Abnormal cortical synaptic plasticity in a mouse model of Huntington's disease.
Huntington's disease is a fatal neurodegenerative disorder characterised by a progressive motor, psychiatric and cognitive decline and associated with a marked loss of neurons in the cortex and striatum of affected individuals. The disease is inherited in an autosomal dominant fashion and is caused by a trinucleotide (CAG) repeat expansion in the gene encoding the protein huntingtin. Predictive genetic testing has revealed early cognitive deficits in asymptomatic gene carriers such as altered working memory, executive function and recognition memory. The perirhinal cortex is believed to process aspects of recognition memory. Evidence from primate studies suggests that decrements in neuronal firing within this cortical region encode recognition memory and that the underlying mechanism is an activity-dependent 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. This mouse model provides an ideal tool for investigating early and progressive changes in synaptic function in HD. We report here that LTD at perirhinal synapses is markedly reduced in R6/1 mice. We also provide evidence to suggest that a reduction in dopamine D2 receptor signalling may be implicated.
Cummings
Damian M
DM
Huntington's Disease Research Forum, Department of Biological Sciences, The Open University, Walton Hall, Milton Keynes, UK.
Milnerwood
Austen J
AJ
Dallérac
Glenn M
GM
Vatsavayai
Sarat C
SC
Hirst
Mark C
MC
Murphy
Kerry P S J
KP
D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology*; D004195:Disease Models, Animal; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006816:Huntington Disease / Q000150:complications / Q000503:physiopathology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008569:Memory Disorders / Q000209:etiology; D051379:Mice; D008839:Microelectrodes; D009924:Organ Culture Techniques; D013569:Synapses / Q000473:pathology