Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory

Surgical, pharmacological and genetic lesion studies have revealed distinct anatomical sites involved with different forms of learning. Studies of patients with localized brain damage and work in rodent model systems, for example, have shown that the hippocampal formation participates in acquisition of declarative tasks but is not the site of their long-term storage. Such lesions are usually irreversible, however, which has limited their use for dissecting the temporal processes of acquisition, storage and retrieval of memories. Studies in bees and flies have similarly revealed a distinct anatomical region of the insect brain, the mushroom body, that is involved specifically in olfactory associative learning. We have used a temperature-sensitive dynamin transgene, which disrupts synaptic transmission reversibly and on the time-scale of minutes, to investigate the temporal requirements for ongoing neural activity during memory formation. Here we show that synaptic transmission from mushroom body neurons is required during memory retrieval but not during acquisition or storage. We propose that the hebbian processes underlying olfactory associative learning reside in mushroom body dendrites or upstream of the mushroom body and that the resulting alterations in synaptic strength modulate mushroom body output during memory retrieval.

[1]  T. Wiesel,et al.  Functional architecture of macaque monkey visual cortex , 1977 .

[2]  Alexander M. van der Bliek,et al.  Dynamin-like protein encoded by the Drosophila shibire gene associated with vesicular traffic , 1991, Nature.

[3]  L. Maffei,et al.  Neural Correlate of Perceptual Adaptation to Gratings , 1973, Science.

[4]  E. Kandel,et al.  Cognitive Neuroscience and the Study of Memory , 1998, Neuron.

[5]  J. Dubnau,et al.  Functional anatomy: From molecule to memory , 2001, Current Biology.

[6]  W. Scoville,et al.  Loss of Recent Memory After Bilateral Hippocampal Lesions , 2000 .

[7]  R. Kelly,et al.  Genetic studies on dynamin function in Drosophila. , 1993, Journal of neurogenetics.

[8]  S. Benzer BEHAVIORAL MUTANTS OF Drosophila ISOLATED BY COUNTERCURRENT DISTRIBUTION. , 1967, Proceedings of the National Academy of Sciences of the United States of America.

[9]  T. Kitamoto Conditional modification of behavior in Drosophila by targeted expression of a temperature-sensitive shibire allele in defined neurons. , 2001, Journal of neurobiology.

[10]  D. Brainard,et al.  Efficiency in detection of isoluminant and isochromatic interference fringes. , 1993, Journal of the Optical Society of America. A, Optics, image science, and vision.

[11]  R. Nicoll,et al.  Dynamin-dependent endocytosis of ionotropic glutamate receptors. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[12]  B. Swalla,et al.  Urochordates are monophyletic within the deuterostomes. , 2000, Systematic biology.

[13]  D M Levi,et al.  Humans deprived of normal binocular vision have binocular interactions tuned to size and orientation. , 1979, Science.

[14]  E. Shimizu,et al.  NMDA receptor-dependent synaptic reinforcement as a crucial process for memory consolidation. , 2000, Science.

[15]  M. Levine,et al.  Ascidian embryogenesis and the origins of the chordate body plan. , 1998, Current opinion in genetics & development.

[16]  M. Hammer,et al.  Multiple sites of associative odor learning as revealed by local brain microinjections of octopamine in honeybees. , 1998, Learning & memory.

[17]  H. Wada,et al.  Details of the evolutionary history from invertebrates to vertebrates, as deduced from the sequences of 18S rDNA. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[18]  Richard B. Vallee,et al.  Multiple forms of dynamin are encoded by shibire, a Drosophila gene involved in endocytosis , 1991, Nature.

[19]  B. Swalla,et al.  Evolution of the chordate body plan: new insights from phylogenetic analyses of deuterostome phyla. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[20]  F. Campbell,et al.  Optical quality of the human eye , 1966, The Journal of physiology.

[21]  K. Ikeda,et al.  Disappearance and reformation of synaptic vesicle membrane upon transmitter release observed under reversible blockage of membrane retrieval , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[22]  G. Edgecombe,et al.  A possible Early Cambrian chordate , 1995, Nature.

[23]  E. Kandel,et al.  Control of Memory Formation Through Regulated Expression of a CaMKII Transgene , 1996, Science.

[24]  P. Lennie,et al.  Fine Structure of Parvocellular Receptive Fields in the Primate Fovea Revealed by Laser Interferometry , 2000, The Journal of Neuroscience.

[25]  C. Blakemore,et al.  Adaptation to spatial stimuli. , 1969, The Journal of physiology.

[26]  R. Menzel,et al.  Anatomy of the mushroom bodies in the honey bee brain: The neuronal connections of the alpha‐lobe , 1993, The Journal of comparative neurology.

[27]  S. Schmid,et al.  Induction of mutant dynamin specifically blocks endocytic coated vesicle formation , 1994, The Journal of cell biology.

[28]  X. Hou,et al.  Arthropods of the Lower Cambrian Chengjiang fauna, southwest China , 1997, Fossils and Strata.

