Abstract
BACKGROUND: The paraventricular nucleus of the hypothalamus (PVN) has emerged as one of the most important autonomic control centers in the brain, with neurons playing essential roles in controlling stress, metabolism, growth, reproduction, immune and other more traditional autonomic functions (gastrointestinal, renal and cardiovascular). OBJECTIVES: Traditionally the PVN was viewed as a nucleus in which afferent inputs from other regions were faithfully translated into changes in single specific outputs, whether neuroendocrine or autonomic. Here we present data which suggest that the PVN plays significant and essential roles in integrating multiple sources of afferent input and sculpting an integrated autonomic output by concurrently modifying the excitability of multiple output pathways. In addition, we highlight recent work that suggests that dysfunction of such intranuclear integrative circuitry contributes to the pathology of conditions such as hypertension and congestive heart failure. CONCLUSIONS: This review highlights data showing that individual afferent inputs (subfornical organ), signaling molecules (orexins, adiponectin), and interneurons (glutamate/GABA), all have the potential to influence (and thus coordinate) multiple PVN output pathways. We also highlight recent studies showing that modifications in this integrated circuitry may play significant roles in the pathology of diseases such as congestive heart failure and hypertension.