title: Behavioral and in vivo electrophysiological evidence for presymptomatic alteration of prefrontostriatal processing in the transgenic rat model for huntington disease.
abstract: Cognitive decline precedes motor symptoms in Huntington disease (HD). A transgenic rat model for HD carrying only 51 CAG repeats recapitulates the late-onset HD phenotype. Here, we assessed prefrontostriatal function in this model through both behavioral and electrophysiological assays. Behavioral examination consisted in a temporal bisection task within a supra-second range (2 vs.8 s), which is thought to involve prefrontostriatal networks. In two independent experiments, the behavioral analysis revealed poorer temporal sensitivity as early as 4 months of age, well before detection of overt motor deficits. At a later symptomatic age, animals were impaired in their temporal discriminative behavior. In vivo recording of field potentials in the dorsomedial striatum evoked by stimulation of the prelimbic cortex were studied in 4- to 5-month-old rats. Input/output curves, paired-pulse function, and plasticity induced by theta-burst stimulation (TBS) were assessed. Results showed an altered plasticity, with higher paired-pulse facilitation, enhanced short-term depression, as well as stronger long-term potentiation after TBS in homozygous transgenic rats. Results from the heterozygous animals mostly fell between wild-type and homozygous transgenic rats. Our results suggest that normal plasticity in prefrontostriatal circuits may be necessary for reliable and precise timing behavior. Furthermore, the present study provides the first behavioral and electrophysiological evidence of a presymptomatic alteration of prefrontostriatal processing in an animal model for Huntington disease and suggests that supra-second timing may be the earliest cognitive dysfunction in HD.
authors.affiliation: Université Paris-Sud, Centre de Neurosciences Paris-Sud, Unité Mixte de Recherche 8195, F-91405 Orsay, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Höhn
authors.forename: Glenn
authors.initials: G
authors.lastname: Dallérac
authors.forename: Alexis
authors.initials: A
authors.lastname: Faure
authors.forename: Yvonne K
authors.initials: YK
authors.lastname: Urbach
authors.forename: Huu Phuc
authors.initials: HP
authors.lastname: Nguyen
authors.forename: Olaf
authors.initials: O
authors.lastname: Riess
authors.forename: Stephan
authors.initials: S
authors.lastname: von Hörsten
authors.forename: Pascale
authors.initials: P
authors.lastname: Le Blanc
authors.forename: Nathalie
authors.initials: N
authors.lastname: Desvignes
authors.forename: Nicole
authors.initials: N
authors.lastname: El Massioui
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Brown
authors.forename: Valerie
authors.initials: V
authors.lastname: Doyère
mesh_terms: D000161:Acoustic Stimulation / Q000009:adverse effects; D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D001522:Behavior, Animal / Q000502:physiology*; D003342:Corpus Striatum / Q000503:physiopathology*; D004192:Discrimination, Psychological / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004569:Electroencephalography / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D005838:Genotype; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D007266:Inhibition, Psychological; D008137:Longitudinal Studies; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009483:Neuropsychological Tests; D009687:Nuclear Proteins / Q000235:genetics; D010852:Picrotoxin / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000503:physiopathology*; D011597:Psychomotor Performance / Q000502:physiology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000235:genetics; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics; D013570:Synaptic Membranes / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D019680:Trinucleotide Repeat Expansion / Q000235:genetics
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D010852:Picrotoxin; D011810:Quinoxalines; C499524:Htt protein, rat; C056723:FG 9041