title: Memory-Relevant Mushroom Body Output Synapses Are Cholinergic.
abstract: Memories are stored in the fan-out fan-in neural architectures of the mammalian cerebellum and hippocampus and the insect mushroom bodies. However, whereas key plasticity occurs at glutamatergic synapses in mammals, the neurochemistry of the memory-storing mushroom body Kenyon cell output synapses is unknown. Here we demonstrate a role for acetylcholine (ACh) in Drosophila. Kenyon cells express the ACh-processing proteins ChAT and VAChT, and reducing their expression impairs learned olfactory-driven behavior. Local ACh application, or direct Kenyon cell activation, evokes activity in mushroom body output neurons (MBONs). MBON activation depends on VAChT expression in Kenyon cells and is blocked by ACh receptor antagonism. Furthermore, reducing nicotinic ACh receptor subunit expression in MBONs compromises odor-evoked activation and redirects odor-driven behavior. Lastly, peptidergic corelease enhances ACh-evoked responses in MBONs, suggesting an interaction between the fast- and slow-acting transmitters. Therefore, olfactory memories in Drosophila are likely stored as plasticity of cholinergic synapses.
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Oliver
authors.initials: O
authors.lastname: Barnstedt
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK. Electronic address: david.owald@charite.de.
authors.forename: David
authors.initials: D
authors.lastname: Owald
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Johannes
authors.initials: J
authors.lastname: Felsenberg
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: Brain
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: John-Paul
authors.initials: JP
authors.lastname: Moszynski
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK.
authors.forename: Clifford B
authors.initials: CB
authors.lastname: Talbot
authors.affiliation: Department of Neurobiology, UMass Medical School, Worcester, MA 01605, USA.
authors.forename: Paola N
authors.initials: PN
authors.lastname: Perrat
authors.affiliation: Centre for Neural Circuits and Behaviour, The University of Oxford, Tinsley Building, Mansfield Road, Oxford OX1 3SR, UK. Electronic address: scott.waddell@cncb.ox.ac.uk.
authors.forename: Scott
authors.initials: S
authors.lastname: Waddell
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D002795:Choline O-Acetyltransferase / Q000235:genetics / Q000378:metabolism; D018678:Cholinergic Agents / Q000378:metabolism* / Q000494:pharmacology; D003214:Conditioning, Classical / Q000187:drug effects / Q000502:physiology; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D005968:Glutamate Decarboxylase / Q000235:genetics / Q000378:metabolism; D008568:Memory / Q000502:physiology*; D024521:Mushroom Bodies / Q000166:cytology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D034622:RNA Interference / Q000502:physiology; D013569:Synapses / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D050494:Vesicular Acetylcholine Transport Proteins / Q000378:metabolism; D050496:Vesicular Glutamate Transport Proteins / Q000235:genetics / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018678:Cholinergic Agents; D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D014157:Transcription Factors; C493462:VAChT protein, Drosophila; D050494:Vesicular Acetylcholine Transport Proteins; D050496:Vesicular Glutamate Transport Proteins; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D002795:Choline O-Acetyltransferase; D005968:Glutamate Decarboxylase; D002118:Calcium