Kent D. Dunlap - US grants

estrogen receptors; receptor expression; gene expression; estrogens; hormone regulation /control mechanism; fish electric organ; female; in situ hybridization; catfish; molecular cloning;

[unreadable] DESCRIPTION (provided by applicant): The central nervous system of mammals has a relatively limited ability to generate new neurons during adulthood. However, environmental and hormonal stimuli can increase rates of neurogenesis in certain brain regions, suggesting that such stimuli might be eventually used therapeutically to enhance the repair of damaged or diseased brain regions and restore behavioral function. The research proposed here is the first stage of a research program designed to understand how social stimuli and steroid treatment modify the rate of naturally occurring neurogenesis and how the resultant structural changes in the adult brain relate to behavioral plasticity. Electric fish are used for this research because the neural circuits controlling behavior are very well described, their behavior is known to respond to social and steroidal stimuli and their brain is known to have a high level of structural plasticity during adulthood. To test the hypothesis that social stimulation and glucocorticoid treatment simultaneously affect neurogenesis and social behavior, 1) adult fish will be housed separately and or in pairs [sic], or implanted with cortisol or empty capsule 2) electrocommunication behavior will be assayed by presentation of standard electrical stimuli, and 3) neuronal proliferation in the brain will be determined by examining the distribution of BrdU incorporation and a neural specific protein, Hu. To test the hypothesis that electrocommunication signals from another fish are sufficient to enhance adult neurogenesis, fish will be exposed to conditions in which they receive a) no social interaction, b) normal social interaction, c) social interaction through the electric modality alone or d) stimulation with non-social electrical stimuli, and the distribution of BrdU incorporation will be examined in brain regions within and outside of the electrocommunication system. These pilot studies will serve to identify specific stimuli and brain regions capable of induced neurogenesis in a model system that has great promise for clarifying links between environment, brain plasticity and behavioral function [unreadable] [unreadable]

[unreadable] DESCRIPTION (provided by applicant): The mammalian brain has a limited ability to generate new neurons during adulthood. However, environmental and hormonal stimuli can increase rates of neurogenesis in certain brain regions, suggesting that such stimuli might eventually be used therapeutically to enhance the repair of damaged or diseased brain regions and restore behavioral function. Electric fish have unusual promise as a model for the function and regulation adult-born brain cells because their neural circuits controlling certain behaviors are unusually simple and well described, and their brains show unusually high rates of cell proliferation. In pilot studies funded by NIMH (R03), the researchers used electric fish to establish links between the social environment, glucocorticoid hormones, brain plasticity and communication behavior. Specifically, they demonstrated that both pairing fish together and implanting fish with cortisol potentiated an electrocommunication behavior termed chirping and increased cell addition and radial glial fiber density in the brain region that controls chirping behavior. In this second stage of the research, the researchers ask four questions: 1) What is the phenotypic fate of socially-induced cells? After pairing fish together, they will co-label brains with antibodies to markers of cell addition (BrdU) and neuronal (Hu) and glial (GFAP, S100B) differentiation. 2) Do newborn cells become active during chirping behavior? The investigators will co-label with antibodies for markers of cell addition (BrdU) and an immediate early gene protein (c-fos) in the brains of fish soon after they are stimulated with chirp-eliciting stimuli. 3) Does cortisol play a causal role in socially-induced plasticity in brain and behavior? The researchers will treat fish simultaneously with social interaction and a glucocorticoid receptor blocker (RU486) and then assay for brain cell addition radial glial fibers density and chirping behavior. 4) What specific stimuli present in social interaction are most effective in causing brain and behavioral plasticity? The researchers will pair fish in stimulus environments that allow for differing degrees of communication and then determine whether brain plasticity is associated with the reception or production of electrocommunication signals. As an AREA grant, this research project would also significantly enhance the training of undergraduate researchers. These studies will help establish the phenotype, functionality, and regulation of adult-born brain cells in a model system that holds promise for determining how newborn cells modify neural circuits and behavior. In humans, social interaction improves the recovery from brain injury and slows the process of neurodegeneration. Animal studies indicate that part of this benefit of social interaction may occur through its positive effect on the formation of new neurons. This research seeks to identify specific features of social interaction that promote new neuron formation. [unreadable] [unreadable] [unreadable]