A sensorimotor brain circuit for transforming aversive experiences into emotional states

Abstract

Innately aversive experiences produce emotional states which control behavior as well as long term associative memories1-3. Brainstem regions engage innate defensive reactions1,3-7, but it is unclear how the nervous system transduces external aversive experiences into higher order, emotional representations in the forebrain to instruct learning and modulate behavior. The prevailing view is that the sensory properties of aversive experiences activate forebrain emotional processing1,3,8-10, but classical theories proposed that internal bodily reactions to unpleasant events produce feeling states11,12. Here we identify a brainstem cuneiform (CnF) circuit which conveys information about both the external sensory causes and internal motor reactions related to aversive events to the lateral/basal nuclei of the amygdala (LA/B), a brain region which stores emotional memories, to enhance ongoing defensive behaviors and regulate associative memory formation. Glutamatergic CnF neurons project directly to LA/B and receive afferent inputs from aversive-sensory and aversive-motor brain regions. Notably, LA/B neurons encode a sensorimotor state in response to noxious stimuli, with both sensory and motor features transmitted through the CnF-to-LA/B pathway. Finally, optogenetic perturbation experiments showed that during aversive experiences, the CnF-LA/B circuit instructs emotional memory formation and enhances the intensity of ongoing defensive behaviors. These findings reveal how the nervous system constructs an aversive sensorimotor state in the amygdala used for regulating the strength of emotional behaviors and producing memory formation. This demonstrates a clinically relevant brain mechanism for the regulation of emotional processing by both external traumatic events and the accompanying bodily reactions.