We are examining how group 1 metabotropic glutamate receptors modify neuronal function and synaptic plasticity. This scientific goal is relevant to drug addiction since genetic deletion of mGluRS prevents neurobehavioral actions of cocaine Including behavioral activation and cocaine sensitization (Chiamulera et al., 2001). Moreover, mGluRS antagonists block behavioral responses to cocaine in rodents (Herzig and Schmidt, 2004) and primates (Lee et al., 2005;Paquet and Smith, 2003). One of our central hypotheses is that actions of mGIuR that are criticai for addition are transduced through the acton of a regulated adaptor system, that includes constitutively expressed Homer proteins together with an Immediate eariy gene fomn of Homer (H1 a). Homer proteins bind the C-terminus of group 1 metabotropic glutamate receptors as well as proteins that are down stream of mGluR in its various signaling pathways, and by self multimerization Homer can assemble these proteins into signaling complexes. The actions of Homer on mGluR signaling are complex and remari^ably elegant;Homer can regulate pharmacology of the receptor (Ango et al., 2001), the amplitude of the output and ability of the mGluR to receive convergent signals from dopamine receptors (DR) and growth factors including TritB. These pathways appear important for an understanding of the role of mGluR in addiction since genetic deletion of Homer results in enhanced sensitivity of mice to the addictive properties of cocaine

National Institute of Health (NIH)
National Institute on Drug Abuse (NIDA)
Method to Extend Research in Time (MERIT) Award (R37)
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Special Emphasis Panel (NSS)
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Pollock, Jonathan D
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Johns Hopkins University
Schools of Medicine
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Datko, Michael C; Hu, Jia-Hua; Williams, Melanie et al. (2017) Behavioral and Neurochemical Phenotyping of Mice Incapable of Homer1a Induction. Front Behav Neurosci 11:208
Marton, Tanya M; Hussain Shuler, Marshall G; Worley, Paul F (2015) Homer 1a and mGluR5 phosphorylation in reward-sensitive metaplasticity: A hypothesis of neuronal selection and bidirectional synaptic plasticity. Brain Res 1628:17-28
Obara, Ilona; Goulding, Scott P; Hu, Jia-Hua et al. (2013) Nerve injury-induced changes in Homer/glutamate receptor signaling contribute to the development and maintenance of neuropathic pain. Pain 154:1932-45
Park, Joo Min; Hu, Jia-Hua; Milshteyn, Aleksandr et al. (2013) A prolyl-isomerase mediates dopamine-dependent plasticity and cocaine motor sensitization. Cell 154:637-50
Huang, Guo N (2012) T Cell Calcium Mobilization Study (Flow Cytometry). Bio Protoc 2:
Huang, Guo N (2012) Biotinylation of Cell Surface Proteins. Bio Protoc 2:
Zou, Jia; Zhou, Liang; Du, Xiao-Xia et al. (2011) Rheb1 is required for mTORC1 and myelination in postnatal brain development. Dev Cell 20:97-108
Hu, Jia-Hua; Park, Joo Min; Park, Sungjin et al. (2010) Homeostatic scaling requires group I mGluR activation mediated by Homer1a. Neuron 68:1128-42
Lee, Kyu Pil; Yuan, Joseph P; Zeng, Weizhong et al. (2009) Molecular determinants of fast Ca2+-dependent inactivation and gating of the Orai channels. Proc Natl Acad Sci U S A 106:14687-92
Yuan, Joseph P; Kim, Min Seuk; Zeng, Weizhong et al. (2009) TRPC channels as STIM1-regulated SOCs. Channels (Austin) 3:221-5

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