Synapses represent the basic unit of neuronal communications and are composed of paired pre- and post-synaptic terminals. Most of the excitatory synapses reside on dendritic spines, a type of dendritic protrusion that hosts neurotransmitter receptors and other postsynaptic specializations. Synapses are plastic and undergo short- and long-term modifications during developmental refinement of neuronal circuitry, as well as during learning and memory. Synaptic modifications involve both pre- and post-synaptic changes. At the postsynaptic site, directed trafficking of neurotransmitter receptors to and from the membrane surface is believed to be a key event underlying long-term potentiation (LTP) and depression (LTD), respectively. In addition, dendritic spines undergo rapid changes in their morphology in association with the plasticity. The underlying cellular mechanisms that control and regulate these rapid changes in postsynaptic receptors and spine structures remain to be fully elucidated. In this proposed project, we plan to investigate the cytoskeletal mechanisms that regulate postsynaptic dynamics and plasticity. We hypothesize that the actin eytoskeleton controls spine dynamics and receptor trafficking at the postsynaptic site and MTs contribute to spine development. We will take advantage of our imaging expertise and experience in studying cytoskeletal dynamics in cultured neurons and organotypic slices to understand the cytoskeletal regulation of postsynaptic structures and functions.
Three specific aims are proposed: (1) Cytoskeletal regulation of spine plasticity (2) ADF/cofilin in spine dynamics and receptor trafficking during plasticity (3) Local synthesis and degradation of actin-associated proteins during plasticity.

Public Health Relevance

Since many neural disorders are associated with alterations in synaptic connections, our study will not only provide a better understanding of the molecular and cellular mechanisms underlying synaptic plasticity, but also shed light on brain development and functions under both physiological and pathological conditions.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Program Projects (P01)
Project #
7P01HD023315-26
Application #
8733291
Study Section
Special Emphasis Panel (ZHD1-MCHG-B (DC))
Project Start
2013-07-03
Project End
2014-06-30
Budget Start
2013-07-03
Budget End
2014-06-30
Support Year
26
Fiscal Year
2013
Total Cost
$274,616
Indirect Cost
$25,722
Name
Rbhs-Robert Wood Johnson Medical School
Department
Type
DUNS #
078795875
City
Piscataway
State
NJ
Country
United States
Zip Code
08854
Lee, Hee Jae; Dreyfus, Cheryl; DiCicco-Bloom, Emanuel (2016) Valproic acid stimulates proliferation of glial precursors during cortical gliogenesis in developing rat. Dev Neurobiol 76:780-98
Mony, Tamanna Jahan; Lee, Jae Won; Dreyfus, Cheryl et al. (2016) Valproic Acid Exposure during Early Postnatal Gliogenesis Leads to Autistic-like Behaviors in Rats. Clin Psychopharmacol Neurosci 14:338-344
Huang, Yangyang; Dreyfus, Cheryl F (2016) The role of growth factors as a therapeutic approach to demyelinating disease. Exp Neurol 283:531-40
Das, Gitanjali; Yu, Qili; Hui, Ryan et al. (2016) EphA5 and EphA6: regulation of neuronal and spine morphology. Cell Biosci 6:48
Bowling, Heather; Bhattacharya, Aditi; Zhang, Guoan et al. (2016) BONLAC: A combinatorial proteomic technique to measure stimulus-induced translational profiles in brain slices. Neuropharmacology 100:76-89
Bowling, Heather; Bhattacharya, Aditi; Klann, Eric et al. (2016) Deconstructing brain-derived neurotrophic factor actions in adult brain circuits to bridge an existing informational gap in neuro-cell biology. Neural Regen Res 11:363-7
Sheleg, Michal; Yochum, Carrie L; Richardson, Jason R et al. (2015) Ephrin-A5 regulates inter-male aggression in mice. Behav Brain Res 286:300-7
Ma, Qian; Yang, Jianmin; Li, Thomas et al. (2015) Selective reduction of striatal mature BDNF without induction of proBDNF in the zQ175 mouse model of Huntington's disease. Neurobiol Dis 82:466-77
Anastasia, Agustin; Barker, Phillip A; Chao, Moses V et al. (2015) Detection of p75NTR Trimers: Implications for Receptor Stoichiometry and Activation. J Neurosci 35:11911-20
Yang, Jianmin; Harte-Hargrove, Lauren C; Siao, Chia-Jen et al. (2014) proBDNF negatively regulates neuronal remodeling, synaptic transmission, and synaptic plasticity in hippocampus. Cell Rep 7:796-806

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