvulsive therapy (ECT) and psychedelics globally affect the brain. Collaborating with the Bauer lab, we seek to understand how 5HT2A agonist alter neurovascular coupling. Collaborating with the Majumdar lab we develop new ligands and chemical probes to understand their impact on cells, circuits, and behavior. We also study ethe neurobiological mechanisms that underlie the therapeutic effect of ECT.

Our overarching aim is to uncover underlying mechanisms of these therapeutics to help develop new treatments that provide both rapid onset and enduring relief from neuropsychiatric disorders.