We are applying the economy-of-scale of the Drosophila model system to identify genes involved in plasticity. We have developed a Pavlovian olfactory learning assay that shows a wide variety of behavioral properties seen for associative learning across the animal kingdom. Most of the genes identified to date have been shown to be involved in various forms of behavioral or synaptic plasticity in both vertebrate and invertebrate model systems. We have identified a gene, Adf1, that plays a clear role in adult long-term memory formation (behavioral plasticity) and in synapse formation at the larval neuromuscular junction (developmental plasticity). The Adf1 gene encodes a transcription factor with no other known biological functions. We hypothesize that Adf1 is a molecular component of activity-dependent synaptic plasticity. We propose further experiments to (i) determine whether Adf1 interacts with other molecular components involved in synaptic plasticity, such as the cAMP (PKA) or jun kinase (JNK) signaling pathways, the CREB transcription pathway or cell adhesion molecules and (ii) visualize Adf1-dependent gene expression during developmental or behavioral. Ultimately, such knowledge will help to reveal various forms of cognitive dysfunction that result from heredity, disease, injury or age. Since the brain is a highly plastic organ, we eventually will be able to intervene with behavioral, pharmacological or even gene therapies to ameliorate specific forms of cognitive dysfunction by manipulating the underlying cellular plasticities.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Project (R01)
Project #
5R01MH066242-02
Application #
6704725
Study Section
Special Emphasis Panel (ZRG1-IFCN-7 (02))
Program Officer
Beckel-Mitchener, Andrea C
Project Start
2003-03-01
Project End
2008-02-29
Budget Start
2004-04-12
Budget End
2005-02-28
Support Year
2
Fiscal Year
2004
Total Cost
$380,438
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
Zhao, Hong; Zheng, Xingguo; Yuan, Xiaojing et al. (2009) ben Functions with scamp during synaptic transmission and long-term memory formation in Drosophila. J Neurosci 29:414-24
Asztalos, Zoltan; Arora, Neeraj; Tully, Tim (2007) Olfactory jump reflex habituation in Drosophila and effects of classical conditioning mutations. J Neurogenet 21:1-18
Asztalos, Zoltan; Baba, Kotaro; Yamamoto, Daisuke et al. (2007) The fickle mutation of a cytoplasmic tyrosine kinase effects sensitization but not dishabituation in Drosophila melanogaster. J Neurogenet 21:59-71
Joiner, M A; Asztalos, Z; Jones, C J et al. (2007) Effects of mutant Drosophila K+ channel subunits on habituation of the olfactory jump response. J Neurogenet 21:45-58