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The Journal of Neuroscience, May 2, 2007, 27(18):4984-4994; doi:10.1523/JNEUROSCI.0615-07.2007

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Behavioral/Systems/Cognitive
Sensorimotor Gating in Larval Zebrafish

Harold A. Burgess and Michael Granato

Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6058

Correspondence should be addressed to Michael Granato at the above address. Email: granatom{at}mail.med.upenn.edu

Control of behavior in the natural environment where sensory stimuli are abundant requires superfluous information to be ignored. In part, this is achieved through selective transmission, or gating of signals to motor systems. A quantitative and clinically important measure of sensorimotor gating is prepulse inhibition (PPI) of the startle response, impairments in which have been demonstrated in several neuropsychiatric disorders, including schizophrenia. Here, we show for the first time that the acoustic startle response in zebrafish larvae is modulated by weak prepulses in a manner similar to mammalian PPI. We demonstrate that, like in mammals, antipsychotic drugs can suppress disruptions in zebrafish PPI induced by dopamine agonists. Because genetic factors underlying PPI are not well understood, we performed a screen and isolated mutant lines with reduced PPI. Analysis of Ophelia mutants demonstrates that they have normal sensory acuity and startle performance, but reduced PPI, suggesting that Ophelia is critical for central processing of sensory information. Thus, our results provide the first evidence for sensorimotor gating in larval zebrafish and report on the first unbiased screen to identify genes regulating this process.

Key words: zebrafish; prepulse inhibition; behavior; sensorimotor gating; dopamine; startle response

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Received Oct. 3, 2006; revised March 20, 2007; accepted March 26, 2007.

Correspondence should be addressed to Michael Granato at the above address. Email: granatom{at}mail.med.upenn.edu

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