How are basic mammalian behaviors such as sexual behavior and aggression regulated? Signaling pathways by hormones in neurons and glia, result in behavioral output. We are interested in understanding how signaling by small molecules such as estrogen in cells can coordinate behavior in the whole animal. We use estrogen regulation of social behaviors in rodents as a model system to understand this phenomenon.
Estrogens signal in two major mechanistic ways: a) classical genomic signaling resulting in regulation of genes (Figure 1) and b) rapid, cell membrane-initiated signaling leading to kinase activation and calcium influx (Figure 2). The latter mode of signaling is called the non-genomic mode of signaling to distinguish it from genomic signaling. What is the role of non-genomic signaling pathways in behavior? How do non-genomic, unconventional modes of signaling in cells integrate with classical modes of estrogen signaling? Using the mouse as a model, we attempt to understand the physiological significance of such integration in male aggressive behavior and neuronal morphology such as dendritic spines in behaviorally relevant areas (Figure 3). Techniques in this project include culturing primary neurons and cell lines, signaling assays, immunocytochemistry, western blotting, dendrite analysis and behavioral analysis.
Another hormone of clinical significance, whose action in the brain is poorly understood, is thyroid hormone. Currently, we use mouse models with either receptor loss or abnormal levels of thyroid hormones to probe the involvement of thyroid hormone in anxiety related syndromes using both mice behavior, spine analysis and gene expression assays.
Figure 1: The genomic mode of estrogen signaling. Estrogen (shown here as black triangles) diffuses into cells, binds the estrogen receptor (ER). The ER in the cell binds the estrogen response element (ERE) present in the promoter of target genes, thus regulating transcription. The ER is, hence, a ligand-dependent transcription factor.
Figure 2: The non-genomic mode of estrogen signaling. Estrogen (shown here as a black triangle) binds an unknown membrane ER (mER) and activates kinase and calcium flux within cells rapidly. The precise molecular mechanisms are unknown.
The focus of our laboratory
We explore the signaling pathways that are activated by a putative mER, in addition to the possible coupling mechanisms that link non-genomic signaling to genomic transcription. How these integrated signaling mechanisms play a role in behavior and the regulation of dendritic spines (both of which are independently influenced by estrogen) is also a focus of the laboratory.
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Cell and Molecular Biology, 2000 Percival Stern Hall, New Orleans, LA 70118 504-865-5546 firstname.lastname@example.org