Roles of Motor Cortex Neuron Classes in Reach-Related Modulation for Hemiparkinsonian Rats.

Min Li,Qin He,Xiaojun Wang,Dadian Chen,Yue Sun,Min Wang,Xiaomeng Yao,Qingmei Jia,Yuchuan Li,Xuenan Wang,Xuenan Wang,Shuang Sun,Feiyu Chen,Zhiwei Zhu,Mengnan Guo,Xiao Zhang,Feng He

doi:10.3389/fnins.2021.645849

Abstract

Disruption of the function of the primary motor cortex (M1) is thought to play a critical role in motor dysfunction in Parkinson’s disease (PD). Detailed information regarding the specific aspects of M1 circuits that become abnormal is lacking. We recorded single units and local field potentials (LFPs) of M1 neurons in unilateral 6-hydroxydopamine (6-OHDA) lesion rats and control rats to assess the impact of dopamine (DA) cell loss during rest and a forelimb reaching task. Our results indicated that M1 neurons can be classified into two groups (putative pyramidal neurons and putative interneurons) and that 6-OHDA could modify the activity of different M1 subpopulations to a large extent. Reduced activation of putative pyramidal neurons during inattentive rest and reaching was observed. In addition, 6-OHDA intoxication was associated with an increase in certain LFP frequencies, especially those in the beta range (broadly defined here as any frequency between 12 and 35 Hz), which become pathologically exaggerated throughout cortico-basal ganglia circuits after dopamine depletion. Furthermore, assessment of different spike-LFP coupling parameters revealed that the putative pyramidal neurons were particularly prone to being phase-locked to ongoing cortical oscillations at 12–35 Hz during reaching. Conversely, putative interneurons were neither hypoactive nor synchronized to ongoing cortical oscillations. These data collectively demonstrate a neuron type-selective alteration in the M1 in hemiparkinsonian rats. These alterations hamper the ability of the M1 to contribute to motor conduction and are likely some of the main contributors to motor impairments in PD.

Highlights

Many studies have been conducted to understand the correlations between primary motor cortex (M1) neuron activity and voluntary movement in Parkinson’s disease (PD), since basal ganglia circuits are closely tied to the cortex (Reiner et al, 2010; Wu et al, 2011; Quiroga-Varela et al, 2013)
Using multichannel recording arrays implanted in layer 5 of the M1, we recorded extracellular single-neuron spiking activity and local field potentials (LFPs) in control and unilateral 6-hydroxydopamine (6-OHDA-treated) rats during rest and skilled reach-to-grasp movements. This forelimb reaching task has been shown to have limited usefulness in assessing the generation and execution of voluntary limb movements, such as in chronic animal models of Parkinson’s disease (Parr-Brownlie and Hyland, 2005; Pasquereau et al, 2016; Zanos et al, 2018; Holt et al, 2019). This task was used in our previous study, and we found that the rats were able to successfully perform the reach-to-grasp task with one forelimb and exhibited characteristics of 6-OHDAinduced modifications in spiking and LFPs in the thalamic parafascicular nucleus (Wang et al, 2016)
It is noteworthy that the alterations in the specific frequency of LFPs was accompanied by increases in the phase synchronization of M1 spikes to LFPs in the 12– 35 Hz range, which excessively emerge in cortico-basal ganglia circuits after dopamine depletion during reaching movement

Summary

Introduction

Many studies have been conducted to understand the correlations between primary motor cortex (M1) neuron activity and voluntary movement in Parkinson’s disease (PD), since basal ganglia circuits are closely tied to the cortex (Reiner et al, 2010; Wu et al, 2011; Quiroga-Varela et al, 2013). PD symptoms are accompanied by certain alterations, including abnormal firing rates and patterns, pathologic oscillatory activity, and increased synchronization throughout basal ganglia-cortical circuits (Walters et al, 2007; Ellens and Leventhal, 2013; Devergnas et al, 2014; Valencia et al, 2014; Galvan et al, 2015; Wang et al, 2015; Dupre et al, 2016). The available data are inconsistent regarding whether there is a decrease or an increase in the movement-related activity of M1 neurons (Parr-Brownlie and Hyland, 2005; Pasquereau and Turner, 2011; Pasquereau and Turner, 2013), and some studies have reported an increase (Lefaucheur, 2005) or no change in cortical neuron activity (Goldberg et al, 2002)

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