Research

What technological innovations can expand our ability to probe neural circuits and brain-body physiology?

Technology is driving neurobiology into uncharted territories, revealing and altering brain circuits like never before. In collaboration with others and through our own efforts, we’re constantly exploring what new techniques can advance brain research.

Working with Michal Lipson’s group, we developed a nanophotonics probe, a reconfigurable optical interface that enables high-density neural stimulation in freely moving rodents (Mohanty et al., 2020). With Song Hu’s team, we are creating an optical fiber technique capable of stimulating over 1,000 sites with a single fiber. A persistent challenge in unbiased neural targeting is the tropism of viruses—how specific viruses preferentially infect certain cell types. To address this, we improved viral tracing methods for the CAV2 retrograde virus (Li et al., 2018), and we continue to explore new approaches to expand the frontiers of neurotechnology.

What role does the brain play in immunology and diseases like cancer and autoimmune disorders?

We initiated research exploring brain-body interactions, focusing on how the brain communicates with the immune system. We identified a circuit by which cancer-induced inflammation leads to fatigue and depressive symptoms, providing insights into chronic inflammation’s impact on behavior (Starosta et al., under review). Our studies mapped connections from sympathetic nerves to breast tumors, demonstrating how sympathetic activation increases tumor growth (Monje et al., 2020, Cell). We are also investigating rheumatoid arthritis and endometriosis to understand neuro-immune mechanisms affecting behavior and disease.

How do neuromodulators like dopamine and acetylcholine influence behavior and mental health?

Neuromodulators can reconfigure circuit operations; we are focusing on the cholinergic basal forebrain and midbrain dopamine systems. Our research explores the computations of neuromodulatory systems, focusing on the cholinergic basal forebrain and midbrain dopamine systems. Recent studies have expanded into the modularity of the midbrain dopamine system and its coordination with the cholinergic system.

We investigated how elevated dopamine levels contribute to high-confidence false perceptions, offering insights into the neural mechanisms underlying psychotic disorders. This work demonstrates dopamine’s causal role in hallucination-like perception (Schmack et al., 2021, Science).

Currently we are dissecting the functions of striatal region-specific roles of midbrain dopamine and probing the dopamine in the context of psychosis and Parkinson’s disease.