Investigations into the molecular targets of drugs of abuse and their associated intracellular signaling pathways by this Program Project Grant have yielded a wealth of information regarding the cellular perturbations associated with these drugs. The combined studies outlined in Project 1-3 will extend upon this existing knowledge with rigorous cell biological, molecular, biochemical, behavioral and electrophysiological studies of striatal neurons following drug treatment. The Scientific Core will be devoted to facilitating the experiments proposed in Projects 1-3. The centralized responsibility for the performance of routine tasks, such as the maintenance of mouse colonies and the supply of common reagents, provides for an efficient, flexible and cost-effective means to ensure an adequate supply of required materials for all Projects.The major aims of the Scientific Core will be:
Aim I. The characterization and maintenance of transgenic mouse colonies;
Aim II. The production of key reagents, including polyclonal antibodies, phosphorylation state-specific antibodies, the design and execution of yeast two-hybrid screens, and the production of AAV viruses;
Aim III. The analysis of dendritic spines. All Scientific Core Aims will be conducted in close, ongoing consultation with the staff from Projects 1-3, such that services are delivered as required. The mice produced by the Scientific Core will be essential for many of the studies proposed in Projects 1-3, due to a heavy reliance on genetically modified animals. Production by a centralized Core will ensure optimal animal production and use. The biochemical and immunological reagents generated by the Scientific Core will also be necessary for Projects. The analysis of dendritic spines will be essential for Project 1, and will also help Projects 2 and 3 to carry out their proposed studies of dendritic spine morphology.
The proposed studies in this Program Project Grant will have the potential to provide greater insights into the causes of drug dependence as well as to help identify possible novel targets for pharmacological intervention. The Scientific Core will support this effort through facilitation of the three Projects in the Program Project Grant.
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|Seo, J-S; Zhong, P; Liu, A et al. (2018) Elevation of p11 in lateral habenula mediates depression-like behavior. Mol Psychiatry 23:1113-1119|
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|Chang, Audrey N; Gao, Ning; Liu, Zhenan et al. (2018) The dominant protein phosphatase PP1c isoform in smooth muscle cells, PP1c?, is essential for smooth muscle contraction. J Biol Chem 293:16677-16686|
|Andrade, Erika C; Musante, Veronica; Horiuchi, Atsuko et al. (2017) ARPP-16 Is a Striatal-Enriched Inhibitor of Protein Phosphatase 2A Regulated by Microtubule-Associated Serine/Threonine Kinase 3 (Mast 3 Kinase). J Neurosci 37:2709-2722|
|Musante, Veronica; Li, Lu; Kanyo, Jean et al. (2017) Reciprocal regulation of ARPP-16 by PKA and MAST3 kinases provides a cAMP-regulated switch in protein phosphatase 2A inhibition. Elife 6:|
|Milosevic, Ana; Liebmann, Thomas; Knudsen, Margarete et al. (2017) Cell- and region-specific expression of depression-related protein p11 (S100a10) in the brain. J Comp Neurol 525:955-975|
|Ceglia, Ilaria; Lee, Ko-Woon; Cahill, Michael E et al. (2017) WAVE1 in neurons expressing the D1 dopamine receptor regulates cellular and behavioral actions of cocaine. Proc Natl Acad Sci U S A 114:1395-1400|
|Seo, J-S; Wei, J; Qin, L et al. (2017) Cellular and molecular basis for stress-induced depression. Mol Psychiatry 22:1440-1447|
|Nishi, Akinori; Matamales, Miriam; Musante, Veronica et al. (2017) Glutamate Counteracts Dopamine/PKA Signaling via Dephosphorylation of DARPP-32 Ser-97 and Alteration of Its Cytonuclear Distribution. J Biol Chem 292:1462-1476|
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