Aberrant cortical synaptic plasticity and dopaminergic dysfunction in a mouse model of huntington's disease

• DOI: 10.1093/hmg/ddl224
• Publication Date: 2006-08-12T00:13:33Z
• Authors: Damian M. Cummings; Austen J. Milnerwood; Glenn M. Dallérac; Verina Waights; Jacki Y. Brown; Sarat C. Vatsavayai; Mark C. Hirst; Kerry P.S.J. Murphy
• Keywords: Perirhinal cortex

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 memory the underlying mechanism is believed to be long-term depression (LTD) excitatory neurotransmission, converse potentiation (LTP). We have used R6/1 mouse model HD assess synaptic plasticity cortex. report here a progressive derailment both LTD short-term at synapses. Layer II/III neurones gradually lose their ability support LTD, show nuclear localization mutant huntingtin display loss membrane integrity (depolarization cell capacitance) accompanied by reduction expression D1 D2 dopamine receptors visualized layer I Importantly, abnormalities can reversed introduction receptor agonist (Quinpirole), suggesting that alterations dopaminergic signalling may underlie dysfunction HD.