Consolidated and Labile Odor Memory Are Separately Encoded within the Drosophila Brain

Memories are classified as consolidated (stable) or labile according to whether they withstand amnestic treatment, or not. In contrast to the general prevalence of this classification, its neuronal and molecular basis is poorly understood. Here, we focused on consolidated and labile memories induced after a single cycle training in the Drosophila aversive olfactory conditioning paradigm and we used mutants to define the impact of cAMP signals. At the biochemical level we report that cAMP signals misrelated in either rutabaga (rut) or dunce (dnc) mutants separate between consolidated anesthesia-resistant memory (ARM) and labile anesthesia-sensitive memory (ASM). Those functionally distinct cAMP signals act within different neuronal populations: while rut-dependent cAMP signals act within Kenyon cells (KCs) of the mushroom bodies to support ASM, dnc-sensitive cAMP signals support ARM within antennal lobe local neurons (LNs) and KCs. Collectively, different key positions along the olfactory circuitry seem to get modified during storage of ARM or ASM independently. A precise separation between those functionally distinct cAMP signals seems mandatory to allocate how they support appropriate memories.

[1]  Ronald L. Davis,et al.  Roles for Drosophila mushroom body neurons in olfactory learning and memory. , 2006, Learning & memory.

[2]  E. Hallem,et al.  The Spatial Code for Odors Is Changed by Conditioning , 2004, Neuron.

[3]  Hiromu Tanimoto,et al.  Experimental psychology: Event timing turns punishment to reward , 2004, Nature.

[4]  B. Dauwalder,et al.  Conditional rescue of the dunce learning/memory and female fertility defects with Drosophila or rat transgenes , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[5]  H. Atwood,et al.  Drosophila larval neuromuscular junction's responses to reduction of cAMP in the nervous system. , 1999, Journal of neurobiology.

[6]  Gilles Laurent,et al.  Transformation of Olfactory Representations in the Drosophila Antennal Lobe , 2004, Science.

[7]  M. Houslay,et al.  Regulation of a Drosophila melanogaster cGMP-specific phosphodiesterase by prenylation and interaction with a prenyl-binding protein. , 2008, The Biochemical journal.

[8]  R. Davis,et al.  Characterization of the memory gene dunce of Drosophila melanogaster. , 1991, Journal of molecular biology.

[9]  Yoshinori Aso,et al.  The Mushroom Body of Adult Drosophila Characterized by GAL4 Drivers , 2009, Journal of neurogenetics.

[10]  Ronald L. Davis,et al.  Dynamics of Learning-Related cAMP Signaling and Stimulus Integration in the Drosophila Olfactory Pathway , 2009, Neuron.

[11]  M. Livingstone,et al.  Loss of calcium/calmodulin responsiveness in adenylate cyclase of rutabaga, a Drosophila learning mutant , 1984, Cell.

[12]  W. Quinn,et al.  Reward learning in normal and mutant Drosophila. , 1983, Proceedings of the National Academy of Sciences of the United States of America.

[13]  D. Featherstone,et al.  Tomosyn-dependent regulation of synaptic transmission is required for a late phase of associative odor memory , 2011, Proceedings of the National Academy of Sciences.

[14]  R. Carthew,et al.  Making a better RNAi vector for Drosophila: use of intron spacers. , 2003, Methods.

[15]  K. Siwicki,et al.  Mushroom Body Ablation Impairs Short-Term Memory and Long-Term Memory of Courtship Conditioning in Drosophila melanogaster , 1999, Neuron.

[16]  R. Davis,et al.  Genetic dissection of the learning/memory gene dunce of Drosophila melanogaster. , 1993, Genes & development.

[17]  Ronald L. Davis,et al.  Traces of Drosophila Memory , 2011, Neuron.

[18]  Wei Zhang,et al.  Functional feedback from mushroom bodies to antennal lobes in the Drosophila olfactory pathway , 2010, Proceedings of the National Academy of Sciences.

[19]  B. Gerber,et al.  Cellular site and molecular mode of synapsin action in associative learning. , 2011, Learning & memory.

