Activation of Corticotropin-Releasing Factor Receptor 2 in Lateral Septum Negatively Regulates Maternal Defense

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 mu g), urocortin (Ucn) 1 (0.2 mu g), and Ucn 3 (0.25 mu g) all significantly impaired maternal defense behavior. However, LS injections of CRF receptor 2 antagonist astressin-2B, but not a CRF receptor I 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.