Altered cortical processing of sensory input in Huntington disease mouse models

Abstract

Huntington disease (HD), a hereditary neurodegenerative disorder, manifests as progressively impaired movement and cognition. Although early abnormalities of neuronal activity in striatum are well established in HD models, there are fewer in vivo studies of the cortex. Here, we record local field potentials (LFPs) in YAC128 HD model mice versus wild-type mice. In multiple cortical areas, limb sensory stimulation evokes a greater change in LFP power in YAC128 mice. Mesoscopic imaging using voltage-sensitive dyes reveal more extensive spread of evoked sensory signals across the cortical surface in YAC128 mice. YAC128 layer 2/3 sensory cortical neurons ex vivo show increased excitatory events, which could contribute to enhanced sensory responses in vivo. Cortical LFP responses to limb stimulation, visual and auditory input are also significantly increased in zQ175 HD mice. Results presented here extend knowledge of HD beyond ex vivo studies of individual neurons to the intact cortical network.

Longitudinal assessment of water-reaching reveals altered cortical activity and fine motor coordination defects in a Huntington Disease model

“…Consistent with other studies that report global activation of the cortex and involvement of the ipsilateral hemisphere during limb movement (Heming et al, 2019; Soma et al, 2019; Brunner et al, 2020; Quarta et al, 2022), our results also revealed widespread cortical activation across both hemispheres during water-reaching. Although we did not see wide-spread enhanced cortical activity in HD mice as some work indicates (Arnoux et al, 2018; Burgold et al, 2019; Sepers et al, 2021) compared to WT (except in M2), global cortical activation associated with reaching increased over time in HD mice (but not WT). The lack of increased cortical activity may be due to differences in task-performing awake versus anesthetized animals, HD mouse models and/or cortical areas examined.…”

“…The copyright holder for this preprint this version posted September 5, 2022. ; https://doi.org/10.1101/2022.09.02.505959 doi: bioRxiv preprint indicators of neuronal activity. Using mesoscale voltage-sensitive dye imaging, our group has shown that hindlimb stimulation evokes a larger area and longer lasting cortical response in anesthetized HD compared to WT mice (Sepers et al, 2021). Given recent neurophysiology studies have demonstrated the involvement of multiple brain regions in sensation, cognition and movement (Pinto et al, 2019;Steinmetz et al, 2019), widefield functional assessment of neuronal circuit changes during task performance is needed throughout the time course of HD disease pathology.…”