Subtle but progressive cognitive deficits in the female tgHD hemizygote rat as demonstrated by operant SILT performance.
In accordance with the genetic nature of Huntington's disease (HD), transgenic and knock-in mouse models have been developed that have sought to recapitulate the key features of the human condition. To date, only a single rat model has been developed, the tgHD rat that carries 51 CAG repeats. The tgHD rat has many of the anatomical and behavioural characteristics of HD, including cognitive, emotional and motor abnormalities. To characterize this model further, hemizygous tgHD rats were tested on an operant serial implicit learning task (SILT), to determine whether these animals have an implicit learning deficit as reported in HD patients. The SILT utilises a predictable two-stage sequence of responding to two consecutive stimuli (S1 and S2) as a probe of implicit learning, embedded amongst many randomly presented two-stage sequences. The results suggest that the hemizygous tgHD rats have a mild but progressive cognitive deficit that is attentional in nature. Longitudinal responding to the S1 stimuli demonstrated deficits that progressed over time for both accuracy and reaction time measures, whereas responses to S2 stimuli were mild and stable over time. Whilst a significant effect of predictability over time was identified, analyses of the final time point alone, failed to demonstrate between group differences in their ability to utilise the predictable information at this time point, when differences between the groups should be at their most pronounced. The results suggest that the hemizygous tgHD rats have mild cognitive deficits that are attentional in nature, but no implicit learning deficit.
Brooks
Simon
S
Brain Repair Group, School of Biosciences, Cardiff University, Museum Avenue, Cardiff CF10 3US, Wales, UK. BrooksSP@cardiff.ac.uk
Fielding
Steven
S
Döbrössy
Màtè
M
von Hörsten
Stephan
S
Dunnett
Stephen
S
D000818:Animals; D003071:Cognition; D003072:Cognition Disorders / Q000235:genetics* / Q000523:psychology; D003216:Conditioning, Operant; D004195:Disease Models, Animal; D005260:Female; D005838:Genotype; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000235:genetics / Q000523:psychology; D007859:Learning Disabilities / Q000235:genetics; D008137:Longitudinal Studies; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics*; D051381:Rats; D055647:Rats, Transgenic; D011930:Reaction Time
C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins