Huntington's disease (HD) is caused by an expanded CAG repeat leading to the synthesis of an aberrant protein and to the formation of polyglutamine (polyQ)-containing inclusions and aggregates. Limited information is available concerning the association of neuropathological markers with the development of behavioral markers in HD. Using a previously generated transgenic rat model of HD (tgHD rat), we performed association studies on the time-course of behavioral symptoms (motor function, learning, anxiety) and the appearance of striatal atrophy, 1C2 immunopositive aggregates and polyQ recruitment sites, a precursor to these aggregates. At the age of 1 month, tgHD rats exhibited reduced anxiety and improved motor performance, while at 6 months motor impairments and at 9 months cognitive decline occurred. In contrast, polyQ recruitment sites appeared at around 6-9 months of age, indicating that HD-like behavioral markers preceded the appearance of currently detectable neuropathological markers. Interestingly, numerous punctate sites containing polyQ aggregates were also seen in areas receiving afferents from the densely recruiting regions suggesting either transport of recruitment-competent aggregates to terminal projections where initially 1C2 positive aggregates were formed or different internal properties of neurons in different regions. Furthermore, striatal atrophy was observed at the age of 12 months. Taken together, our findings support the hypothesis of a dynamic process leading to region- and age-specific polyQ recruitment and aggregation. The dissociation of onset between behavioral and neuropathological markers is suggestive of as yet undetected processes, which contribute to the early phenotype of these HD transgenic rats.

Degenerative changes of photoreceptors and pigment epithelium shown here prior to apoptotic loss of photoreceptors may contribute to functional alterations reported in diabetic human patients and different animal models, thus may serve as a potential model for testing the efficacy of neuroprotective agents in diabetes.

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Converging evidence shows that interaction of digit-specific input, which is required to form global tactile percepts, begins as early as area 3b in the primary somatosensory cortex with the involvement of intrinsic lateral connections. How tactile processing is further elaborated in area 1, the next stage of the somatosensory cortical hierarchy, is less understood. This question was investigated by studying the tangential distribution of intrinsic and interareal connections of finger representations of area 1. Retrogradely labeled cell densities and anterogradely labeled fibers and terminal patches were plotted and quantified with respect to the hand representation by combining tract tracing with electrophysiological mapping and intrinsic signal optical imaging in somatosensory areas. Intrinsic connections of distal finger pad representations of area 1 spanned the representation of multiple digits indicating strong cross-digit connectivity. Area 1 distal finger pad regions also established high-density connections with homotopic regions of areas 3b and 2. Although similar to area 3b, connections of area 1 distributed more widely and covered a larger somatotopic representation including more proximal parts of the finger representations. The lateral connectivity pattern of area 1 is a suitable anatomical substrate of the emergence of multifinger receptive fields, complex feature selectivity, and invariant stimulus properties of the neurons.