Huntington's disease (HD) is an inherited disorder characterized by early cognitive impairment followed by motor deficits and progressive dementia. A conditional model of the disease has been generated by using the tet-regulatable system. Mice expressing a truncated N-terminal mutated huntingtin showed neuronal inclusions and other characteristic neuropathologic changes together with progressive motor dysfunction that were reversed by blockade of the gene expression (Yamamoto A. et al, Cell. 101: 57-66, 2000). To further characterize the phenotype of these animals, we have explored whether the expression of the mutated protein changes hippocampal long-term potentiation (LTP), a leading model of learning and memory. LTP was induced through a theta-burst stimulation applied to the Schaeffer-collateral fibers in hippocampal slices. Field-excitatory postsynaptic responses were recorded from CA1 neurons. Mutant mice showed a decreased potentiation at 60 min. (122%, n=7 slices) compared to control animals (170%, n=8 slices). Thus, expression of a mutated huntingtin causes an impairment of synaptic plasticity that could underlie cognitive changes in the disease.
|Issue number||4 SUPPL.|
|Publication status||Published - 2000|
ASJC Scopus subject areas
- Clinical Neurology