Behavioral assays have been developed to proceed with an integrated, selective molecular genetic analysis of learning and memory processes in Drosophila. Initial results have revealed substantial functional homology between fruit flies and vertebrates for these behavioral properties of learning and memory (see Preliminary Results). A better understanding of the functional relations between molecular processes and learning/memory processes will emerge by determining more precisely which properties are disrupted by particular single-gene mutations. Assays for discriminative Pavlovian conditioning, acquisition, extinction, US pre- exposure, blocking and overshadowing, conditioned inhibition, conditioned excitation, retrograde amnesia, long-term memory, trace conditioning and habituation, dishabituation and spontaneous recovery already have been developed, and results from wild-type (normal) flies are presented. Ne assays for CS-pre-exposure, CS preconditioning, second-order conditioning, short-term memory, middle-term memory and sensitization also will be developed. The learning/memory mutants dunce rutabaga, radish, amnesiac, latheo, linotte, nalyot and golovan, the ion channel mutants Shaker, ether-a-gogo and no action potential, the brain-structure mutants mushrooms body degraded, mushroom body miniature, calyx, bulging, minibrain, central body defect, no bridge and central complex broad and biochemical mutants of the RI regulatory subunit of cAMP-dependent protein kinase (PKA) and the catalytic subunit of PKA will be characterized with this battery of behavioral assays. This experimental approach promises a genic dissection of the functional relations between molecular processes and learning/memory processes and of the functional relations among the various behavioral properties themselves. Considering the substantial molecular homologies among fruit fly, other invertebrate and vertebrate learning and memory processes, we expect the knowledge derived from our work with fruit flies to suggest a biological organization of vertebrate cognition. Importantly, this experimental approach is unique to the field of cognitive neuropsychology.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD032245-02
Application #
2205266
Study Section
Special Emphasis Panel (SRC (22))
Project Start
1994-04-01
Project End
1997-03-31
Budget Start
1995-04-01
Budget End
1996-03-31
Support Year
2
Fiscal Year
1995
Total Cost
Indirect Cost
Name
Cold Spring Harbor Laboratory
Department
Type
DUNS #
065968786
City
Cold Spring Harbor
State
NY
Country
United States
Zip Code
11724
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Connolly, J B; Tully, T (1998) Integrins: a role for adhesion molecules in olfactory memory. Curr Biol 8:R386-9
Goodwin, S F; Del Vecchio, M; Velinzon, K et al. (1997) Defective learning in mutants of the Drosophila gene for a regulatory subunit of cAMP-dependent protein kinase. J Neurosci 17:8817-27
Mihalek, R M; Jones, C J; Tully, T (1997) The Drosophila mutation turnip has pleiotropic behavioral effects and does not specifically affect learning. Learn Mem 3:425-44
Connolly, J B; Roberts, I J; Armstrong, J D et al. (1996) Associative learning disrupted by impaired Gs signaling in Drosophila mushroom bodies. Science 274:2104-7
Yin, J C; Tully, T (1996) CREB and the formation of long-term memory. Curr Opin Neurobiol 6:264-8
Tully, T; Bolwig, G; Christensen, J et al. (1996) A return to genetic dissection of memory in Drosophila. Cold Spring Harb Symp Quant Biol 61:207-18
DeZazzo, J; Tully, T (1995) Dissection of memory formation: from behavioral pharmacology to molecular genetics. Trends Neurosci 18:212-8
Yin, J C; Del Vecchio, M; Zhou, H et al. (1995) CREB as a memory modulator: induced expression of a dCREB2 activator isoform enhances long-term memory in Drosophila. Cell 81:107-15
Yin, J C; Wallach, J S; Del Vecchio, M et al. (1994) Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila. Cell 79:49-58

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