RRC ID 28873
著者 Cavaliere S, Malik BR, Hodge JJ.
タイトル KCNQ channels regulate age-related memory impairment.
ジャーナル PLoS One
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.
巻・号 8(4)
ページ e62445
公開日 2013-4-30
DOI 10.1371/journal.pone.0062445
PII PONE-D-13-03915
PMID 23638087
PMC PMC3640075
MeSH Aging Animals Drosophila / drug effects Drosophila / genetics Drosophila / physiology* Ethanol / adverse effects Gene Expression Regulation KCNQ Potassium Channels / genetics* KCNQ Potassium Channels / metabolism* Memory* / drug effects Memory, Short-Term Mushroom Bodies / cytology Mushroom Bodies / metabolism Mutation* Neurons / cytology Neurons / metabolism Signal Transduction
IF 2.74
引用数 13
WOS 分野 NEUROSCIENCES
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