Activation of corticotropin-releasing factor receptor 2 in lateral septum negatively regulates maternal defense.

Abstract

Maternal defense (also known as maternal aggression) is impaired by corticotropin-releasing factor-(CRF) related peptides, but where these peptides inhibit defense is unknown. Lateral septum (LS) gates reactivity to stressors, contains receptors to CRF-related peptides, and during lactation shows a decreased response to CRF, suggesting LS is a key site for regulating maternal aggression. In this study, the authors examined the effects of CRF-related peptides in LS on maternal defense. LS injections of CRF (0.2 microg), urocortin (Ucn) 1 (0.2 microg), and Ucn 3 (0.25 microg) all significantly impaired maternal defense behavior. However, LS injections of CRF receptor 2 antagonist astressin-2B, but not a CRF receptor 1 antagonist, reversed the inhibitory effects of both septal CRF and Ucn 3. After intra-LS injection of peptides, c-Fos immunoreactivity was increased in ventromedial hypothalamus, lateral hypothalamus, and parabrachial nucleus, identifying these brain regions as possible downstream mediators of altered LS activity. Together, these findings indicate that CRF-related peptides similarly modulate maternal defense via CRF receptor 2, and that LS is a critical site for the negative regulation of maternal defense behavior.

Brain CRF-binding protein modulates aspects of maternal behavior under stressful conditions and supports a hypo-anxious state in lactating rats

“…Activation of CRF-R postpartum impairs the expression of maternal behavior thereby leading to maternal neglect (D'Anna and Gammie, 2009;Gammie et al, 2004;Klampfl et al, 2014Klampfl et al, , 2016Klampfl et al, 2013;Pedersen et al, 1991). Hence, hypoactivation of CRF-R during this sensitive period is an indispensable prerequisite for the appearance of appropriate maternal behavior.…”

“…Given that the CRF-BP is up-regulated by acute stressor exposure (Herringa et al, 2004;McClennen et al, 1998;Stinnett et al, 2015), we suggest that its release in the BNST is induced by exposure to the maternal defense test. This up-regulation is certainly important to protect the dam from potentially elevated levels of CRF, which are detrimental for the appearance of maternal behavior (D'Anna and Gammie, 2009;Gammie et al, 2004;Klampfl et al, 2014Klampfl et al, , 2016Klampfl et al, 2013;Pedersen et al, 1991). However, it needs to be mentioned that, as yet, no reliable measure for CRF peptide release is available and, therefore, we can only speculate about the intra-BNST release of CRF during the maternal defense test.…”

The role of maternal care in shaping CNS function

“…It has been postulated that low CRH receptor activity is needed for the expression of typical maternal behaviour. Initial studies revealed that CRH decreased maternal care and increased infanticide in an induced virgin rodent model of maternal care (Pedersen et al, 1991), and intracerebroventicular (icv) CRH also inhibits maternal aggression in mice (D'Anna and Gammie, 2009; Gammie et al, 2004; Gammie et al, 2008). The behavioural differences in the maternal care of rat and mouse strains bred for differing levels of anxiety (high anxiety behaviour/low anxiety behaviour, HAB/LAB) has been associated with differences in central CRH and AVP (Bosch et al, 2006; Kessler et al, 2011; Klampfl et al, 2013).…”

Urocortin 3 Modulates Social Discrimination Abilities via Corticotropin-Releasing Hormone Receptor Type 2

“…The site-specific injection of OT receptor agonists or antagonists has demonstrated a key role of the OT receptor in the MeA for social recognition (Ferguson et al, 2001). Nevertheless, it has been demonstrated that UCN1 and UCN3 modulate maternal behavior via CRH-R2 in the lateral septum D'Anna and Gammie, 2009), and accordingly, CRH-R2 knock-out mice exhibit impaired maternal defense of their offspring . Along these lines, UCN2 increases spontaneous parental behavior in prairie voles (Samuel et al, 2008).…”