Abstract: In mouse models of Huntington’s disease (HD), synaptic alterations in the cerebral cortex and striatum are present before overt behavioral symptoms and cell death. Similarly, in HD patients, it is now widely accepted that early deficits can occur in the absence of neural atrophy or overt motor symptoms. In addition, hyperkinetic movements seen in early stages are followed by hypokinesis in the late stages, indicating that different processes may be affected. In mouse models, such behavioral alterations parallel complex biphasic changes in glutamate-mediated excitatory, γ-aminobutyric acid (GABA)-mediated inhibitory synaptic transmission and dopamine modulation in medium spiny neurons of the striatum as well as in cortical pyramidal neurons. The progressive electrophysiologic changes in synaptic communication that occur with disease stage in the cortical and basal ganglia circuits of HD mouse models strongly indicate that therapeutic interventions and strategies in human HD must be targeted to different mechanisms in each stage and to specific subclasses of neurons.
Publication Year: 2014
Publication Date: 2014-08-01
Language: en
Type: book
Indexed In: ['crossref']
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