learning

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PART 4 BEHAVIORAL PLASTICITY 23 MOLECULAR
GENETICS OF LEARNING MEMORY IN DROSOPHILA II

• learning memory in flies
• environmental sources of plasticity
• genetic dissection of learning memory
• anatomical mutants
• biochemical mutants
• molecular dissection of memory
• summary

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PART 4 BEHAVIORAL PLASTICITY 23 MOLECULAR
GENETICS OF LEARNING MEMORY IN DROSOPHILA II

• learning memory in flies
• environmental sources of plasticity
• genetic dissection of learning memory
• anatomical mutants
• biochemical mutants
• molecular dissection of memory
• summary

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PAVLOVS FLIES
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2 CLASSES OF L M MUTANTS

• anatomical mutants
• screens for anatomical defects
• biochemical mutants
• screens for behavioral defects

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2 CLASSES OF L M MUTANTS

• anatomical mutants
• screens for anatomical defects
• biochemical mutants
• screens for behavioral defects

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BIOCHEMICAL MUTANTS
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MEMORY PHASES

• genetically distinct memory phases

J. Dubnau T. Tully
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... GENETIC DISSECTION
massed training rsh PKC cer stau N pum ADF-1
neb CREB CXM spaced training
PKA-C1 PKA-R1 mbm G?s fas II leo vol lat lio
dnc rut
amn PKA-C1
? ACQ ? STM ? MTM
adapted from Margulies et al. 2005
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MEMORY GENES SIGNALING
S. Waddell
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DROSOPHILA vs APLYSIA
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MEMORY GENE EXPRESSION ? IN MBs
Crittenden et al. 1998
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cAMP-DEPENDENT PROTEIN KINASE (PKA)

• one of first transgenic experiments in flies
• transform flies with
• gene for peptide inhibitor of PKA
• under control of heat-shock promoter...
• temporal resolution

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cAMP-DEPENDENT PROTEIN KINASE (PKA)
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cAMP-DEPENDENT PROTEIN KINASE (PKA)
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cAMP-DEPENDENT PROTEIN KINASE (PKA)
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cAMP-DEPENDENT PROTEIN KINASE (PKA)

• one of first transgenic experiments in flies
• transform flies with
• gene for peptide inhibitor of PKA
• under control of heat-shock promoter...
• temporal resolution
• test associative learning
• permissive temperature normal learning

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cAMP-DEPENDENT PROTEIN KINASE (PKA)
?

• permissive temperature normal learning

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cAMP-DEPENDENT PROTEIN KINASE (PKA)

• one of first transgenic experiments in flies
• transform flies with
• gene for peptide inhibitor of PKA
• under control of heat-shock promoter...
• temporal resolution
• test associative learning
• permissive temperature normal learning
• restrictive temperature blocked learning

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cAMP-DEPENDENT PROTEIN KINASE (PKA)
?

• restrictive temperature learning blocked

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CREB cAMP-RESPONSE ELEMENT BINDING PROTEIN

• single cycle training not protein synthesis
  dependent
• ARM resistant to cold shock
• ARM not protein synthesis dependent

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CREB cAMP-RESPONSE ELEMENT BINDING PROTEIN

• long-lasting memory in radish mutants
• radish encodes some aspect of ARM

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CREB cAMP-RESPONSE ELEMENT BINDING PROTEIN

• transgenic flies heat-shock activated dominant
  negative CREB isoform blocks LTM

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CREB cAMP-RESPONSE ELEMENT BINDING PROTEIN

• 2 kinds of long-lasting memory
• massed training ? ARM, resistant to cold shock
• spaced training ? LTM, protein synthesis
  dependent

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CREB cAMP-RESPONSE ELEMENT BINDING PROTEIN

• transgenic conditional CREB blockers LTM
• radish mutants have no ARM

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GAL4 ENHANCER TRAP SYSTEM
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GAL4 ENHANCER TRAP SYSTEM
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GAL4 ENHANCER TRAP SYSTEM
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GAL4 ENHANCER TRAP SYSTEM
/
w
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GAL4 ENHANCER TRAP SYSTEM
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GAL4 ENHANCER TRAP SYSTEM
/
? ?
w E X
x
/
w
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GAL4 ENHANCER TRAP SYSTEM
/
w E X
/
w
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MB-SPECIFIC CELL MARKERS
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G-PROTEINS cAMP PATHWAY
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MB-TARGETED G?s
/
w E X
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w
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MB-TARGETED G?s
Connolly et al.
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ADENYLYL CYCLASE cAMP PATHWAY
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MB TARGETED rut RESCUE
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w E X
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w
rut
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MB TARGETED rut RESCUE
Zars et al
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MB NEURON SIGNALING LEARNING
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w E X
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w
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MB NEURON SIGNALING LEARNING
Dubnau et al.
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MB NEURON SIGNALING RETRIEVAL
Dubnau et al.
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... GENETIC DISSECTION
massed training rsh PKC cer stau N pum ADF-1
neb CREB CXM spaced training
PKA-C1 PKA-R1 mbm G?s fas II leo vol lat lio
dnc rut
amn PKA-C1
? ACQ ? STM ? MTM
adapted from Margulies et al. 2005
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MEMORY GENES SIGNALING
S. Waddell
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BUILDING A MEMORY CIRCUIT
A.S. Chiang
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SUMMARY

• flies can learn a variety of tasks
• classical differential conditioning of odor
  avoidance
• genetic dissection mutants impaired in
• cAMP cascade
• mushroom body neuroanatomy
• ... all have correlated learning / memory
  defects
• homology with other species / model systems
• memory phases
• single cycle training
• massed spaced training

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SUMMARY

• transgenic studies
• PKA
• CREB
• molecular biology anatomy functions defined
  at
• cellular level neurons are equivalent
• or
• structural level neurons are different

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SUMMARY

• integrated research approach in flies

• convergence...
• behavior
• anatomy
• cell biology

• at all levels of organization...
• components characterized
• plasticity

• prospects
• homology
• applications