title: Drosophila SLC22A Transporter Is a Memory Suppressor Gene that Influences Cholinergic Neurotransmission to the Mushroom Bodies.
abstract: The mechanisms that constrain memory formation are of special interest because they provide insights into the brain's memory management systems and potential avenues for correcting cognitive disorders. RNAi knockdown in the Drosophila mushroom body neurons (MBn) of a newly discovered memory suppressor gene, Solute Carrier DmSLC22A, a member of the organic cation transporter family, enhances olfactory memory expression, while overexpression inhibits it. The protein localizes to the dendrites of the MBn, surrounding the presynaptic terminals of cholinergic afferent fibers from projection neurons (Pn). Cell-based expression assays show that this plasma membrane protein transports cholinergic compounds with the highest affinity among several in vitro substrates. Feeding flies choline or inhibiting acetylcholinesterase in Pn enhances memory, an effect blocked by overexpression of the transporter in the MBn. The data argue that DmSLC22A is a memory suppressor protein that limits memory formation by helping to terminate cholinergic neurotransmission at the Pn:MBn synapse.
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
authors.forename: Yunchao
authors.initials: Y
authors.lastname: Gai
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
authors.forename: Ze
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA.
authors.forename: Isaac
authors.initials: I
authors.lastname: Cervantes-Sandoval
authors.affiliation: Department of Neuroscience, The Scripps Research Institute Florida, Jupiter, FL 33458, USA. Electronic address: rdavis@scripps.edu.
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Davis
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D002799:Cholinergic Fibers / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000502:physiology*; D016153:Genes, Suppressor / Q000502:physiology; D008568:Memory / Q000502:physiology*; D024521:Mushroom Bodies / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D002352:Carrier Proteins; D029721:Drosophila Proteins; D027701:Organic Cation Transport Proteins; C000621997:SLC22A protein, Drosophila