Connections between the central nucleus of the amygdala and the midbrain periaqueductal gray: Topography and reciprocity

Previous reports indicate that the midbrain periaqueductal gray and the central nucleus of the amygdala are interconnected but the organization of these projections has not been characterized. We have analyzed this reciprocal circuitry using anterograde and retrograde tracing methods and image analysis. Our findings reveal that innervation of periaqueductal gray from the central nucleus of the amygdala is extensive and discretely organized along the rostrocaudal axis of periaqueductal gray. In addition, the reciprocal projection from periaqueductal gray to the central nucleus of the amygdala is more extensive and more highly organized than previously suggested. Multiple or single discrete injections of wheatgerm agglutinin-horseradish peroxidase into several rostrocaudal levels of periaqueductal gray retrogradely labeled a substantial population of neurons, predominantly located in the medial division of the central nucleus of the amygdala. Tracer injections into the central nucleus revealed a high degree of spatial organization in the projection from this nucleus to periaqueductal gray. Two discrete longitudinally directed columns in dorsomedial and lateral/ventrolateral periaqueductal gray are heavily targeted by central amygdalar inputs throughout the rostral one-half to two-thirds of periaqueductal gray. Beginning at the level of dorsal raphe and continuing caudally, inputs from the central nucleus terminate more uniformly throughout the ventral half of periaqueductal gray. In addition, a substantial population of periaqueductal gray neurons were retrogradely labeled from the central nucleus of the amygdala; these were heterogeneously distributed along the rostrocaudal axis of periaqueductal gray, and included both raphe and non-raphe neurons. Thus, the present study demonstrates that periaqueductal gray receives heavy, highly organized projections from the central nucleus of the amygdala and, in turn, has reciprocal connections with the central nucleus. Previous studies have demonstrated that longitudinally organized columns of output neurons located in dorsomedial and lateral/ventrolateral periaqueductal gray project to the ventral medulla. Thus, there may be considerable overlap between the two longitudinally organized terminal input columns from the central nucleus of the amygdala and the two longitudinal columns of descending projection neurons from periaqueductal gray to the ventral medulla. The central nucleus of the amygdala has been implicated in a variety of emotional/cognitive functions ranging from fear and orienting responses, defensive and aversive reactions, associative conditioning, cardiovascular regulation, and antinociception. Many of these same functions are strongly represented in the periaqueductal gray. It is noteworthy that the present results demonstrate that lateral periaqueductal gray, a preeminent central trigger site for behavioral and autonomic components of the defense/aversion response, is heavily targeted by inputs from the central nucleus of the amygdala at all levels of periaqueductal gray.(ABSTRACT TRUNCATED AT 400 WORDS)