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 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.