A Pair of Inhibitory Neurons Are Required to Sustain Labile Memory in the Drosophila Mushroom Body

Labile memory is thought to be held in the brain as persistent neural network activity. However, it is not known how biologically relevant memory circuits are organized and operate. Labile and persistent appetitive memory in Drosophila requires output after training from the α'β' subset of mushroom body (MB) neurons and from a pair of modulatory dorsal paired medial (DPM) neurons. DPM neurons innervate the entire MB lobe region and appear to be pre- and postsynaptic to the MB, consistent with a recurrent network model. Here we identify a role after training for synaptic output from the GABAergic anterior paired lateral (APL) neurons. Blocking synaptic output from APL neurons after training disrupts labile memory but does not affect long-term memory. APL neurons contact DPM neurons most densely in the α'β' lobes, although their processes are intertwined and contact throughout all of the lobes. Furthermore, APL contacts MB neurons in the α' lobe but makes little direct contact with those in the distal α lobe. We propose that APL neurons provide widespread inhibition to stabilize and maintain synaptic specificity of a labile memory trace in a recurrent DPM and MB α'β' neuron circuit.

[1]  Liang Liang,et al.  The Q System: A Repressible Binary System for Transgene Expression, Lineage Tracing, and Mosaic Analysis , 2010, Cell.

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

[3]  Stephan J. Sigrist,et al.  Bruchpilot, a Protein with Homology to ELKS/CAST, Is Required for Structural Integrity and Function of Synaptic Active Zones in Drosophila , 2006, Neuron.

[4]  P. Goldman-Rakic.  Cellular basis of working memory , 1995, Neuron.

[5]  Michael Scholz,et al.  New methods for the computer-assisted 3-D reconstruction of neurons from confocal image stacks , 2004, NeuroImage.

[6]  R. Davis,et al.  Tripartite mushroom body architecture revealed by antigenic markers. , 1998, Learning & memory.

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

[8]  Raju Tomer,et al.  Profiling by Image Registration Reveals Common Origin of Annelid Mushroom Bodies and Vertebrate Pallium , 2010, Cell.

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

[10]  Kei Ito,et al.  Gamma‐aminobutyric acid (GABA)‐mediated neural connections in the Drosophila antennal lobe , 2009, The Journal of comparative neurology.

[11]  J. Bassett,et al.  Persistent neural activity in head direction cells. , 2003, Cerebral cortex.

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

[13]  Andreas S. Thum,et al.  Behavioral/systems/cognitive Multiple Memory Traces for Olfactory Reward Learning in Drosophila Materials and Methods , 2022 .

[14]  R. Douglas,et al.  Recurrent neuronal circuits in the neocortex , 2007, Current Biology.

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

[16]  Xiao-Jing Wang.  Synaptic reverberation underlying mnemonic persistent activity , 2001, Trends in Neurosciences.

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

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

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

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

[21]  W. Quinn,et al.  Radish, a Drosophila mutant deficient in consolidated memory. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

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

[23]  Ronald L. Davis,et al.  Drosophila alpha/beta mushroom body neurons form a branch-specific, long-term cellular memory trace after spaced olfactory conditioning. , 2006, Neuron.

[24]  Kei Ito,et al.  Neuronal assemblies of the Drosophila mushroom body , 2008, The Journal of comparative neurology.

[25]  Michael T. Mader,et al.  The Drosophila Standard Brain , 2002, Current Biology.

[26]  A. Compte.  Computational and in vitro studies of persistent activity: Edging towards cellular and synaptic mechanisms of working memory , 2006, Neuroscience.

[27]  L. Abbott,et al.  Divisive inhibition in recurrent networks , 2000, Network.

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

[29]  Liqun Luo,et al.  Mosaic Analysis with a Repressible Cell Marker for Studies of Gene Function in Neuronal Morphogenesis , 1999, Neuron.

[30]  A. Chiang,et al.  Aging Specifically Impairs amnesiac-Dependent Memory in Drosophila , 2003, Neuron.

[31]  M. Heisenberg.  Mushroom body memoir: from maps to models , 2003, Nature Reviews Neuroscience.

[32]  S. Waddell,et al.  Diverse Odor-Conditioned Memories Require Uniquely Timed Dorsal Paired Medial Neuron Output , 2004, Neuron.

[33]  Sen-Lin Lai,et al.  Genetic mosaic with dual binary transcriptional systems in Drosophila , 2006, Nature Neuroscience.

[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]  R. Davis,et al.  The Role of Drosophila Mushroom Body Signaling in Olfactory Memory , 2001, Science.

[36]  S. Waddell,et al.  Drosophila olfactory memory: single genes to complex neural circuits , 2007, Nature Reviews Neuroscience.

[37]  H. Seung,et al.  In vivo intracellular recording and perturbation of persistent activity in a neural integrator , 2001, Nature Neuroscience.

[38]  Michael J. Krashes,et al.  Drosophila Dorsal Paired Medial Neurons Provide a General Mechanism for Memory Consolidation , 2006, Current Biology.

[39]  Ronald L. Davis,et al.  Drosophila α/β Mushroom Body Neurons Form a Branch-Specific, Long-Term Cellular Memory Trace after Spaced Olfactory Conditioning , 2006, Neuron.

[40]  M. Low,et al.  Disruption of neurotransmission in Drosophila mushroom body blocks retrieval but not acquisition of memory , 2022 .

[41]  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.

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