Multiplexed pharmacological calcium imaging reveals distinct GPCR-mediated response profiles of locus coeruleus neurons

Abstract ID 23754 Poster Board 169 The noradrenergic neurons in locus coeruleus (LC) are the main source of norepinephrine (NE) for the central nervous system. Potential modular organization of the LC could provide functional differentiation during distinct behaviors. This organization would suggest that different LC modules should act differentially according to the behavioral state. The LC is enriched in many G-protein coupled receptors (GPCRs) that are likely endogenously activated during behavior to regulate activity among LC modules, but the detailed mechanisms remain unclear. Here we perform GCaMP8f calcium imaging of LC-NE neurons in acute brain slices in concert with a large-scale pharmacological scan of multiple GPCR agonists. We use modified image processing algorithms, CNMF-E and CASCADE, for automatic region of interest (ROI) extraction and machine learning-based spike deconvolution, respectively. Approximately five hours of simultaneous cell-attached electrophysiological recordings and calcium imaging are used to train the spike prediction model. This model can deconvolute individual LC-NE action potentials with firing rates below 4 Hz with almost 100% accuracy. Deconvolution accuracy stays about 85% while cells are firing at 5 Hz. In addition, the significantly lower rate (