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

Smagin DA, Park JH, Michurina TV, Peunova N, Glass Z, Sayed K, Bondar NP, Kovalenko IN, Kudryavtseva NN, Enikolopov G - Front Neurosci (2015)

Bottom Line: Positive fighting experience results in increased levels of progenitor cell proliferation and production of young neurons in the hippocampus.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences Novosibirsk, Russia ; Department of Nano-, Bio-, Information Technology and Cognitive Science, Moscow Institute of Physics and Technology Moscow, Russia ; Cold Spring Harbor Laboratory, Cold Spring Harbor NY, USA.

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.

No MeSH data available.


Related in: MedlinePlus

Subclasses of progenitor cells in the SGZ of the DG of Nestin-GFP male mice. Numbers of dividing GFP+BrdU+ progenitor cells (A), ANP cells (B), dividing ANP cells (C), QNP cells (D), dividing QNP cells (E), and Dcx+ young neurons (F). *P < 0.05, **P < 0.01; t-test.
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Figure 3: Subclasses of progenitor cells in the SGZ of the DG of Nestin-GFP male mice. Numbers of dividing GFP+BrdU+ progenitor cells (A), ANP cells (B), dividing ANP cells (C), QNP cells (D), dividing QNP cells (E), and Dcx+ young neurons (F). *P < 0.05, **P < 0.01; t-test.

Mentions: Incorporation of thymidine analogs, while marking cells undergoing DNA synthesis, does not distinguish between neuronal progenitors and other dividing cells types (e.g., oligodendrocyte progenitors, microglia, pericytes, or endothelial cells) or between different classes of neuronal progenitors (e.g., stem cells and their amplifying progeny). Therefore, we further analyzed mice of the reporter Nestin-GFP line in which various classes of neuronal progenitors can be distinguished from other classes of progenitors or other cell types based on the expression of the reporter, morphology, and additional markers (Mignone et al., 2004; Enikolopov et al., 2015). We analyzed the number of GFP-positive cells in the subgranular zone (SGZ) that were labeled with BrdU and found that the number of GFP+BrdU+ cells was increased, indicating that the increase in dividing cells was driven by neuronal progenitors. The majority of GFP+BrdU+ cells in adult mice of this reporter line corresponds to amplifying neural progenitors (ANP), whereas a smaller fraction corresponds to the quiescent neural stem cell population (QNP; Encinas et al., 2011b). These two cell types can be distinguished by their morphology (e.g., by the radial glia-like shape of quiescent stem cells) aided by marker expression (GFAP expression in the stem cells, but not in their amplifying progeny). We found an increase in the overall number of ANPs and in the number of BrdU-positive ANPs, but not in the number of QNPs or dividing QNPs (Figure 3). This suggests that prolonged winning experience in agonistic interactions does not change the number of the hippocampal stem cells, but increases the number of their rapidly dividing progeny.


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

Smagin DA, Park JH, Michurina TV, Peunova N, Glass Z, Sayed K, Bondar NP, Kovalenko IN, Kudryavtseva NN, Enikolopov G - Front Neurosci (2015)

Subclasses of progenitor cells in the SGZ of the DG of Nestin-GFP male mice. Numbers of dividing GFP+BrdU+ progenitor cells (A), ANP cells (B), dividing ANP cells (C), QNP cells (D), dividing QNP cells (E), and Dcx+ young neurons (F). *P < 0.05, **P < 0.01; t-test.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4664700&req=5

Figure 3: Subclasses of progenitor cells in the SGZ of the DG of Nestin-GFP male mice. Numbers of dividing GFP+BrdU+ progenitor cells (A), ANP cells (B), dividing ANP cells (C), QNP cells (D), dividing QNP cells (E), and Dcx+ young neurons (F). *P < 0.05, **P < 0.01; t-test.
Mentions: Incorporation of thymidine analogs, while marking cells undergoing DNA synthesis, does not distinguish between neuronal progenitors and other dividing cells types (e.g., oligodendrocyte progenitors, microglia, pericytes, or endothelial cells) or between different classes of neuronal progenitors (e.g., stem cells and their amplifying progeny). Therefore, we further analyzed mice of the reporter Nestin-GFP line in which various classes of neuronal progenitors can be distinguished from other classes of progenitors or other cell types based on the expression of the reporter, morphology, and additional markers (Mignone et al., 2004; Enikolopov et al., 2015). We analyzed the number of GFP-positive cells in the subgranular zone (SGZ) that were labeled with BrdU and found that the number of GFP+BrdU+ cells was increased, indicating that the increase in dividing cells was driven by neuronal progenitors. The majority of GFP+BrdU+ cells in adult mice of this reporter line corresponds to amplifying neural progenitors (ANP), whereas a smaller fraction corresponds to the quiescent neural stem cell population (QNP; Encinas et al., 2011b). These two cell types can be distinguished by their morphology (e.g., by the radial glia-like shape of quiescent stem cells) aided by marker expression (GFAP expression in the stem cells, but not in their amplifying progeny). We found an increase in the overall number of ANPs and in the number of BrdU-positive ANPs, but not in the number of QNPs or dividing QNPs (Figure 3). This suggests that prolonged winning experience in agonistic interactions does not change the number of the hippocampal stem cells, but increases the number of their rapidly dividing progeny.

Bottom Line: Positive fighting experience results in increased levels of progenitor cell proliferation and production of young neurons in the hippocampus.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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Cytology and Genetics, Siberian Branch of Russian Academy of Sciences Novosibirsk, Russia ; Department of Nano-, Bio-, Information Technology and Cognitive Science, Moscow Institute of Physics and Technology Moscow, Russia ; Cold Spring Harbor Laboratory, Cold Spring Harbor NY, USA.

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.

No MeSH data available.


Related in: MedlinePlus