QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Song, S. Articles by Geller, A. I. Search for Related Content PubMed PubMed Citation Articles by Song, S. Articles by Geller, A. I.

 Previous Article  |  Next Article 

The Journal of Neuroscience, June 1, 1998, 18(11):4119-4132

Modulation of Rat Rotational Behavior by Direct Gene Transfer of Constitutively Active Protein Kinase C into Nigrostriatal Neurons

Song Song¹, Yaming Wang¹, Sun-Yung Bak¹, Matthew J. During², John Bryan¹, Oliver Ashe¹, Donna B. Ullrey¹, Laura E. Trask¹, Frederick D. Grant¹, Karen L. O'Malley³, Heimo Riedel⁴, David S. Goldstein⁵, Kim A. Neve⁶, Gerald J. LaHoste⁷, John F. Marshall⁷, John W. Haycock⁸, Rachael L. Neve^{9, 10}, and Alfred I. Geller^{1, 10}

¹ Division of Endocrinology, Children's Hospital, Boston, Massachusetts 02115, ² Departments of Surgery and Medicine, Yale University School of Medicine, New Haven, Connecticut 06510, ³ Department of Anatomy and Neurobiology, Washington University School of Medicine, St. Louis, Missouri 63110, ⁴ Department of Biological Sciences, Wayne State University, Detroit, Michigan 48202, ⁵ Clinical Neuroscience Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, ⁶ Research Service, Veterans Affairs Medical Center, Portland, Oregon 97201, ⁷ Department of Psychobiology, University of California, Irvine, California 92689, ⁸ Department of Biochemistry, Louisiana State University Medical Center, New Orleans, Louisiana, 70119, ⁹ Molecular Neurogenetics Laboratory, McLean Hospital, Belmont, Massachusetts 02178, and ¹⁰ Program in Neuroscience, Harvard Medical School, Boston, Massachusetts 02115

The modulation of motor behavior by protein kinase C (PKC) signaling pathways in nigrostriatal neurons was examined by using a genetic intervention approach. Herpes simplex virus type 1 (HSV-1) vectors that encode a catalytic domain of rat PKCII (Pkc) were developed. Pkc exhibited a constitutively active protein kinase activity with a substrate specificity similar to that of rat brain PKC. As demonstrated in cultured sympathetic neurons, Pkc caused a long-lasting, activation-dependent increase in neurotransmitter release. In the rat brain, microinjection of HSV-1 vectors that contain the tyrosine hydroxylase promoter targeted expression to dopaminergic nigrostriatal neurons. Expression of pkc in a small percentage of nigrostriatal neurons (~0.1-2%) was sufficient to produce a long-term (1 month) change in apomorphine-induced rotational behavior. Nigrostriatal neurons were the only catecholaminergic neurons that contained Pkc, and the amount of rotational behavior was correlated with the number of affected nigrostriatal neurons. The change in apomorphine-induced rotational behavior was blocked by a dopamine receptor antagonist (fluphenazine). D₂-like dopamine receptor density was increased in those regions of the striatum innervated by the affected nigrostriatal neurons. Therefore, this strategy enabled the demonstration that a PKC pathway or PKC pathways in nigrostriatal neurons modulate apomorphine-induced rotational behavior, and altered dopaminergic transmission from nigrostriatal neurons appears to be the affected neuronal physiology responsible for the change in rotational behavior.

Key words: genetic intervention; herpes simplex virus type 1 vectors; protein kinase C; nigrostriatal neurons; motor behavior; basal ganglia

---

Copyright © 1998 Society for Neuroscience  0270-6474/98/18114119-14$05.00/0

This article has been cited by other articles:

				G.-r. Zhang, X. Wang, L. Kong, X.-g. Lu, B. Lee, M. Liu, M. Sun, C. Franklin, R. G. Cook, and A. I. Geller Genetic Enhancement of Visual Learning by Activation of Protein Kinase C Pathways in Small Groups of Rat Cortical Neurons J. Neurosci., September 14, 2005; 25(37): 8468 - 8481. [Abstract] [Full Text] [PDF]

				Y. Wang, S. M. Camp, M. Niwano, X. Shen, J. C. Bakowska, X. O. Breakefield, and P. D. Allen Herpes Simplex Virus Type 1/Adeno-Associated Virus rep+ Hybrid Amplicon Vector Improves the Stability of Transgene Expression in Human Cells by Site-Specific Integration J. Virol., June 14, 2002; 76(14): 7150 - 7162. [Abstract] [Full Text] [PDF]

				M. S. Clark, T. J. Sexton, M. McClain, D. Root, R. Kohen, and J. F. Neumaier Overexpression of 5-HT1B Receptor in Dorsal Raphe Nucleus Using Herpes Simplex Virus Gene Transfer Increases Anxiety Behavior after Inescapable Stress J. Neurosci., June 1, 2002; 22(11): 4550 - 4562. [Abstract] [Full Text] [PDF]

				B. H. White, T. R. Cummins, D. H. Wolf, S. G. Waxman, D. S. Russell, and L. K. Kaczmarek HSV-1 Helper Virus 5dl1.2 Suppresses Sodium Currents in Amplicon-Transduced Neurons J Neurophysiol, April 1, 2002; 87(4): 2149 - 2157. [Abstract] [Full Text] [PDF]

				S. A. Josselyn, C. Shi, W. A. Carlezon Jr, R. L. Neve, E. J. Nestler, and M. Davis Long-Term Memory Is Facilitated by cAMP Response Element-Binding Protein Overexpression in the Amygdala J. Neurosci., April 1, 2001; 21(7): 2404 - 2412. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help