title: KCNQ channels regulate age-related memory impairment.
abstract: In humans KCNQ2/3 heteromeric channels form an M-current that acts as a brake on neuronal excitability, with mutations causing a form of epilepsy. The M-current has been shown to be a key regulator of neuronal plasticity underlying associative memory and ethanol response in mammals. Previous work has shown that many of the molecules and plasticity mechanisms underlying changes in alcohol behaviour and addiction are shared with those of memory. We show that the single KCNQ channel in Drosophila (dKCNQ) when mutated show decrements in associative short- and long-term memory, with KCNQ function in the mushroom body α/βneurons being required for short-term memory. Ethanol disrupts memory in wildtype flies, but not in a KCNQ null mutant background suggesting KCNQ maybe a direct target of ethanol, the blockade of which interferes with the plasticity machinery required for memory formation. We show that as in humans, Drosophila display age-related memory impairment with the KCNQ mutant memory defect mimicking the effect of age on memory. Expression of KCNQ normally decreases in aging brains and KCNQ overexpression in the mushroom body neurons of KCNQ mutants restores age-related memory impairment. Therefore KCNQ is a central plasticity molecule that regulates age dependent memory impairment.
authors: School of Physiology and Pharmacology, University of Bristol, Bristol, Avon, United Kingdom.
authors: Sonia
authors: S
authors: Cavaliere
authors: Bilal R
authors: BR
authors: Malik
authors: James J L
authors: JJ
authors: Hodge
mesh_terms: D000375:Aging; D000818:Animals; D004330:Drosophila / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000431:Ethanol / Q000009:adverse effects; D005786:Gene Expression Regulation; D051656:KCNQ Potassium Channels / Q000235:genetics* / Q000378:metabolism*; D008568:Memory / Q000187:drug effects; D008570:Memory, Short-Term; D024521:Mushroom Bodies / Q000166:cytology / Q000378:metabolism; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D051656:KCNQ Potassium Channels; D000431:Ethanol
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