Deficits in learning and memory are prominent features of many mental disorders. Understanding molecular mechanisms responsible for learning and memory are key to the development of therapies to improve learning and memory in the treatment of mental illness. Recent studies lead to the exciting idea that newly generated neurons in the adult dentate gyrus (DG) of the hippocampus may play a role in neural plasticity including hippocampal-dependent memory formation. Adult neurogenesis occurs in the DG of the mammalian brains including adult human brain under physiological conditions and newly generated neurons functionally integrate to the DG. Many factors, including depression and other mental illness may adversely affect hippocampal adult neurogenesis. In contrast, treatment with anti-depressants and exercise, an effective means to treat depression, enhance adult neurogenesis in the DG. Consequently, elucidation of basic molecular mechanisms regulating adult hippocampal neurogenesis and generation of definitive evidence supporting a role for adult neurogenesis in hippocampal-dependent memory formation is a critical and timely issue for mental health research. Although many studies have assessed the role of adult neurogenesis in hippocampal-dependent learning and memory, the results have been inconsistent, making it still highly controversial whether adult neurogenesis contributes to hippocampus-dependent memory formation. This proposal will test the hypothesis that ERK5 signaling-mediated adult neurogenesis plays a critical role in some but not all forms of hippocampal- dependent learning and memory.

Public Health Relevance

Our proposed studies are likely to provide new insights concerning signal transduction mechanisms regulating adult neurogenesis, and may lead to new insights to the development of therapies to improve learning and memory in the treatment of mental illness.

National Institute of Health (NIH)
Research Project (R01)
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Neurobiology of Learning and Memory Study Section (LAM)
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Panchision, David M
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University of Washington
Public Health & Prev Medicine
Schools of Public Health
United States
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Wang, Wenbin; Pan, Yung-Wei; Zou, Junhui et al. (2014) Genetic activation of ERK5 MAP kinase enhances adult neurogenesis and extends hippocampus-dependent long-term memory. J Neurosci 34:2130-47
Li, Tan; Wang, Wenbin; Pan, Yung-Wei et al. (2013) A hydroxylated metabolite of flame-retardant PBDE-47 decreases the survival, proliferation, and neuronal differentiation of primary cultured adult neural stem cells and interferes with signaling of ERK5 MAP kinase and neurotrophin 3. Toxicol Sci 134:111-24
Pan, Yung-Wei; Storm, Daniel R; Xia, Zhengui (2013) Role of adult neurogenesis in hippocampus-dependent memory, contextual fear extinction and remote contextual memory: new insights from ERK5 MAP kinase. Neurobiol Learn Mem 105:81-92
Li, Tan; Pan, Yung-Wei; Wang, Wenbin et al. (2013) Targeted deletion of the ERK5 MAP kinase impairs neuronal differentiation, migration, and survival during adult neurogenesis in the olfactory bulb. PLoS One 8:e61948
Zou, Junhui; Storm, Daniel R; Xia, Zhengui (2013) Conditional deletion of ERK5 MAP kinase in the nervous system impairs pheromone information processing and pheromone-evoked behaviors. PLoS One 8:e76901
Wang, Wenbin; Pan, Yung-Wei; Wietecha, Tomasz et al. (2013) Extracellular signal-regulated kinase 5 (ERK5) mediates prolactin-stimulated adult neurogenesis in the subventricular zone and olfactory bulb. J Biol Chem 288:2623-31
Pan, Yung-Wei; Wang, Wenbin; Xia, Zhengui (2013) Assessment of adult neurogenesis in mice. Curr Protoc Toxicol Chapter 12:Unit12.20