Dysfunctional Behavioral Modulation of Corticostriatal Communication in the R6/2 Mouse Model of Huntington’s Disease

S Lee Hong,Lauren J Walker,George V Rebec,Scott J Barton,Desirée Cossyleon,Wajeeha A Hussain,David R Borchelt

doi:10.1371/journal.pone.0047026

S Lee Hong, Lauren J Walker + Show 5 more

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https://doi.org/10.1371/journal.pone.0047026

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Journal: PloS one	Publication Date: Oct 4, 2012
Citations: 76	License type: CC BY 4.0

Affiliation: Indiana University Bloomington

Abstract

BackgroundIn Huntington’s disease (HD), motor symptoms develop prior to the widespread loss of neurons in striatum and cerebral cortex. The aim of this study was to examine dysfunctional patterns of corticostriatal communication during spontaneously occurring behaviors in a transgenic mouse model of HD.Methodology/Principal FindingsLocal field potentials (LFPs) were recorded from two closely interconnected areas, motor cortex and dorsal striatum, in wild-type controls (WT, n = 14) and a widely used transgenic HD model (R6/2 mice, n = 12). All mice were between the ages of 7–9 weeks, a critical period of motor symptom development in R6/2s. Recordings were obtained while the mice were behaving freely in an open field. Specific LFP activity was extracted using timestamps for three increasingly demanding motor behaviors: 1) resting; 2) grooming; and 3) active exploration. Power spectral densities (PSD) were obtained for the cortical and striatal LFPs as well as coherence levels and relative phase across the frequency spectrum. In both brain regions, only R6/2s showed high frequency LFP oscillations during rest and grooming. As behavior increased from resting to exploring, corticostriatal synchrony at high frequencies declined in R6/2s, completely opposite to the WT pattern. R6/2s also exhibited nearly in-phase corticostriatal activity (cortex phase leads of ∼5°), while the WTs consistently showed cortical phase lags of ∼20° across all assessed behaviors, indicating a lead role for striatum.Conclusions/SignificanceOur results add to growing evidence for altered communication between cortex and striatum in HD and suggest more generally that increasingly demanding motor behaviors differentially modulate corticostriatal communication. Our data also suggest conduction delays in R6/2 corticostriatal transmission, leading to compensatory speeding of LFP activity, as evidenced by the presence of high frequency LFP oscillations.

Highlights

In Huntington’s disease (HD), a fatally inherited neurological condition, motor control deteriorates along with cortical and striatal neurons [1]
Relative to WT, cortical and striatal local field potentials (LFPs) in R6/2 mice possess a broader power spectral density (PSD) distribution at higher frequencies, consistent with higher signal unpredictability
Despite the onset of motor symptoms, R6/2 mice engaged in a similar number of episodes of all three behaviors. These mice, spent significantly more time grooming and exploring, and less time resting than the WT controls (Figure 2). Across each of these behaviors, markedly different corticostriatal LFP activity was evident in the high frequency activity and peaks that appeared consistently in the power spectra of R6/2 but not WT mice

Summary

Introduction

In Huntington’s disease (HD), a fatally inherited neurological condition, motor control deteriorates along with cortical and striatal neurons [1]. Long before these neurons die, they become dysfunctional [2,3], suggesting that altered information flow through corticostriatal circuitry sets the stage for HD and its subsequent progression. In support of this view, both cortical and striatal neurons show aberrant patterns of spike activity in behaving transgenic mice that model HD [4,5].

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