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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 30, 2003, 23(17):6759-6767

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 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 Web of Science (29) Citing Articles via Google Scholar Google Scholar Articles by Yamamoto, M. Articles by Nakanishi, S. Search for Related Content PubMed PubMed Citation Articles by Yamamoto, M. Articles by Nakanishi, S.

 Previous Article  |  Next Article 

Reversible Suppression of Glutamatergic Neurotransmission of Cerebellar Granule Cells In Vivo by Genetically Manipulated Expression of Tetanus Neurotoxin Light Chain

Mutsuya Yamamoto,^1,2,3 Norio Wada,² Yasuji Kitabatake,³ Dai Watanabe,³ Masayuki Anzai,⁴ Minesuke Yokoyama,⁵ Yutaka Teranishi,⁵ and Shigetada Nakanishi^2,3

¹Mitsubishi Pharma Corporation, Discovery Technology Laboratory, Yokohama, 227-0033, Japan, ²Department of Molecular and System Biology, Kyoto University Graduate School of Biostudies, Kyoto, 606-8501, Japan, ³Department of Biological Sciences, Kyoto University Faculty of Medicine, Kyoto, 606-8501, Japan, ⁴GenCom Corporation, Machida, 194-8511, Japan, and ⁵Mitsubishi Kagaku Institute of Life Sciences, Machida, 194-8511, Japan

We developed a novel technique that allowed reversible suppression of glutamatergic neurotransmission in the cerebellar network. We generated two lines of transgenic mice termed Tet and TeNT mice and crossed the two transgenic lines to produce the Tet/TeNT double transgenic mice. In the Tet mice, the tetracycline-controlled reverse activator (rtTA) was expressed selectively in cerebellar granule cells by the promoter function of the GABA_A receptor 6 subunit gene. In the TeNT mice, the fusion gene of tetanus neurotoxin light chain (TeNT) and enhanced green fluorescent protein (EGFP) was designed to be induced by the interaction of doxycycline (DOX)-activated rtTA with the tetracycline-responsive promoter. The Tet/TeNT mice grew normally even after DOX treatment and exhibited a restricted DOX-dependent expression of TeNT in cerebellar granule cells. Along with this expression, TeNT proteolytically cleaved the synaptic vesicle protein VAMP2 (also termed synaptobrevin2) and reduced glutamate release from granule cells. Both cleavage of VAMP2/synaptobrevin2 and reduction of glutamate release were reversed by removal of DOX. Among the four genotypes generated by heterozygous crossing of Tet and TeNT mice, only Tet/TeNT mice showed DOX-dependent reversible motor impairments as analyzed with fixed bar and rota-rod tests. Reversible suppression of glutamatergic neurotransmission thus can be manipulated with spatiotemporal accuracy by DOX treatment and removal. These transgenic mice will serve as an animal model to study the cerebellar function in motor coordination and learning.

Key words: transgenic mouse; GABA_A receptor; tetanus neurotoxin; tetracycline-inducible system; cerebellum; granule cell; VAMP2; glutamatergic transmission

---

Received Apr. 23, 2003; revised Jun. 3, 2003; accepted Jun. 5, 2003.

This article has been cited by other articles:

				J. Chandrashekar, D. Yarmolinsky, L. von Buchholtz, Y. Oka, W. Sly, N. J. P. Ryba, and C. S. Zuker The Taste of Carbonation Science, October 16, 2009; 326(5951): 443 - 445. [Abstract] [Full Text] [PDF]

				T. Nakashiba, J. Z. Young, T. J. McHugh, D. L. Buhl, and S. Tonegawa Transgenic Inhibition of Synaptic Transmission Reveals Role of CA3 Output in Hippocampal Learning Science, February 29, 2008; 319(5867): 1260 - 1264. [Abstract] [Full Text] [PDF]

				K. Asakawa, M. L. Suster, K. Mizusawa, S. Nagayoshi, T. Kotani, A. Urasaki, Y. Kishimoto, M. Hibi, and K. Kawakami Genetic dissection of neural circuits by Tol2 transposon-mediated Gal4 gene and enhancer trapping in zebrafish PNAS, January 29, 2008; 105(4): 1255 - 1260. [Abstract] [Full Text] [PDF]

				N. Wada, Y. Kishimoto, D. Watanabe, M. Kano, T. Hirano, K. Funabiki, and S. Nakanishi Conditioned eyeblink learning is formed and stored without cerebellar granule cell transmission PNAS, October 16, 2007; 104(42): 16690 - 16695. [Abstract] [Full Text] [PDF]

				H. Mizuno, T. Hirano, and Y. Tagawa Evidence for Activity-Dependent Cortical Wiring: Formation of Interhemispheric Connections in Neonatal Mouse Visual Cortex Requires Projection Neuron Activity J. Neurosci., June 20, 2007; 27(25): 6760 - 6770. [Abstract] [Full Text] [PDF]

				F. C Crick and C. Koch What is the function of the claustrum? Phil Trans R Soc B, June 29, 2005; 360(1458): 1271 - 1279. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help