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Defective glycinergic synaptic transmission in zebrafish motility mutants
Journal article   Open access   Peer reviewed

Defective glycinergic synaptic transmission in zebrafish motility mutants

H Hirata, E Carta, I Yamanaka, Robert J Harvey and J Y Kuwada
Frontiers in Molecular Neuroscience, Vol.2, 26
2010
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https://doi.org/10.3389/neuro.02.026.2009View
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Abstract

behavior glycine motility receptor synapse transporter zebrafish
Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, in vivoanalysis of glycinergic synaptic transmission has been pursued in zebrafish using moleculargenetics. An ENU mutagenesis screen identified two behavioral mutants that are defective inglycinergic synaptic transmission. Zebrafish bandoneon (beo) mutants have a defect in glrbb,one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss ofglycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to theconsequent loss of reciprocal inhibition of motor circuits between the two sides of the spinalcord, motor neurons activate simultaneously on both sides resulting in bilateral contraction ofaxial muscles of beo mutants, eliciting the so-called 'accordion' phenotype. Similar defectsin GlyR subunit genes have been observed in several mammals and are the basis for humanhyperekplexia/startle disease. By contrast, zebrafish shocked (sho) mutants have a defect inslc6a9, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding theglycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine fromthe synaptic cleft, terminating synaptic transmission. In zebrafish sho mutants, there appearsto be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons andsubsequent reduced motility, causing the 'twitch-once' phenotype. We review current knowledgeregarding zebrafish 'accordion' and 'twitch-once' mutants, including beo and sho, and reportthe identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs. © 2010 Hirata, Carta, Yamanaka, Harvey and Kuwada.

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