AUTHOR=Hirata Hiromi , Carta Eloisa , Yamanaka Iori , Harvey Robert J., Kuwada John Y.

TITLE=Defective glycinergic synaptic transmission in zebrafish motility mutants

JOURNAL=Frontiers in Molecular Neuroscience

VOLUME=2

YEAR=2010

URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/neuro.02.026.2009

DOI=10.3389/neuro.02.026.2009

ISSN=1662-5099

ABSTRACT=<p>Glycine is a major inhibitory neurotransmitter in the spinal cord and brainstem. Recently, <italic>in vivo</italic> analysis of glycinergic synaptic transmission has been pursued in zebrafish using molecular genetics. An ENU mutagenesis screen identified two behavioral mutants that are defective in glycinergic synaptic transmission. Zebrafish <italic>bandoneon (beo)</italic> mutants have a defect in <italic>glrbb</italic>, one of the duplicated glycine receptor (GlyR) β subunit genes. These mutants exhibit a loss of glycinergic synaptic transmission due to a lack of synaptic aggregation of GlyRs. Due to the consequent loss of reciprocal inhibition of motor circuits between the two sides of the spinal cord, motor neurons activate simultaneously on both sides resulting in bilateral contraction of axial muscles of <italic>beo</italic> mutants, eliciting the so-called ‘accordion’ phenotype. Similar defects in GlyR subunit genes have been observed in several mammals and are the basis for human hyperekplexia/startle disease. By contrast, zebrafish <italic>shocked (sho)</italic> mutants have a defect in <italic>slc6a9</italic>, encoding GlyT1, a glycine transporter that is expressed by astroglial cells surrounding the glycinergic synapse in the hindbrain and spinal cord. GlyT1 mediates rapid uptake of glycine from the synaptic cleft, terminating synaptic transmission. In zebrafish <italic>sho</italic> mutants, there appears to be elevated extracellular glycine resulting in persistent inhibition of postsynaptic neurons and subsequent reduced motility, causing the ‘twitch-once’ phenotype. We review current knowledge regarding zebrafish ‘accordion’ and ‘twitch-once’ mutants, including <italic>beo</italic> and <italic>sho</italic>, and report the identification of a new α2 subunit that revises the phylogeny of zebrafish GlyRs.</p>