Noradrenergic Regulation of central Amygdala in Aversive Pavlovian-to-Instrumental Transfer

Abstract

The neural mechanisms through which a Pavlovian conditioned stimulus (CS) elicits innate defense responses are well understood. But a Pavlovian CS can also invigorate ongoing instrumental responding, as shown by studies of aversive Pavlovian-to-instrumental transfer (PIT). While the neural circuitry of appetitive PIT has been studied extensively, little is known about the brain mechanisms of aversive PIT. We recently showed the central amygdala (CeA) is essential for aversive PIT. In the current studies, using pharmacology and designer receptors in rodents, we demonstrate that noradrenergic activity negatively regulates PIT via brainstem locus coeruleus (LC) activity and LC projections to CeA. Our results provide evidence for a novel pathway through which response modulation occurs between brainstem neuromodulatory systems and CeA to invigorate adaptive behavior in the face of threat.

Significance Statement The results reported herein use Pavlovian-to-instrumental transfer, a test of the motivational value of a CS, to study noradrenergic contributions to aversive motivation. During transfer tests, a shock-paired cue elevates separately trained shock-avoidance responding. Designer receptor excitation of locus coeruleus and its projections to central amygdala before transfer testing eliminated the effect of the cue on shock-avoidance behavior. These findings provide the first evidence that noradrenaline negatively regulates this phenomenon in aversive motivation.