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.
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
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.