PI of the laboratory: Jean-Pierre Hornung
Gender difference in developing anxiety phenotype in the 5-HT1aR knock-out mice
Description of Project:
In mice lacking the serotonin receptor 1A (5-HT1aR), animals express an enhanced anxiety-like behavior in the open-field and novelty suppressed feeding tests. In parallel, there is a change in the connectivity with increased dendritic arborization in CA1 pyramidal neurons. These changes have been shown to be developmentally regulated during early postnatal maturation of the mouse brain. Using 5-HT1aR-KO mice with expression of GFP in a subpopulation of hippocampal pyramidal neurons, we have recently observed that there is a correlation between the severity of the anxious behavior and the amount of changes In dendritic arborization of hippocampal neurons. This correlation was strong in males and absent in females.
It raises the contribution of sexual hormones on the gender difference on specific natural or pathological behaviors. Growth of dendritic branches in hippocampal neurons is associated with the 5-HT1aR-KO phenotype, and this growth can be monitored and pharmacologically modulated in organotypic slices cultures of the hippocampus.
The project is articulated along two lines of experiments. In vitro, slices of hippocampus will be treated with or without estrogens, and the contribution of estrogen receptors stimulation on the regulation of dendritic growth of hippocampal neuron will be evaluated. In vivo, the anxiety like behavior will be compared in knock-out animals of both sex, as well as in castrated females and males receiving regular infusion of estrogen agonist.
In both cultured slices and live animals, GFP is expressed in hippocampal pyramidal neurons and the dendritic arborization of large samples of neurons will be analyzed using morphometric quantitative methods. It is hypothesized that estrogen circulating in female animals counteract the lack of 5-HT1aR activation in knock-out , and therefore reduces the impact of the serotonergic defect on the anxiety behavior.
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