Deficits in experience-dependent cortical plasticity and sensory-discrimination learning in presymptomatic Huntington's disease mice.
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.
Mazarakis
Nektarios K
NK
University Laboratory of Physiology, University of Oxford, Oxford OX1 3PT, United Kingdom. nm1@physiol.ox.ac.uk
Cybulska-Klosowicz
Anita
A
Grote
Helen
H
Pang
Terence
T
Van Dellen
Anton
A
Kossut
Malgorzata
M
Blakemore
Colin
C
Hannan
Anthony J
AJ
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
D003847:Deoxyglucose