[20]  Zhefeng Gong,et al.  Differential roles of the fan-shaped body and the ellipsoid body in Drosophila visual pattern memory. , 2009, Learning & memory.

[21]  D. Storm,et al.  Calcium-Stimulated Adenylyl Cyclases Are Critical Modulators of Neuronal Ethanol Sensitivity , 2005, The Journal of Neuroscience.

[22]  Martin Schwaerzel,et al.  Signaling at A-Kinase Anchoring Proteins Organizes Anesthesia-Sensitive Memory in Drosophila , 2007, The Journal of Neuroscience.

[23]  Thomas Preat,et al.  PKA Dynamics in a Drosophila Learning Center: Coincidence Detection by Rutabaga Adenylyl Cyclase and Spatial Regulation by Dunce Phosphodiesterase , 2010, Neuron.

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

[25]  Ronald L. Davis,et al.  The cyclic AMP phosphodiesterase encoded by the drosophila dunce gene is concentrated in the mushroom body neuropil , 1991, Neuron.

[26]  W. Quinn,et al.  Classical conditioning and retention in normal and mutantDrosophila melanogaster , 1985, Journal of Comparative Physiology A.

[27]  R. Latorre,et al.  A cyclic AMP-activated K+ channel in Drosophila larval muscle is persistently activated in dunce. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[28]  U. Müller.  Prolonged Activation of cAMP-Dependent Protein Kinase during Conditioning Induces Long-Term Memory in Honeybees , 2000, Neuron.

[29]  G. Laurent,et al.  Normalization for Sparse Encoding of Odors by a Wide-Field Interneuron , 2011, Science.

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

[31]  Gilles Laurent,et al.  A Simple Connectivity Scheme for Sparse Coding in an Olfactory System , 2007, The Journal of Neuroscience.

[32]  D. Yamazaki,et al.  Acute Inhibition of PKA Activity at Old Ages Ameliorates Age-Related Memory Impairment in Drosophila , 2010, The Journal of Neuroscience.

[33]  Thomas Preat,et al.  Exclusive Consolidated Memory Phases in Drosophila , 2004, Science.

[34]  G. Technau.  Fiber number in the mushroom bodies of adult Drosophila melanogaster depends on age, sex and experience. , 1984, Journal of neurogenetics.

[35]  S. Knapek,et al.  Bruchpilot, A Synaptic Active Zone Protein for Anesthesia-Resistant Memory , 2011, The Journal of Neuroscience.

[36]  Glenn C. Turner,et al.  Olfactory representations by Drosophila mushroom body neurons. , 2008, Journal of neurophysiology.

[37]  L. Vosshall,et al.  Molecular architecture of smell and taste in Drosophila. , 2007, Annual review of neuroscience.

[38]  Y. Zhong,et al.  Altered synaptic plasticity in Drosophila memory mutants with a defective cyclic AMP cascade. , 1991, Science.

[39]  Ronald L. Davis,et al.  Spatiotemporal Gene Expression Targeting with the TARGET and Gene-Switch Systems in Drosophila , 2004, Science's STKE.

[40]  Ronald L. Davis,et al.  The GABAA Receptor RDL Suppresses the Conditioned Stimulus Pathway for Olfactory Learning , 2009, The Journal of Neuroscience.

[41]  Ronald L. Davis,et al.  Spatiotemporal Rescue of Memory Dysfunction in Drosophila , 2003, Science.

[42]  Ghislain Belliart-Guérin,et al.  Slow oscillations in two pairs of dopaminergic neurons gate long-term memory formation in Drosophila , 2012, Nature Neuroscience.

[43]  Ronald L. Davis,et al.  The GABAergic anterior paired lateral neuron suppresses and is suppressed by olfactory learning , 2008, Nature Neuroscience.

[44]  Ronald L. Davis,et al.  Drosophila DPM Neurons Form a Delayed and Branch-Specific Memory Trace after Olfactory Classical Conditioning , 2005, Cell.

