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1 Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA; Cell and Molecular Biology Graduate Program, University of Michigan, Ann Arbor, MI, USA
2 Department of Molecular, Cellular and Developmental Biology, University of Michigan, Ann Arbor, MI, USA
* To whom correspondence should be addressed. E-mail: kuwada{at}umich.edu.
The analysis of behavioral mutations in zebrafish can be a powerful strategy for identifying genes that regulate the function and development of neural circuits in the vertebrate CNS. A neurophysiological analysis of the shocked (sho) mutation that affects the initiation of swimming following mechanosensory stimulation was undertaken to identify the function of the sho gene product in the developing motor circuitry. The cutaneous Rohon-Beard (RB) mechanosensory neurons responded normally to stimulation and muscle fibers were unaffected in sho embryos suggesting that the output of the CNS is abnormal. Indeed whole cell patch recordings from mutant muscle cells showed normal spontaneous miniature endplate potentials, but abnormal touch-evoked endplate potentials. Furthermore, motor neuron recordings showed that bursts of rhythmic action potentials from synaptically-dependent depolarizations are initiated in wildtype motor neurons following sensory stimulation or bath application of NMDA. These bursts presumably correspond to bouts of swimming. In sho motor neurons the touch-evoked depolarizations were not sustained resulting in an abbreviated burst of action potentials. The defective responses were not due to any obvious defect in sho motor neurons since their basic properties were normal. These results suggest that in sho embryos there is aberrant motor processing within the CNS and that normal motor processing requires the sho gene product.
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