期刊
JOURNAL OF NEUROSCIENCE
卷 27, 期 18, 页码 4984-4994出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.0615-07.2007
关键词
zebrafish; prepulse inhibition; behavior; sensorimotor gating; dopamine; startle response
资金
- NIMH NIH HHS [R01 MH075691-01, R01 MH075691-05, R01 MH075691, R01 MH075691-03, R01 MH075691-02, MH-075691, R01 MH075691-04] Funding Source: Medline
- NINDS NIH HHS [R21 NS048258, NS-048258] Funding Source: Medline
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.
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