2008 Eighth Annual Beckman Scholars Symposium
Saturday Poster Session - July 29, 2006

Huntington’s Disease (HD) is an autosomal dominant degenerative disorder of the central nervous system, particularly the basal ganglia. The basal ganglia are a subset of nuclei that regulate movement. The primary input center of the basal ganglia is the striatum and the main output nucleus is the substantia nigra reticulata (SNr). The SNr provides inhibitory modulation to other regions of the brain. Recently, the effects of the striatum on the SNr have been the topic of considerable debate. The conventional model of the basal ganglia suggests that a direct striatonigral pathway inhibits the SNr while an indirect pathway excites it. Several lines of evidence now indicate that the conventional model cannot account for some of the subtleties of striatonigral communication. HD causes considerable changes in the striatum; therefore, HD model organisms provide an excellent opportunity to elucidate the function of the basal ganglia. Specifically, such research can clarify the debate surrounding the conventional model because this model makes testable prediction about the HD phenotype. Previous work suggests that the area of the striatum responsible for inhibiting SNr is over-active in HD while the area responsible for excitation is under-active. In the context of the conventional model, such pathological changes could lead to over-inhibition of SNr resulting in the motor effects of HD. In the current study average neuronal firing patterns are observed in free-behaving HD transgenic mice using microwire electrodes. Single units are isolated using autocorrelation and principle component analysis along with qualitative analysis of waveform and signal to noise ratio. Data gathered from 33 neurons confirm the primary hypothesis that the SNr is under-active in HD mice. An independent-samples t-test shows that this effect is significant (p=.020). These data provide a possible explanation for the motor symptoms of HD. Moreover, our findings are consistent with the conventional model of striatonigral communication suggesting that this model should be modified but not discarded.