To help understand and mitigate human aggression, it is critical to develop appropriate animal models to understand all the different forms of aggression. Maternal aggression is a fierce aggression exhibited towards intruders by lactating female rodents when they are protecting their pups, that may share similarities with other short-lived, but fierce forms of human aggression. The goal of this proposed research, submitted by a new investigator, is to examine the neural basis of maternal aggression in mice. During lactation, decreases in corticotropin releasing hormone (CRH) neurotransmission have been linked to decreases in fear and anxiety. Because maternal aggression is high when fear and anxiety are low, it is possible that decreases in fear are necessary for a dam to be able to attack a normally fear evoking stimulus. Despite a possible link to maternal aggression, no work has systematically examined whether, or how, CRH plays a role in the control of this important social behavior. The studies proposed here test the hypothesis that regulation of CRH during lactation plays a necessary role in switching on maternal aggression. Consistent with this hypothesis we have collected evidence that intracerebroventricular (icv) injections of CRH inhibit maternal aggression and that decreases in endogenous CRH due to developmental intervention increase levels of maternal aggression. The three studies of this proposal will extend these preliminary findings and use multiple approaches to investigate further the role of CRH in maternal aggression. 1) Conduct icv injections of CRH, and a related peptide, urocortin III, and two CRH receptor antagonists to the lateral ventricle to determine the effect on maternal aggression. 2) Examine whether and where levels of CRH mRNA are decreased in mice that exhibit increased levels of maternal aggression due to a developmental intervention. 3) Examine levels of maternal aggression in mice that are missing either the CRH receptor 1 gene, or the CRH receptor 2 gene relative to control mice. Each study will also use indirect markers for neuronal activity, cFOS and FosB, to identify brain regions where CRH may be interacting with maternal aggression circuitry. Many studies have focused on male aggression, but far less is known about the neural basis of female aggression and preliminary results indicate that CRH has the opposite effect on male and maternal aggression. Basic research into sex differences in aggression, then, is important to understanding the biological underpinnings of sex and gender differences in social behavior, health, and disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
1R01MH066086-01A1
Application #
6681063
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Project Start
2003-07-01
Project End
2007-05-31
Budget Start
2003-07-01
Budget End
2004-05-31
Support Year
1
Fiscal Year
2003
Total Cost
$227,378
Indirect Cost
Name
University of Wisconsin Madison
Department
Zoology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
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Hasen, Nina S; Gammie, Stephen C (2011) Trpc2-deficient lactating mice exhibit altered brain and behavioral responses to bedding stimuli. Behav Brain Res 217:347-53
Lee, Grace; Gammie, Stephen C (2010) GABAA receptor signaling in caudal periaqueductal gray regulates maternal aggression and maternal care in mice. Behav Brain Res 213:230-7
D'Anna, Kimberly L; Gammie, Stephen C (2009) Activation of corticotropin-releasing factor receptor 2 in lateral septum negatively regulates maternal defense. Behav Neurosci 123:356-68
Gammie, S C; D'Anna, K L; Gerstein, H et al. (2009) Neurotensin inversely modulates maternal aggression. Neuroscience 158:1215-23
Hasen, N S; Gammie, S C (2009) Trpc2 gene impacts on maternal aggression, accessory olfactory bulb anatomy and brain activity. Genes Brain Behav 8:639-49
Lee, Grace; Gammie, Stephen C (2009) GABA(A) receptor signaling in the lateral septum regulates maternal aggression in mice. Behav Neurosci 123:1169-77
Gammie, Stephen C; Edelmann, Michelle N; Mandel-Brehm, Caleigh et al. (2008) Altered dopamine signaling in naturally occurring maternal neglect. PLoS One 3:e1974
D'Anna, Kimberly L; Stevenson, Sharon A; Gammie, Stephen C (2008) Maternal profiling of corticotropin-releasing factor receptor 2 deficient mice in association with restraint stress. Brain Res 1241:110-21
Gammie, S C; Seasholtz, A F; Stevenson, S A (2008) Deletion of corticotropin-releasing factor binding protein selectively impairs maternal, but not intermale aggression. Neuroscience 157:502-12

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