[29]  Jeremy M. Wolfe,et al.  Short test flashes produce large tilt aftereffects , 1984, Vision Research.

[30]  N. Strausfeld,et al.  The organization of extrinsic neurons and their implications in the functional roles of the mushroom bodies in Drosophila melanogaster Meigen. , 1998, Learning & memory.

[31]  D. Shu,et al.  Anatomy and systematic affinities of the Lower Cambrian bivalved arthropod Isoxys auritus , 1995 .

[32]  N. Strausfeld,et al.  Organization of olfactory and multimodal afferent neurons supplying the calyx and pedunculus of the cockroach mushroom bodies , 1999, The Journal of comparative neurology.

[33]  Tim Tully,et al.  Associative Learning Disrupted by Impaired Gs Signaling in Drosophila Mushroom Bodies , 1996, Science.

[34]  H. Wada Evolutionary history of free-swimming and sessile lifestyles in urochordates as deduced from 18S rDNA molecular phylogeny. , 1998, Molecular biology and evolution.

[35]  M. Jollie What are the ‘Calcichordata’? and the larger question of the origin of Chordates , 1982 .

[36]  R. Reid,et al.  Specificity of monosynaptic connections from thalamus to visual cortex , 1995, Nature.

[37]  J. Movshon,et al.  Pattern adaptation and cross-orientation interactions in the primary visual cortex , 1998, Neuropharmacology.

[38]  S. Morris,et al.  Lower Cambrian vertebrates from south China , 1999, Nature.

[39]  K. Müller Palaeobotryllus from the Upper Cambrian of Nevada — a probable ascidian , 1977 .

[40]  Leslie C. Griffith,et al.  Mapping of the anatomical circuit of CaM kinase-dependent courtship conditioning in Drosophila. , 1999, Learning & memory.

[41]  L. Edgar,et al.  Reversible alteration in the neuromuscular junctions of Drosophila melanogaster bearing a temperature-sensitive mutation, shibire , 1979, The Journal of cell biology.

[42]  T. Préat,et al.  Genetic dissection of consolidated memory in Drosophila , 1994, Cell.

[43]  M Heisenberg,et al.  Associative odor learning in Drosophila abolished by chemical ablation of mushroom bodies. , 1994, Science.

[44]  S. Morris,et al.  A pipiscid-like fossil from the Lower Cambrian of south China , 1999, Nature.

[45]  D. Linden,et al.  Expression of Cerebellar Long-Term Depression Requires Postsynaptic Clathrin-Mediated Endocytosis , 2000, Neuron.

[46]  M. Coltheart Visual feature-analyzers and after-effects of tilt and curvature. , 1971, Psychological review.

[47]  W. Quinn,et al.  The amnesiac Gene Product Is Expressed in Two Neurons in the Drosophila Brain that Are Critical for Memory , 2000, Cell.

[48]  D. Suzuki,et al.  Developmental properties of Shibire: a pleiotropic mutation affecting larval and adult locomotion and development. , 1973, Developmental biology.

[49]  D. Macleod,et al.  Local luminance nonlinearity and receptor aliasing in the detection of high-frequency gratings. , 1996, Journal of the Optical Society of America. A, Optics, image science, and vision.

[50]  D. Shu,et al.  Reinterpretation of Yunnanozoon as the earliest known hemichordate , 1996, Nature.

[51]  H S Smallman,et al.  Fine grain of the neural representation of human spatial vision , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[52]  H B Barlow,et al.  Single units and sensation: a neuron doctrine for perceptual psychology? , 1972, Perception.

[53]  N. Perrimon,et al.  Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. , 1993, Development.

[54]  N. Strausfeld,et al.  Subdivision of the drosophila mushroom bodies by enhancer-trap expression patterns , 1995, Neuron.

[55]  N. Satoh,et al.  Ascidian Homologs of Mammalian Thyroid Transcription Factor-1 Gene Are Expressed in the Endostyle , 1999 .

[56]  M. Ramaswami,et al.  Probable mechanisms underlying interallelic complementation and temperature-sensitivity of mutations at the shibire locus of Drosophila melanogaster. , 1998, Genetics.

[57]  W. Garstang Memoirs: The Morphology of the Tunicata, and its Bearings on the Phylogeny of the Chordata , 1928 .

[58]  Jian Han,et al.  New sites of Chengjiang fossils: crucial windows on the Cambrian explosion , 2001, Journal of the Geological Society.

[59]  Zhang Aiyun FOSSIL APPENDICULARIANS IN THE EARLY CAMBRIAN , 1987 .

[60]  S. Morris,et al.  A Pikaia-like chordate from the Lower Cambrian of China , 1996, Nature.

[61]  C. Koch,et al.  Are we aware of neural activity in primary visual cortex? , 1995, Nature.

[62]  M Heisenberg,et al.  Localization of a short-term memory in Drosophila. , 2000, Science.

[63]  P. Lennie,et al.  Pattern-selective adaptation in visual cortical neurones , 1979, Nature.