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. ? ? ?
| Dunlap, Kent D; Jashari, Denisa; Pappas, Kristina M (2011) Glucocorticoid receptor blockade inhibits brain cell addition and aggressive signaling in electric fish, Apteronotus leptorhynchus. Horm Behav 60:275-83 |
| Dunlap, Kent D; McCarthy, Elizabeth A; Jashari, Denisa (2008) Electrocommunication signals alone are sufficient to increase neurogenesis in the brain of adult electric fish, Apteronotus leptorhynchus. Dev Neurobiol 68:1420-8 |
