Time course of choice reaction time deficits in the Hdh(Q92) knock-in mouse model of Huntington's disease in the operant serial implicit learning task (SILT).
A range of transgenic and knock-in mouse models of Huntington's disease have been created since identification in 1993 of the disease mutation in the HD gene. Knock-in models that express the full-length mutant protein tend to exhibit less severe behavioural deficits than transgenic models and so require more sensitive tasks in order to reveal impairments. To achieve this, we therefore used a Serial Implicit Learning Task (SILT), which measures serial reaction times to visual stimuli, requiring detection and responding in both predictable and unpredictable locations in the 9-hole operant chamber. We have previously reported that knock-in Hdh(Q92/Q92) mice exhibit a modest impairment in learning the SILT tasks at 4 months of age, prior to the formation of overt neuronal nuclear inclusions. In the present study we have explored the time course of the development of impairments from 5 to 14 months of age. The deficit previously found in accuracy and reaction time was present at all ages examined in these Hdh(Q92/Q92) mice; the deficit was not progressive, and did not correlate with the evolution of neuronal nuclear inclusions.
Trueman
Rebecca C
RC
School of Biosciences, Cardiff University, Cardiff, Wales, UK. truemanrc@cardiff.ac.uk
Brooks
Simon P
SP
Jones
Lesley
L
Dunnett
Stephen B
SB
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D002755:Choice Behavior / Q000502:physiology*; D003216:Conditioning, Operant / Q000502:physiology; D004195:Disease Models, Animal; D005260:Female; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D010775:Photic Stimulation; D011337:Probability Learning; D011597:Psychomotor Performance / Q000502:physiology*; D011930:Reaction Time / Q000502:physiology*; D012691:Serial Learning / Q000502:physiology*; D013045:Species Specificity
C506812:Htt protein, mouse; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins