Altered Hippocampal Neurogenesis and Amygdalar Neuronal Activity in Adult Mice with Repeated Experience of Aggression

Abstract

Repeated experience of winning in a social conflict setting elevates levels of aggression and may lead to violent behavioral patterns. Here, we use a paradigm of repeated aggression and fighting deprivation to examine changes in behavior, neurogenesis, and neuronal activity in mice with positive fighting experience. We show that for males, repeated positive fighting experience induces persistent demonstration of aggression and stereotypic behaviors in daily agonistic interactions, enhances aggressive motivation, and elevates levels of anxiety. When winning males are deprived of opportunities to engage in further fights, they demonstrate increased levels of aggressiveness. Positive fighting experience results in increased levels of progenitor cell proliferation and production of young neurons in the hippocampus. This increase is not diminished after a fighting deprivation period. Furthermore, repeated winning experience decreases the number of activated (c-fos-positive) cells in the basolateral amygdala and increases the number of activated cells in the hippocampus; a subsequent no-fight period restores the number of c-fos-positive cells. Our results indicate that extended positive fighting experience in a social conflict heightens aggression, increases proliferation of neuronal progenitors and production of young neurons in the hippocampus, and decreases neuronal activity in the amygdala; these changes can be modified by depriving the winners of the opportunity for further fights.

Developmental alterations in Huntington's disease neural cells and pharmacological rescue in cells and mice

“…Cells were then labeled with primary antibodies Tuj 1:1,000 (Sigma T8660) 56 , DARPP32 1:400 (Cell Signaling 19A3) 55 , Ki-67 1:400 (EMD MAB4190MI) 57 , GFAP 1:1,000 (DAKO Z0334) 58,59 , Map2ab 1:500 (Sigma M1406) 60 , myosin 1:20 (Developmental Studies Hybridoma Bank D7F2) 61 , Iba1 1:500 (Wako 019-19741) 62 , Sox17 1:500 (R&D AF1924) 63 , FoxA2 1:500 (Abnova H00003170-M01) 64 , O4 1:50 (StemCell 01416) 65 , nestin (EMD Millipore ABD69, 1:5,000) 66 , DCX (Aves Labs DCX, 1:1,000) 67 or PDGFR 1:500 (Santa Cruz SC-338) 68 for 60 min at room temperature or overnight at 4 °C, and then with the appropriate fluorescently tagged secondary antibodies (1:500; Life Technologies A-21202, A-31571, A-11005, A-21206, A-21207, A-31573) for 60 min at room temperature. Hoechst dye was used to label nuclei.…”

Social instigation and repeated aggressive confrontations in male Swiss mice: analysis of plasma corticosterone, CRF and BDNF levels in limbic brain areas

“…50 In agreement with our neuroendocrinal results, male mice exposed to a paradigm of repeated experience of winning in a social conflict have been demonstrated to present increased levels of anxiety in the elevated plus-maze test. 26 Increases in plasma glucocorticoids during a confrontation have been suggested to facilitate behaviors that are predominant for the animal in that specific context. 51 Indeed, brain mineralocorticoid receptor blockade during the first aggressive encounter inhibits subsequent propensity for violence in rats.…”

“…CRF was measured in the hippocampus and hypothalamus, areas previously related to aggression and behavioral and physiological responses to stress. 26,27 BDNF was measured in the PFC and hippocampus, brain regions associated with behavioral planning and affective behaviors. 28 The primary role of CRF is to activate the hypothalamic-pituitary-adrenal (HPA) axis by acting on receptors in the pituitary and promoting the release of adrenocorticotropic hormone (ACTH) into the portal blood system.…”

Adult mammalian neurogenesis and motivated behaviors

“…In male mice, positive fighting experiences (aka winning) were found to increase adult neurogenesis in the hippocampus. In particular, 4 mouse species (wildtype C57BL/6J, wild type C57BL/Icg, transgenic Nestin-GFP homozygous mice, and transgenic Nestin-GFP heterozygous mice) displayed an increased level of hippocampal cell proliferation after chronic positive fighting experiences in comparison to control mice (no fighting experience) (Smagin et al 2015). Because aggression is associated with heightened levels of testosterone, one could speculate that testosterone underlies the changes in adult neurogenesis observed due to dominance (Book et al 2001).…”