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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS047325-09
Application #
8311740
Study Section
Synapses, Cytoskeleton and Trafficking Study Section (SYN)
Program Officer
Mamounas, Laura
Project Start
2003-12-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
9
Fiscal Year
2012
Total Cost
$431,423
Indirect Cost
$176,143
Name
New York University
Department
Physiology
Type
Schools of Medicine
DUNS #
121911077
City
New York
State
NY
Country
United States
Zip Code
10016
Cichon, Joseph; Gan, Wen-Biao (2015) Branch-specific dendritic Ca(2+) spikes cause persistent synaptic plasticity. Nature 520:180-5
Magrane, 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
Sudarov, Anamaria; Gooden, Frank; Tseng, Debbie et al. (2013) Lis1 controls dynamics of neuronal filopodia and spines to impact synaptogenesis and social behaviour. EMBO Mol Med 5:591-607
Yang, Guang; Parkhurst, Christopher N; Hayes, Scott et al. (2013) Peripheral elevation of TNF-α leads to early synaptic abnormalities in the mouse somatosensory cortex in experimental autoimmune encephalomyelitis. Proc Natl Acad Sci U S A 110:10306-11
Liston, Conor; Cichon, Joseph M; Jeanneteau, Freddy et al. (2013) Circadian glucocorticoid oscillations promote learning-dependent synapse formation and maintenance. Nat Neurosci 16:698-705
Yang, Guang; Pan, Feng; Chang, Paul C et al. (2013) Transcranial two-photon imaging of synaptic structures in the cortex of awake head-restrained mice. Methods Mol Biol 1010:35-43
Parkhurst, Christopher N; Yang, Guang; Ninan, Ipe et al. (2013) Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor. Cell 155:1596-609
Chen, Qian; Cichon, Joseph; Wang, Wenting et al. (2012) Imaging neural activity using Thy1-GCaMP transgenic mice. Neuron 76:297-308

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