Johns Hopkins School of Medicine

Molecular Neuroanatomy of Brain Reward Circuitry

Brain reward circuitry consists of highly specialized cell types forming complex connections between several cortical and subcortical regions to mediate different aspects of motivated behavior. Dysregulation of brain reward circuitry is a hallmark of several neuropsychiatric disorders, including major depressive disorder and substance use disorders. Our research aims to define the molecular neuroanatomy of key structures in the human brain implicated in reward processing, including the dorsolateral prefrontal cortex, nucleus accumbens, habenula, and amygdala. Using cutting-edge neurobiological techniques, we are directly studying the human brain to identify the molecular identity and spatial relationships of cell populations vulnerable to genetic risk for substance use disorders and other neuropsychiatric disorders to advance the development of therapeutic targets.  To accomplish our goals, we use multi-omic technologies, such as single cell sequencing and spatially-resolved transcriptomics in post-mortem human brain tissue. In addition, we  perform complementary molecular profiling studies in the rodent brain to define the transcriptomic signatures of specific projection neuron classes and activity-induced changes in downstream targets. Our translational approach integrates cell type- and region-specific molecular profiling in the postmortem human brain with circuit-specific molecular profiling in rodent brain to efficiently identify cell types and gene targets for prevention and treatment of brain disorders.