PUBLICATION
Chemical modulation of memory formation in larval zebrafish
- Authors
- Wolman, M.A., Jain, R.A., Liss, L., and Granato, M.
- ID
- ZDB-PUB-110901-30
- Date
- 2011
- 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
- MeSH Terms
-
- Acoustic Stimulation
- Animals
- Habituation, Psychophysiologic/drug effects
- Larva/drug effects
- Larva/physiology
- Latency Period, Psychological
- Mammals
- Memory/drug effects*
- Photic Stimulation
- Protein Biosynthesis/drug effects
- Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors
- Receptors, N-Methyl-D-Aspartate/metabolism
- Reflex, Startle/drug effects
- Small Molecule Libraries/pharmacology*
- Time Factors
- Zebrafish/physiology*
- PubMed
- 21876167 Full text @ Proc. Natl. Acad. Sci. USA
Citation
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.
Abstract
Whole 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping