Behavioral and In Vivo Electrophysiological Evidence for Presymptomatic Alteration of Prefrontostriatal Processing in the Transgenic Rat Model for Huntington Disease

摘要: Cognitive decline precedes motor symptoms in Huntington disease (HD). A transgenic rat model for HD carrying only 51 CAG repeats recapitulates the late-onset phenotype. Here, we assessed prefrontostriatal function this through both behavioral and electrophysiological assays. Behavioral examination consisted a temporal bisection task within supra-second range (2 vs.8 s), which is thought to involve networks. In two independent experiments, analysis revealed poorer sensitivity as early 4 months of age, well before detection overt deficits. At later symptomatic animals were impaired their discriminative behavior. vivo recording field potentials dorsomedial striatum evoked by stimulation prelimbic cortex studied 4- 5-month-old rats. Input/output curves, paired-pulse function, plasticity induced theta-burst (TBS) assessed. Results showed an altered plasticity, with higher facilitation, enhanced short-term depression, stronger long-term potentiation after TBS homozygous from heterozygous mostly fell between wild-type Our results suggest that normal circuits may be necessary reliable precise timing Furthermore, present study provides first evidence presymptomatic alteration processing animal suggests earliest cognitive dysfunction HD.