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The Journal of Neuroscience, February 27, 2008, 28(9):2110-2118; doi:10.1523/JNEUROSCI.5230-07.2008

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Cellular/Molecular
Vesicular Glutamate Transporter 3 Is Required for Synaptic Transmission in Zebrafish Hair Cells

Nikolaus Obholzer,¹ Sean Wolfson,¹ Josef G. Trapani,¹ Weike Mo,¹ Alex Nechiporuk,² Elisabeth Busch-Nentwich,³ Christoph Seiler,³ Samuel Sidi,³ Christian Söllner,³ Robert N. Duncan,¹ Andrea Boehland,¹ and Teresa Nicolson¹

¹Howard Hughes Medical Institute, Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, Portland, Oregon 97239, ²Department of Biological Structure, University of Washington, Seattle, Washington 98195, and ³Max-Planck-Institut für Entwicklungsbiologie, 72076 Tübingen, Germany

Correspondence should be addressed to Teresa Nicolson, Howard Hughes Medical Institute, Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239. Email: nicolson{at}ohsu.edu

Hair cells detect sound and movement and transmit this information via specialized ribbon synapses. Here we report that asteroid, a gene identified in an ethylnitrosourea mutagenesis screen of zebrafish larvae for auditory/vestibular mutants, encodes vesicular glutamate transporter 3 (Vglut3). A splice site mutation in exon 2 of vglut3 results in a severe truncation of the predicted protein product and morpholinos directed against the vglut3 ATG start site or the affected splice junction replicate the asteroid phenotype. In situ hybridization shows that vglut3 is exclusively expressed in hair cells of the ear and lateral line organ. A second transporter gene, vglut1, is also expressed in zebrafish hair cells, but the level of vglut1 mRNA is not increased in the absence of Vglut3. Antibodies against Vglut3 label the basal end of hair cells and labeling is not present in asteroid/vglut3 mutants. Based on the localization of Vglut3 in hair cells, we suspected that the lack of vestibulo-ocular and acoustic startle reflexes in asteroid/vglut3 mutants was attributable to a defect in synaptic transmission in hair cells. In support of this notion, action currents in postsynaptic acousticolateralis neurons are absent in asteroid/vglut3 mutants. At the ultrastructural level, mutant asteroid/vglut3 hair cells show a decrease in the number of ribbon-associated synaptic vesicles, indicating a role for Vglut3 in synaptic vesicle biogenesis and/or tethering to the ribbon body. Lack of postsynaptic action currents in the mutants suggests that the remaining hair-cell synaptic vesicles contain insufficient levels of glutamate for generation of action potentials in first-order neurons.

Key words: vglut3; zebrafish; action currents; hair cells; synaptic vesicles; ribbon synapse; vglut1

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Received July 5, 2007; revised Jan. 15, 2008; accepted Jan. 16, 2008.

Correspondence should be addressed to Teresa Nicolson, Howard Hughes Medical Institute, Oregon Hearing Research Center and Vollum Institute, Oregon Health & Science University, 3181 Southwest Sam Jackson Park Road, Portland, OR 97239. Email: nicolson{at}ohsu.edu

This article has been cited by other articles:

				M. Tanimoto, Y. Ota, K. Horikawa, and Y. Oda Auditory Input to CNS Is Acquired Coincidentally with Development of Inner Ear after Formation of Functional Afferent Pathway in Zebrafish J. Neurosci., March 4, 2009; 29(9): 2762 - 2767. [Abstract] [Full Text] [PDF]

				A. Nagiel, D. Andor-Ardo, and A. J. Hudspeth Specificity of Afferent Synapses onto Plane-Polarized Hair Cells in the Posterior Lateral Line of the Zebrafish J. Neurosci., August 20, 2008; 28(34): 8442 - 8453. [Abstract] [Full Text] [PDF]

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