Fig. 7. Genetically defined norepinephrine subpopulations project to unique sets of targets.

Selected axonal projections from r-derived norepinephrine neuron subpopulations located in the brainstem are illustrated as colored lines on a schematic of the adult mouse brain compressed along the mediolateral axis. Approximate positions of the subpopulations from which the projections originate are illustrated as colored circles (bottom panel). Thickness of the colored lines encircling target regions of interest qualitatively represent the density of innervation from the genetically defined subpopulation of the same color (r1 purple; r2 orange; r3&5 yellow; r4 blue). r1(En1^cre)-derived neurons (purple) project throughout the neuroaxis, providing the most dense innervation to regions involved in higher order cognition and sensory perception, including the cortex (Ctx), thalamus (Thal), and hippocampus (Hippo). r2(Hoxa2-cre)-derived norepinephrine neurons (orange) project to limited targets, including a sparse projection to the somatosensory cortex (Ctx somato) and the cerebellum (Cereb). Projections from r3&5(Krox20^cre)-derived norepinephrine neurons (yellow) are restricted to the hindbrain, including a sparse to moderate input to the parabrachial nucleus (PBN) and Cereb, as well as a substantial input to the NTS. r4(Hoxb1^cre)-derived norepinephrine neurons (blue) project to key components of the central autonomic nervous system, including regions of the amygdala (Amyg), hypothalamus (Hyp), bed nucleus of the stria terminalis (BNST), and insular cortex (Ctx ins).