Reward signal in a recurrent circuit drives appetitive long-term memory formation

Dopamine signals reward in animal brains. A single presentation of a sugar reward to Drosophila activates distinct subsets of dopamine neurons that independently induce short- and long-term olfactory memories (STM and LTM, respectively). In this study, we show that a recurrent reward circuit underlies the formation and consolidation of LTM. This feedback circuit is composed of a single class of reward-signaling dopamine neurons (PAM-α1) projecting to a restricted region of the mushroom body (MB), and a specific MB output cell type, MBON-α1, whose dendrites arborize that same MB compartment. Both MBON-α1 and PAM-α1 neurons are required during the acquisition and consolidation of appetitive LTM. MBON-α1 additionally mediates the retrieval of LTM, which is dependent on the dopamine receptor signaling in the MB α/β neurons. Our results suggest that a reward signal transforms a nascent memory trace into a stable LTM using a feedback circuit at the cost of memory specificity. DOI: http://dx.doi.org/10.7554/eLife.10719.001

[1]  Hyoung F. Kim,et al.  Distinct Basal Ganglia Circuits Controlling Behaviors Guided by Flexible and Stable Values , 2013, Neuron.

[2]  Ann-Shyn Chiang,et al.  Drosophila ORB protein in two mushroom body output neurons is necessary for long-term memory formation , 2013, Proceedings of the National Academy of Sciences.

[3]  Robert A. A. Campbell,et al.  Cellular-Resolution Population Imaging Reveals Robust Sparse Coding in the Drosophila Mushroom Body , 2011, The Journal of Neuroscience.

[4]  Y. Zhong,et al.  A Permissive Role of Mushroom Body α/β Core Neurons in Long-Term Memory Consolidation in Drosophila , 2012, Current Biology.

[5]  Charles R. Gerfen,et al.  High-performance probes for light and electron microscopy , 2015, Nature Methods.

[6]  Hans Liljenström,et al.  Neural Stability and Flexibility: A Computational Approach , 2003, Neuropsychopharmacology.

[7]  Alcino J. Silva,et al.  Memory for context becomes less specific with time. , 2007, Learning & memory.

[8]  G. Rubin,et al.  The neuronal architecture of the mushroom body provides a logic for associative learning , 2014, eLife.

[9]  Y. Zhong,et al.  Requirement of the combination of mushroom body γ lobe and α/β lobes for the retrieval of both aversive and appetitive early memories in Drosophila. , 2013, Learning & memory.

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

[11]  I. Izquierdo,et al.  Dopamine Controls Persistence of Long-Term Memory Storage , 2009, Science.

[12]  Daryl M. Gohl,et al.  Layered reward signaling through octopamine and dopamine in Drosophila , 2012, Nature.

[13]  T. Carew,et al.  Pattern and predictability in memory formation: From molecular mechanisms to clinical relevance , 2013, Neurobiology of Learning and Memory.

[14]  Yoshinori Aso,et al.  Distinct dopamine neurons mediate reward signals for short- and long-term memories , 2014, Proceedings of the National Academy of Sciences.

[15]  Scott Waddell,et al.  Drosophila Learn Opposing Components of a Compound Food Stimulus , 2014, Current Biology.

[16]  M. Heisenberg,et al.  An engram found? Evaluating the evidence from fruit flies , 2004, Current Opinion in Neurobiology.

[17]  J. Lisman,et al.  The Hippocampal-VTA Loop: Controlling the Entry of Information into Long-Term Memory , 2005, Neuron.

[18]  T. Préat,et al.  Parametric and genetic analysis of Drosophila appetitive long‐term memory and sugar motivation , 2009, Genes, brain, and behavior.

[19]  Ann-Shyn Chiang,et al.  NMDA Receptors Mediate Olfactory Learning and Memory in Drosophila , 2005, Current Biology.

[20]  S. Waddell,et al.  Remembering Nutrient Quality of Sugar in Drosophila , 2011, Current Biology.

