Comparisons Of Corticostriatal And Thalamostriatal Projections In HD Mouse Models

Friday, October 28, 2011
Hall 1-2 (San Jose Convention Center)
Marlyn Davila , University of Houston-Downtown, Houston, TX
Anna Parievsky , Neuroscience Interdepartmental Program, University of California Los Angeles, Los Angeles, CA
Michael Levine, PhD , Intellectual and Developmental Disabilities Research Center, University of California Los Angeles, Los Angeles, CA
Huntington’s disease (HD) is an autosomal dominant disease caused by a CAG trinucleotide repeat expansion in exon 1 of the Huntington (HTT) gene. HD is characterized by motor dysfunction, progressive neurodegeneration, and cognitive decline. Although the exact mechanism of action of the HTT is not known, HTT is believed to play a role in endocytosis, exocytosis, and vesicle trafficking. The most obvious neuropathology seen in HD is cell death of striatal medium-sized spiny neurons (MSSNs); these cells serve as the primary input to the basal gangalia for motor control and execution.  HD studies have shown deterioration in both the cortex and thalamus, which are the two major inputs into the striatum. The goal of this project is to compare changes in corticostriatal and thalamostriatal projections in HD versus wildtype mice.  We used electrophysiological techniques to record responses of striatal MSSNs evoked by selective stimulation of thalamostriatal or corticostriatal projections with the use of optogenetics. We plan to evaluate the changes between the two projections in HD compared to wildtype mice by measuring amplitude of evoked responses and rundown of responses evoked by continuous stimulation. We will also compare the kinetics of the evoked responses by measuring the rise time, decay time, and half width of the peaks from the stimulated responses. We hypothesize that the changes in HD mice will be more prominent in corticostriatal versus thalamostriatal evoked responses. So far analysis of preliminary results supports the hypothesis showing greater changes in corticostriatal projections in HD mice than thalamostriatal.