title: Deficits in experience-dependent cortical plasticity and sensory-discrimination learning in presymptomatic Huntington's disease mice.
abstract: Huntington's disease (HD) is one of a group of neurodegenerative diseases caused by an expanded trinucleotide (CAG) repeat coding for an extended polyglutamine tract. The disease is inherited in an autosomal dominant manner, with onset of motor, cognitive, and psychiatric symptoms typically occurring in midlife, followed by unremitting progression and eventual death. We report here that motor presymptomatic R6/1 HD mice show a severe impairment of somatosensory-discrimination learning ability in a behavioral task that depends heavily on the barrel cortex. In parallel, there are deficits in barrel-cortex plasticity after a somatosensory whisker-deprivation paradigm. The present study demonstrates deficits in neocortical plasticity correlated with a specific learning impairment involving the same neocortical area, a finding that provides new insight into the cellular basis of early cognitive deficits in HD.
authors.affiliation: University Laboratory of Physiology, University of Oxford, Oxford OX1 3PT, United Kingdom. nm1@physiol.ox.ac.uk
authors.forename: Nektarios K
authors.initials: NK
authors.lastname: Mazarakis
authors.forename: Anita
authors.initials: A
authors.lastname: Cybulska-Klosowicz
authors.forename: Helen
authors.initials: H
authors.lastname: Grote
authors.forename: Terence
authors.initials: T
authors.lastname: Pang
authors.forename: Anton
authors.initials: A
authors.lastname: Van Dellen
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Kossut
authors.forename: Colin
authors.initials: C
authors.lastname: Blakemore
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Hannan
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D001345:Autoradiography / Q000379:methods; D001522:Behavior, Animal; D003847:Deoxyglucose / Q000378:metabolism; D004193:Discrimination Learning / Q000502:physiology*; D004195:Disease Models, Animal; D005106:Exploratory Behavior / Q000502:physiology; D006816:Huntington Disease / Q000503:physiopathology*; D007859:Learning Disabilities / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology*; D011597:Psychomotor Performance / Q000502:physiology; D045442:Rotarod Performance Test / Q000379:methods; D012683:Sensory Deprivation / Q000502:physiology; D013003:Somatosensory Cortex / Q000473:pathology / Q000503:physiopathology*; D018709:Statistics, Nonparametric; D019680:Trinucleotide Repeat Expansion / Q000235:genetics; D014738:Vibrissae / Q000502:physiology
chemical_list: D003847:Deoxyglucose