[21]  Frederic Mery,et al.  A Cost of Long-Term Memory in Drosophila , 2005, Science.

[22]  Wanhe Li,et al.  Gamma Neurons Mediate Dopaminergic Input during Aversive Olfactory Memory Formation in Drosophila , 2012, Current Biology.

[23]  G. Nagel,et al.  Light-Induced Activation of Distinct Modulatory Neurons Triggers Appetitive or Aversive Learning in Drosophila Larvae , 2006, Current Biology.

[24]  W. Schultz.  Updating dopamine reward signals , 2013, Current Opinion in Neurobiology.

[25]  T. Préat,et al.  To Favor Survival Under Food Shortage, the Brain Disables Costly Memory , 2013, Science.

[26]  Clint J. Perry,et al.  Neural mechanisms of reward in insects. , 2013, Annual review of entomology.

[27]  Bruce D. Gelb,et al.  The Phosphatase SHP2 Regulates the Spacing Effect for Long-Term Memory Induction , 2009, Cell.

[28]  S. Tomchik,et al.  Dopaminergic Modulation of cAMP Drives Nonlinear Plasticity across the Drosophila Mushroom Body Lobes , 2014, Current Biology.

[29]  E. Buchner,et al.  The Wuerzburg Hybridoma Library against Drosophila Brain , 2009, Journal of neurogenetics.

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

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

[32]  G. Rubin,et al.  Shared mushroom body circuits underlie visual and olfactory memories in Drosophila , 2014, eLife.

[33]  A. Fiala,et al.  Punishment Prediction by Dopaminergic Neurons in Drosophila , 2005, Current Biology.

[34]  S. Waddell,et al.  Rapid Consolidation to a radish and Protein Synthesis-Dependent Long-Term Memory after Single-Session Appetitive Olfactory Conditioning in Drosophila , 2008, The Journal of Neuroscience.

[35]  Kristin Scott,et al.  Motor Control in a Drosophila Taste Circuit , 2009, Neuron.

[36]  K. Han,et al.  D1 Dopamine Receptor dDA1 Is Required in the Mushroom Body Neurons for Aversive and Appetitive Learning in Drosophila , 2007, The Journal of Neuroscience.

[37]  S. Waddell.  Reinforcement signalling in Drosophila; dopamine does it all after all , 2013, Current Opinion in Neurobiology.

[38]  Anne E Carpenter,et al.  Neuron-type specific signals for reward and punishment in the ventral tegmental area , 2011, Nature.

[39]  Julie H. Simpson,et al.  A GAL4-driver line resource for Drosophila neurobiology. , 2012, Cell reports.

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

[41]  M. Hammer.  An identified neuron mediates the unconditioned stimulus in associative olfactory learning in honeybees , 1993, Nature.

[42]  R. A. Koelling,et al.  Conditioned aversion to saccharin resulting from exposure to gamma radiation. , 1955, Science.

[43]  G. Audesirk,et al.  One-trial reward learning in the snail Lymnea stagnalis. , 1984, Journal of neurobiology.

[44]  Ronald L. Davis,et al.  System-Like Consolidation of Olfactory Memories in Drosophila , 2013, The Journal of Neuroscience.

[45]  B. Grünewald,et al.  Morphology of feedback neurons in the mushroom body of the honeybee, Apis mellifera , 1999, The Journal of comparative neurology.

[46]  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.

[47]  F. Jackson,et al.  Presynaptic Glutamic Acid Decarboxylase Is Required for Induction of the Postsynaptic Receptor Field at a Glutamatergic Synapse , 2000, Neuron.

[48]  Scott Waddell,et al.  Sweet Taste and Nutrient Value Subdivide Rewarding Dopaminergic Neurons in Drosophila , 2015, Current Biology.

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

[50]  G. Rubin,et al.  Refinement of Tools for Targeted Gene Expression in Drosophila , 2010, Genetics.

[51]  G. Rubin,et al.  A subset of dopamine neurons signals reward for odour memory in Drosophila , 2012, Nature.

