Hypothalamic corticotropin-releasing factor neurons modulate behavior, endocrine, and autonomic stress responses via direct synaptic projections

Abstract

In response to stress, corticotropin-releasing factor (CRF) neurons located in the paraventricular nucleus of the hypothalamus (PVN) activate the hypothalamic–pituitary–adrenal (HPA) axis. Recently, PVN CRF neurons have been shown to also modulate stress-responsive behavior dynamically, via direct synaptic projections. In addition, a population of CRF receptor 1 (CRFR1) positive neurons were identified in the PVN that respond to local CRF release and project to local, rostral and caudal brain nuclei to influence stress responses. Both direct projections by CRF neurons and local activation of CRFR1+ neurons in the PVN allow CRF neurons that traditionally have been thought to be dedicated to controlling HPA axis activity to also modulate behavior, endocrine and autonomic features of the stress response acutely as a threat unfolds.