Corticotropin-Releasing Factor Synapses within the Paraventricular Nucleus of the Hypothalamus

Abstract

Corticotropin-releasing factor (CRF) regulates the release of adrenocorticotropin (ACTH) from the anterior pituitary and these neurosecretory neurons reside in the paraventricular nucleus of the hypothalamus (PVN). In addition to its role as an ACTH secretogogue, exogenously administered CRF can act centrally to modify sympathetic outflow, alter various stress-induced behaviors and modulate its own secretion. Some of these effects might be mediated by CRF acting synaptically within the PVN as the nucleus is known to play a major role in integration of autonomic function. The current ultrastructural immunocytochemical study was designed to examine the range of synaptic relationships that CRF terminals make within the PVN. CRF-positive synapses were numerous, particularly in the periventricular zone. The majority of terminals formed axo-dendritic synapses and of these over 85% were the Gray’s type II (symmetrical) class. Axo-somatic terminals were also encountered and both parvicellular and magnocellular neurons were innervated. Once again most of the terminals were Gray’s type II. Although an innervation of unidentified structures was the most common, CRF synapses onto CRF neurons and dendrites were observed. All CRF/CRF interactions had symmetrical membrane specializations. These studies indicate that CRF could play a prominent role in the modulation of both parvicellular and magnocellular neurons within the paraventricular nucleus, including modulation of its own neurosecretory activity.

Gene expression analysis in the human hypothalamus in depression by laser microdissection and real-time PCR: the presence of multiple receptor imbalances

“…47 There are also CRF synapses on CRF neurons present in the rat PVN. 48 In our study, the increase of CRF was accompanied by an increase of CRFR1 expression in the PVN. This suggests a Abbreviations: AR, androgen receptor; AVP, vasopressin; AVPR1A, AVP receptor 1a; CRF, corticotropin-releasing factor; CRFR, CRF receptors; CREB, cAMP-response element-binding protein; ESR, estrogen receptor; GR, glucocorticoid receptor; HSP, heat shock protein; IL1b, interleukin 1-b; MR, mineralocorticoid receptor; OXT, oxytocin; PVN, paraventricular nucleus; SON, supraoptic nucleus; TNFa, tumor necrosis factor-a.…”

Bed Nucleus of the Stria Terminalis Subregions Differentially Regulate Hypothalamic–Pituitary–Adrenal Axis Activity: Implications for the Integration of Limbic Inputs

“…Additionally, glutamate (Glu) expressed in these anterior BST nuclei may also stimulate the HPA axis (Forray and Gysling, 2004). Thus, CRHexpressing central amygdalar neurons (Champagne et al, 1998) may activate the HPA axis by connecting with the dorsomedial/ fusiform BST nuclei (Prewitt and Herman, 1998) that express CRH/Glu to form an excitatory, bisynaptic CRH-CRH/Glu signal to the PVNmp (Paull and Gibbs, 1983;Silverman et al, 1989). Alternatively, the central nucleus of the amygdala may stimulate HPA activation (Van de Kar et al, 1991;Buller and Day, 2002) via GABA-GABA transsynaptic disinhibition (Cullinan et al, 1993) (Fig.…”

Increased expression level of corticotropin-releasing hormone in the amygdala and in the hypothalamus in rats exposed to chronic unpredictable mild stress

“…The main output neurons of the amygdala have been demonstrated to contain CRH peptide [35] . There are also synapses on CRH neurons in the rat PVN [36] . The above evidence combined with our findings suggests that the direct CRH neuron-involving connection between PVN and CeA plays an important role in the stress response.…”

“…Consequently, it regulates the activation of the HPA-axis via projections to the hypothalamus, which might underlie the increase of depressive behaviors and mood alterations. Some reports have indicated that neurons in CeA have direct projections to many areas in brain, including PVN in the hypothalamus [34][35][36][37] . Transmitter release from the amygdala onto PVN has been identified by Gray [35] .…”