Defining modulatory inputs into CNS neuronal subclasses by functional pharmacological profiling

摘要: Previously we defined neuronal subclasses within the mouse peripheral nervous system using an experimental strategy called “constellation pharmacology.” Here demonstrate broad applicability of constellation pharmacology by extending it to CNS and specifically ventral respiratory column (VRC) brainstem, a region containing network controlling rhythm. Analysis dissociated cells from this locus revealed three major cell classes, each encompassing multiple subclasses. We broadly analyzed combinations (constellations) receptors ion channels expressed VRC classes These were strikingly different constellations found in neurons dorsal root ganglia. Within population, subset responded substance P, putatively corresponding inspiratory pre-Botzinger complex (preBotC) neurons. Using pharmacology, that these P-responsive also histamine, about half bradykinin. Electrophysiological studies conducted brainstem slices confirmed preBotC responsive P exhibited similar responsiveness bradykinin histamine. The results predictive utility for defining modulatory inputs into specific central networks.