Viscerosensory activation of noradrenergic inputs to the amygdala in rats

Norepinephrine (NE) acts in the amygdala to regulate processes underlying acquisition and expression of emotional learning. The present study investigated whether stimulation of gastric vagal sensory afferents activates neurons immunoreactive for the NE synthetic enzyme, dopamine beta hydroxylase (DbetaH), in medullary and pontine cell groups that innervate the central nucleus of the amygdala (CeA) in rats. To identify such neurons, retrograde neural tracers were microinjected bilaterally into the CeA. Seven to 10 days later, rats were injected intraperitoneally with saline vehicle (controls) or cholecystokinin octapeptide (CCK, 10 microgram/kg) to stimulate gastric vagal afferents, then perfused with fixative 60-90 min later. Brain sections were processed for localization of neural tracer and cFos protein (to identify activated cells). Approximately 30% of retrogradely labeled neurons in the nucleus of the solitary tract (NST, A2/C2 region) and 19% of retrogradely labeled neurons in the ventrolateral medulla (VLM, A1/C1 region) were activated in rats after CCK treatment. Triple immunolabeling of cFos, neural tracer, and DbetaH confirmed that the large majority of activated, CeA-projecting neurons were noradrenergic (or adrenergic). Conversely, CCK activated less than 4% of CeA-projecting neurons in the locus coeruleus (LC, A6 cell group), similar to control cases. These findings suggest that vagal afferent stimulation may modify amygdalar processes of emotional learning via direct noradrenergic/adrenergic projections from the caudal medulla to the CeA.