title: Altered information processing in the prefrontal cortex of Huntington's disease mouse models.
abstract: Understanding cortical information processing in Huntington's disease (HD), a genetic neurological disorder characterized by prominent motor and cognitive abnormalities, is key to understanding the mechanisms underlying the HD behavioral phenotype. We recorded extracellular spike activity in two symptomatic, freely behaving mouse models: R6/2 transgenics, which are based on a CBA x C57BL/6 background and show robust behavioral symptoms, and HD knock-in (KI) mice, which have a 129sv background and express relatively mild behavioral signs. We focused on prefrontal cortex and assessed firing patterns of individually recorded neurons as well as the amount of synchrony between simultaneously recorded neuronal pairs. At the single-unit level, spike trains in R6/2 transgenics were less variable and had a faster rate than their corresponding wild-type (WT) littermates but showed significantly less bursting. In contrast, KI and WT firing patterns were closely matched. An assessment of both WTs revealed that the R6/2 and KI difference could not be explained by a difference in WT electrophysiology. Thus, the altered pattern of individual spike trains in R6/2 mice appears to parallel their aggressive form of symptom expression. Both WT lines, however, showed a high proportion of synchrony between neuronal pairs (>85%) that was significantly attenuated in both corresponding HD models (decreases of approximately 20% and approximately 30% in R6/2s and knock-ins, respectively). The loss of spike synchrony, regardless of symptom severity, suggests a population-level deficit in cortical information processing that underlies HD progression.
authors.affiliation: Program in Neuroscience and Department of Psychological and Brain Sciences, Indiana University, Bloomington, Indiana 47405, USA.
authors.forename: Adam G
authors.initials: AG
authors.lastname: Walker
authors.forename: Benjamin R
authors.initials: BR
authors.lastname: Miller
authors.forename: Jenna N
authors.initials: JN
authors.lastname: Fritsch
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Barton
authors.forename: George V
authors.initials: GV
authors.lastname: Rebec