|ZFIN ID: ZDB-PUB-110901-30|
Chemical modulation of memory formation in larval zebrafish
Wolman, M.A., Jain, R.A., Liss, L., and Granato, M.
|Source:||Proceedings of the National Academy of Sciences of the United States of America 108(37): 15468-73 (Journal)|
|Registered Authors:||Granato, Michael, Jain, Roshan, Wolman, Marc|
|Keywords:||acoustic startle response, sensorimotor gating|
|PubMed:||21876167 Full text @ Proc. Natl. Acad. Sci. USA|
Wolman, M.A., Jain, R.A., Liss, L., and Granato, M. (2011) Chemical modulation of memory formation in larval zebrafish. Proceedings of the National Academy of Sciences of the United States of America. 108(37):15468-73.
ABSTRACTWhole organism–based small-molecule screens have proven powerful in identifying novel therapeutic chemicals, yet this approach has not been exploited to identify new cognitive enhancers. Here we present an automated high-throughput system for measuring nonassociative learning behaviors in larval zebrafish. Using this system, we report that spaced training blocks of repetitive visual stimuli elicit protein synthesis–dependent long-term habituation in larval zebrafish, lasting up to 24 h. Moreover, repetitive acoustic stimulation induces robust short-term habituation that can be modulated by stimulation frequency and instantaneously dishabituated through cross-modal stimulation. To characterize the neurochemical pathways underlying short-term habituation, we screened 1,760 bioactive compounds with known targets. Although we found extensive functional conservation of short-term learning between larval zebrafish and mammalian models, we also discovered several compounds with previously unknown roles in learning. These compounds included a myristic acid analog known to interact with Src family kinases and an inhibitor of cyclin dependent kinase 2, demonstrating that high-throughput chemical screens combined with high-resolution behavioral assays provide a powerful approach for the discovery of novel cognitive modulators.
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