Cummings, Damian M.; Milnerwood, Austen J.; Dallerac, Glenn M.; Waights, Verina; Brown, Jacki Y.; Vatsavayai, Sarat C.; Hirst, Mark C. and Murphy, Kerry P. S. J.
|DOI (Digital Object Identifier) Link:||http://dx.doi.org/doi:10.1093/hmg/ddl224|
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Predictive genetic testing for Huntington's disease (HD) has revealed early cognitive deficits in asymptomatic gene carriers, such as altered working memory, executive function and impaired recognition memory. The perirhinal cortex processes aspects of recognition memory and the underlying mechanism is believed to be long-term depression (LTD) of excitatory neurotransmission, the converse of long-term potentiation (LTP). We have used the R6/1 mouse model of HD to assess synaptic plasticity in the perirhinal cortex. We report here a progressive derailment of both LTD and short-term plasticity at perirhinal synapses. Layer II/III neurones gradually lose their ability to support LTD, show early nuclear localization of mutant huntingtin and display a progressive loss of membrane integrity (depolarization and loss of cell capacitance) accompanied by a reduction in the expression of D-1 and D-2 dopamine receptors visualized in layer I of the perirhinal cortex. Importantly, abnormalities in both short-term and long-term plasticity can be reversed by the introduction of a D-2 dopamine receptor agonist (Quinpirole), suggesting that alterations in dopaminergic signalling may underlie early cognitive dysfunction in HD.
|Item Type:||Journal Article|
|Keywords:||long-term depression; neuronal intranuclear inclusions; striatal spiny neurons; transgenic mice; mutant huntingtin; r6/2 mouse; corticostriatal synapses; degenerative changes; cognitive deficits; perirhinal cortex|
|Academic Unit/Department:||Health and Social Care > Nursing
Science > Life, Health and Chemical Sciences
|Depositing User:||Astrid Peterkin|
|Date Deposited:||02 Feb 2007|
|Last Modified:||02 Dec 2010 19:57|
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