The aim of this proposal is to study the developmental regulation of dendritic spine plasticity and the role of experience in modifying synaptic connections in postnatal life. Using an in vivo transcranial two-photon imaging technique, changes of individual dendritic spines will be followed over extended periods of time in different cell types and in diverse cortical regions. We will determine how and to what degree sensory experience and learning modulate dendritic spine plasticity in the developing and adult cortex. Furthermore, we will investigate whether experience-dependent spine plasticity is compromised in mouse models of Fragile X syndrome and Rett syndrome and if so, whether drug treatment can restore experience-dependent spine plasticity in mutant mice. Together, these studies will provide fundamental insights into how experience and genetic factors shape neural circuits at different stages of life and suggest new strategies for the treatment of mental retardation.

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The aim of this proposal is to study the developmental regulation of synaptic plasticity and the roles of sensory experience and motor learning in modifying neuronal connectivity in postnatal life. By taking advantage of in vivo two-photon microscopy, we will determine changes in postsynaptic dendritic spines in response to novel sensory stimuli and skill learning in the living mouse cortex. We will also establish an important link between abnormal dendritic spine dynamics and aberrant circuit formation in mouse models of mental retardation. These studies will reveal how sensory inputs and learning shape neuronal connectivity in the cerebral cortex at different stages of an animal's life and suggest novel strategies for the treatment of mental retardation.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Talley, Edmund M
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New York University
Schools of Medicine
New York
United States
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Lai, Baoling; Li, Miao; Hu, Wanling et al. (2018) The Phosphodiesterase 9 Inhibitor PF-04449613 Promotes Dendritic Spine Formation and Performance Improvement after Motor Learning. Dev Neurobiol 78:859-872
Lai, Cora Sau Wan; Adler, Avital; Gan, Wen-Biao (2018) Fear extinction reverses dendritic spine formation induced by fear conditioning in the mouse auditory cortex. Proc Natl Acad Sci U S A 115:9306-9311
Zhou, Yanmei; Lai, Baoling; Gan, Wen-Biao (2017) Monocular deprivation induces dendritic spine elimination in the developing mouse visual cortex. Sci Rep 7:4977
Cichon, Joseph; Blanck, Thomas J J; Gan, Wen-Biao et al. (2017) Activation of cortical somatostatin interneurons prevents the development of neuropathic pain. Nat Neurosci 20:1122-1132
Bai, Yang; Li, Miao; Zhou, Yanmei et al. (2017) Abnormal dendritic calcium activity and synaptic depotentiation occur early in a mouse model of Alzheimer's disease. Mol Neurodegener 12:86
Li, Wei; Ma, Lei; Yang, Guang et al. (2017) REM sleep selectively prunes and maintains new synapses in development and learning. Nat Neurosci 20:427-437
Cichon, Joseph; Gan, Wen-Biao (2015) Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature 520:180-5
Magrané, Jordi; Cortez, Czrina; Gan, Wen-Biao et al. (2014) Abnormal mitochondrial transport and morphology are common pathological denominators in SOD1 and TDP43 ALS mouse models. Hum Mol Genet 23:1413-24
Yang, Guang; Lai, Cora Sau Wan; Cichon, Joseph et al. (2014) Sleep promotes branch-specific formation of dendritic spines after learning. Science 344:1173-8
Marvin, Jonathan S; Borghuis, Bart G; Tian, Lin et al. (2013) An optimized fluorescent probe for visualizing glutamate neurotransmission. Nat Methods 10:162-70

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