Afferent connections of the dorsal premammillary nucleus

The dorsal premammillary nucleus (PMd) is thought to play a critical role for the expression of fear responses to environmental threats. We have reported previously that during an encounter with a predator the PMd presents an impressive increase in Fos levels and cell body-specific chemical lesions therein virtually eliminate the expression of escape and freezing responses. In the present study, we carried out a systematic analysis of PMd afferent connections combining anterograde and retrograde tracing methods in the rat. We show that the nucleus receives inputs from several widely distributed areas in the forebrain and, to a much lesser extent, from the brainstem as well. From this information, it seems that the major telencephalic source of input to the PMd is the interfascicular nucleus of the bed nuclei of the stria terminalis. In addition, substantial telencephalic inputs to the nucleus seem to arise from the infralimbic and prelimbic areas, and the lateral septal nucleus. In the diencephalon, massive inputs to the PMd arise from the anterior hypothalamic nucleus, specific parts of the perifornical region, the retinoceptive region of the lateral hypothalamic area, and the anterior and dorsomedial parts of the ventromedial hypothalamic nucleus. In contrast, the ventral tegmental nucleus seems to be the only brainstem site that provides substantial inputs to the PMd. Overall, the present analysis helps to delineate prosencephalic circuits seemingly critical for the organization of innate fear responses to environmental threats, where the PMd presents a major associative role. Furthermore, by means of massive inputs from the ventral tegmental nucleus, the PMd is in a position to integrate information from a neural system involved in spatial working memory, which may be of particular relevance for an effect of attentional mechanisms on the selection of appropriate escape strategies.