Neural circuit-selective, multiplexed pharmacological targeting of prefrontal cortex-projecting locus coeruleus neurons drives antinociception.

ABSTRACT: Selective manipulation of neural circuits using optogenetics and chemogenetics holds great translational potential but requires genetic access to neurons. Here, we demonstrate a general framework for identifying genetic tool-independent, pharmacological strategies for neural circuit-selective modulation. We developed an economically accessible calcium imaging-based approach for large-scale pharmacological scans of endogenous receptor-mediated neural activity. As a testbed for this approach, we used the mouse locus coeruleus due to the combination of its widespread, modular efferent neural circuitry and its wide variety of endogenously expressed GPCRs. Using machine learning-based action potential deconvolution and retrograde tracing, we identified an agonist cocktail that selectively inhib

SUBMITTER: Kuo CC 

PROVIDER: S-EPMC11185789 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature