Abstract
Sensory information is transmitted from peripheral nerves, through the spinal cord, andup to the brain. Sensory information may be modulated by projections from the brain tothe spinal cord, but the neural substrates for top-down sensory control are incompletelyunderstood. We identified a novel population of inhibitory neurons in the mousebrainstem, distinguished by their expression of prodynorphin, which we named LJA5.Here, we identify a similar group of Pdyn+ neurons in the human brainstem, and we definethe efferent and afferent projection patterns of LJA5 neurons in mouse. Using specificgenetic tools, we selectively traced the projections of the Pdyn-expressing LJA5 neuronsthrough the brain and spinal cord. Terminal fields were densest in the lateral and ventro-lateral periaqueductal gray (PAG), lateral parabrachial nucleus (LPB), caudal pressor area,and lamina I of the spinal trigeminal nucleus and all levels of the spinal cord. We thenlabeled cell types in the PAG, LPB, medulla, and spinal cord to better define the specifictargets of LJA5 boutons. LJA5 neurons send the only known inhibitory descending pro-jection specifically to lamina I of the spinal cord, which transmits afferent pain, tempera-ture, and itch information up to the brain. Using retrograde tracing, we found LJA5neurons receive inputs from sensory and stress areas such as somatosensory/insular cor-tex, preoptic area, paraventricular nucleus, dorsomedial nucleus and lateral hypothalamus,PAG, and LPB. This pattern of inputs and outputs suggest LJA5 neurons are uniquelypositioned to be activated by sensation and stress, and in turn, inhibit pain and itch.