[45]  Jason Sih-Yu Lai,et al.  Heterotypic Gap Junctions between Two Neurons in the Drosophila Brain Are Critical for Memory , 2011, Current Biology.

[46]  Yoshinori Aso,et al.  Three Dopamine Pathways Induce Aversive Odor Memories with Different Stability , 2012, PLoS genetics.

[47]  Kei Ito,et al.  Activity-Dependent Plasticity in an Olfactory Circuit , 2007, Neuron.

[48]  R. Davis,et al.  Physiology and biochemistry of Drosophila learning mutants. , 1996, Physiological reviews.

[49]  Y. Jan,et al.  dunce, a mutant of Drosophila deficient in learning. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[50]  B. Smith,et al.  Associative Conditioning Tunes Transient Dynamics of Early Olfactory Processing , 2009, The Journal of Neuroscience.

[51]  L. Luo,et al.  Diversity and Wiring Variability of Olfactory Local Interneurons in the Drosophila Antennal Lobe , 2010, Nature Neuroscience.

[52]  M. Heisenberg,et al.  Dopamine and Octopamine Differentiate between Aversive and Appetitive Olfactory Memories in Drosophila , 2003, The Journal of Neuroscience.

[53]  Andreas S. Thum,et al.  Differential potencies of effector genes in adult Drosophila , 2006, The Journal of comparative neurology.

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

[55]  Ronald L. Davis,et al.  Altered Representation of the Spatial Code for Odors after Olfactory Classical Conditioning Memory Trace Formation by Synaptic Recruitment , 2004, Neuron.

[56]  M. Houslay.  Underpinning compartmentalised cAMP signalling through targeted cAMP breakdown. , 2010, Trends in biochemical sciences.

[57]  R. Bourtchouladze,et al.  Targeting the CREB pathway for memory enhancers , 2003, Nature Reviews Drug Discovery.

[58]  J. Raymond.  [Cyclic AMP]. , 1972, La Nouvelle presse medicale.

[59]  G. Laurent,et al.  Role of GABAergic Inhibition in Shaping Odor-Evoked Spatiotemporal Patterns in the Drosophila Antennal Lobe , 2005, The Journal of Neuroscience.

[60]  Wanhe Li,et al.  Short- and Long-Term Memory in Drosophila Require cAMP Signaling in Distinct Neuron Types , 2009, Current Biology.

[61]  W. Quinn,et al.  Induction of a dominant negative CREB transgene specifically blocks long-term memory in Drosophila , 1994, Cell.

[62]  S. Waddell,et al.  Sequential Use of Mushroom Body Neuron Subsets during Drosophila Odor Memory Processing , 2007, Neuron.

[63]  J. Dow,et al.  Cyclic nucleotide phosphodiesterases in Drosophila melanogaster. , 2005, The Biochemical journal.

[64]  Yoshinori Aso,et al.  Specific Dopaminergic Neurons for the Formation of Labile Aversive Memory , 2010, Current Biology.

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

[66]  E. Kandel,et al.  Is contiguity detection in classical conditioning a system or a cellular property? Learning in Aplysia suggests a possible molecular site , 1988, Trends in Neurosciences.

[67]  D. Yamazaki,et al.  Protein kinase A inhibits a consolidated form of memory in Drosophila , 2008, Proceedings of the National Academy of Sciences.

[68]  M. Heisenberg,et al.  Conditioned visual flight orientation in Drosophila: dependence on age, practice, and diet. , 1996, Learning & memory.

[69]  B. Gerber,et al.  Synapsin is selectively required for anesthesia-sensitive memory. , 2010, Learning & memory.

[70]  L. Squire,et al.  100 years of consolidation--remembering Müller and Pilzecker. , 1999, Learning & memory.

[71]  G. Rubin,et al.  Mushroom body efferent neurons responsible for aversive olfactory memory retrieval in Drosophila , 2011, Nature Neuroscience.

[72]  R. Menzel,et al.  Associative learning modifies neural representations of odors in the insect brain , 1999, Nature Neuroscience.