[52]  Sachie K. Ogawa,et al.  Whole-Brain Mapping of Direct Inputs to Midbrain Dopamine Neurons , 2012, Neuron.

[53]  T. Schwarz,et al.  Synaptotagmins I and IV promote transmitter release independently of Ca2+ binding in the C2A domain , 2002, Nature.

[54]  Andrew C. Lin,et al.  Different Kenyon Cell Populations Drive Learned Approach and Avoidance in Drosophila , 2013, Neuron.

[55]  Hyoung F. Kim,et al.  Separate groups of dopamine neurons innervate caudate head and tail encoding flexible and stable value memories , 2014, Front. Neuroanat..

[56]  Wanhe Li,et al.  Imaging a Population Code for Odor Identity in the Drosophila Mushroom Body , 2013, The Journal of Neuroscience.

[57]  T. Préat,et al.  Delayed dopamine signaling of energy level builds appetitive long-term memory in Drosophila. , 2015, Cell reports.

[58]  Cori Bargmann,et al.  GFP Reconstitution Across Synaptic Partners (GRASP) Defines Cell Contacts and Synapses in Living Nervous Systems , 2008, Neuron.

[59]  W. Schultz,et al.  Importance of unpredictability for reward responses in primate dopamine neurons. , 1994, Journal of neurophysiology.

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

[61]  Thomas Preat,et al.  Parallel Processing of Appetitive Short- and Long-Term Memories In Drosophila , 2011, Current Biology.

[62]  G. Rubin,et al.  Mushroom body output neurons encode valence and guide memory-based action selection in Drosophila , 2014, eLife.

[63]  A Permissive Role of Mushroom Body alpha/beta Core Neurons in Long-Term Memory Consolidation in Drosophila , 2012 .

[64]  Martin Giurfa,et al.  The influence of training length on generalization of visual feature assemblies in honeybees , 2005, Behavioural Brain Research.

[65]  W. Abraham,et al.  Memory retention – the synaptic stability versus plasticity dilemma , 2005, Trends in Neurosciences.

[66]  Hiromu Tanimoto,et al.  Two pairs of mushroom body efferent neurons are required for appetitive long-term memory retrieval in Drosophila. , 2013, Cell reports.

[67]  B. Grünewald,et al.  Physiological properties and response modulations of mushroom body feedback neurons during olfactory learning in the honeybee, Apis mellifera , 1999, Journal of Comparative Physiology A.

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

[69]  Y. Zhong,et al.  The differential requirement of mushroom body α/β subdivisions in long-term memory retrieval in Drosophila , 2013, Protein & Cell.

[70]  P. Salvaterra,et al.  Analysis of choline acetyltransferase protein in temperature sensitive mutant flies using newly generated monoclonal antibody , 1996, Neuroscience Research.

[71]  Stefan R. Pulver,et al.  An internal thermal sensor controlling temperature preference in Drosophila , 2008, Nature.

[72]  P. Szepetowski.  NMDA Receptors , 2017, Methods in Molecular Biology.

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

[74]  Aljoscha Nern,et al.  Optimized tools for multicolor stochastic labeling reveal diverse stereotyped cell arrangements in the fly visual system , 2015, Proceedings of the National Academy of Sciences.

[75]  Aaron DiAntonio,et al.  Visualizing glutamatergic cell bodies and synapses in Drosophila larval and adult CNS , 2008, The Journal of comparative neurology.

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

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

[78]  F. Jackson,et al.  Drosophila GABAergic Systems: Sequence and Expression of Glutamic Acid Decarboxylase , 1990, Journal of neurochemistry.

[79]  Rachel I. Wilson,et al.  Glutamate is an inhibitory neurotransmitter in the Drosophila olfactory system , 2013, Proceedings of the National Academy of Sciences.

[80]  Norbert Perrimon,et al.  A genome-scale shRNA resource for transgenic RNAi in Drosophila , 2011, Nature Methods.