Oscillatory Cortical Activity in an Animal Model of Dystonia Caused by Cerebellar Dysfunction.

Daniela Popa,Ioana Antoaneta Georgescu,Adrian Ştefan Pană,Alexandru Răzvan Şteopoaie,Elena Laura Georgescu,Vlad Petru Morozan,Carmen Denise Mihaela Zahiu,Ana-Maria Zăgrean

doi:10.3389/fncel.2018.00390

Abstract

The synchronization of neuronal activity in the sensorimotor cortices is crucial for motor control and learning. This synchrony can be modulated by upstream activity in the cerebello-cortical network. However, many questions remain over the details of how the cerebral cortex and the cerebellum communicate. Therefore, our aim is to study the contribution of the cerebellum to oscillatory brain activity, in particular in the case of dystonia, a severely disabling motor disease associated with altered sensorimotor coupling. We used a kainic-induced dystonia model to evaluate cerebral cortical oscillatory activity and connectivity during dystonic episodes. We performed microinjections of low doses of kainic acid into the cerebellar vermis in mice and examined activities in somatosensory, motor and parietal cortices. We showed that repeated applications of kainic acid into the cerebellar vermis, for five consecutive days, generate reproducible dystonic motor behavior. No epileptiform activity was recorded on electrocorticogram (ECoG) during the dystonic postures or movements. We investigated the ECoG power spectral density and coherence between motor cortex, somatosensory and parietal cortices before and during dystonic attacks. During the baseline condition, we found a phenomenon of permanent adaptation with a change of baseline locomotor activity coupled to an ECoG gamma band increase in all cortices. In addition, after kainate administration, we observed an increase in muscular activity, but less signs of dystonia together with modulations of the ECoG power spectra with an increase in gamma band in motor, parietal and somatosensory cortices. Moreover, we found reduced coherence in all measured frequency bands between the motor cortex and somatosensory or parietal cortices compared to baseline. In conclusion, examination of cortical oscillatory activities in this animal model of chronic dystonia caused by cerebellar dysfunction reveals a disruption in the coordination of neuronal activity across the cortical sensorimotor/parietal network, which may underlie motor skill deficits.

Highlights

There is increasing evidence that oscillations in the sensorimotor cortices can be modulated by the cerebellum via cerebellothalamo-cortical pathways
The present study examined the contribution of the cerebellum to motor, somatosensory and parietal oscillatory activities by using a mouse model of dystonia
The first signs of dystonia appeared after ∼2–3 min following the injection with a general slowing down of movements or the hind limb being held near the trunk while the mouse was exploring

Summary

Introduction

There is increasing evidence that oscillations in the sensorimotor cortices can be modulated by the cerebellum via cerebellothalamo-cortical pathways. The role of the cerebellum in modulating cerebral oscillations and associated coherence between brain regions involved in motor execution remains poorly understood. Dystonia is a motor disorder in which a cerebellar dysfunction has been recently recognized, despite the absence of cardinal cerebellar signs (ataxia, dysmetria). Abnormal oscillatory activities in the motor cortex and abnormal learning are recognized as dystonic typical traits. This has led to propose that a distorted cerebellar output in the cerebellothalamo-cortical pathway may pathologically influence the motor cortex (Prudente et al, 2014). Abnormalities restricted to cerebellum were sufficient to cause dystonia and the cerebellar dysfunction was coupled to dystonic movements (LeDoux, 2011; Raike et al, 2013; Fremont et al, 2014; White and Sillitoe, 2017)

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