Drug addiction is a chronic, relapsing brain disorder characterized by compulsive drug seeking and use despite harmful consequences. Maladaptation of the brain reward system, including the midbrain dopamine neurons and their projection targets such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC), is believed to underlying addictive behavior. However, the neuronal heterogeneity and complex connections of the brain reward system prevented a deeper understanding of the drug addiction mechanisms. Using single cell transcriptome analysis (scRNA-seq), we classified the neuron subtypes. By monitoring the transcriptome dynamics of neuron subtypes during the process of addiction development using a clinically relevant intravenous self-administration (IVSA) mouse model, we identified relevant neuron subtypes. The role of the relevant neuron subtypes in the addiction behavior were tested by chemogenetic and optogenetic approaches. Key regulators of the transcriptional changes in the relevant neuron subtypes were identified and characterized through molecular analysis using purified neuron subtypes. Our study provides a broadly applicable strategy for understanding the molecular, cellular and circuitry mechanism of drug addiction and other psychiatric diseases.
Xiaoke Chen, Associate Professor of Biology, Stanford University
Pre-Seminar March 3rd, 2020 at 4:00 PM in Clark S361