| First Author | Martin LA | Year | 2010 |
| Journal | Eur J Neurosci | Volume | 31 |
| Issue | 3 | Pages | 544-55 |
| PubMed ID | 20105240 | Mgi Jnum | J:159466 |
| Mgi Id | MGI:4443146 | Doi | 10.1111/j.1460-9568.2009.07073.x |
| Citation | Martin LA, et al. (2010) Repetitive behavior and increased activity in mice with Purkinje cell loss: a model for understanding the role of cerebellar pathology in autism. Eur J Neurosci 31(3):544-55 |
| abstractText | Repetitive behaviors and hyperactivity are common features of developmental disorders, including autism. Neuropathology of the cerebellum is also a frequent occurrence in autism and other developmental disorders. Recent studies have indicated that cerebellar pathology may play a causal role in the generation of repetitive and hyperactive behaviors. In this study, we examined the relationship between cerebellar pathology and these behaviors in a mouse model of Purkinje cell loss. Specifically, we made aggregation chimeras between Lc/+ mutant embryos and +/+ embryos. Lc/+ mice lose 100% of their Purkinje cells postnatally due to a cell-intrinsic gain-of-function mutation. Through our histological examination, we demonstrated that Lc/+<-->+/+ chimeric mice have Purkinje cells ranging from zero to normal numbers. Our analysis of these chimeric cerebella confirmed previous studies on Purkinje cell lineage. The results of both open-field activity and hole-board exploration testing indicated negative relationships between Purkinje cell number and measures of activity and investigatory nose-poking. Additionally, in a progressive-ratio operant paradigm, we found that Lc/+ mice lever-pressed significantly less than +/+ controls, which led to significantly lower breakpoints in this group. In contrast, chimeric mice lever-pressed significantly more than controls and this repetitive lever-pressing behavior was significantly and negatively correlated with total Purkinje cell numbers. Although the performance of Lc/+ mice is probably related to their motor deficits, the significant relationships between Purkinje cell number and repetitive lever-pressing behavior as well as open-field activity measures provide support for a role of cerebellar pathology in generating repetitive behavior and increased activity in chimeric mice. |
