Altered neuronal activity in the pedunculopontine nucleus: An electrophysiological study in a rat model of Parkinson’s disease

Highlights

• The PPN neurons were hyperactive in 6-OHDA lesioned rats.

• The firing pattern of PPN neurons was changed due to the 6-OHDA lesion.

• The loss of dopamine in rats resulted in the changes of LFP activities.

Abstract

The pedunculopontine nucleus (PPN) is a new deep brain stimulation target for treating Parkinson’s disease (PD). But the alterations of the PPN electrophysiological activities in PD are still debated. To investigate these potential alterations, extracellular single unit and local field potential (LFP) activities in the PPN were recorded in unilateral hemispheric 6-hydroxydopamine (6-OHDA) lesioned rats and in control rats, respectively. The spike activity results revealed two types of neurons (Type I and Type II) with distinct electrophysiological characteristics in the PPN. Both types of neurons had increased firing rate and changed firing pattern in lesioned rats when compared to control rats. Specifically, Type II neurons showed an increased firing rate when the rat state was switched from rest to locomotion. The LFP results demonstrated that lesioned rats had lower LFP power at 0.7–12 Hz and higher power at 12–30 Hz than did control animals in either resting or locomotor state. These findings provide a better understanding of the effects of 6-OHDA lesion on neuronal activities in the PPN and also provide a proof of the link between this structure and locomotion, which contributes to better understanding the mechanisms of the PPN functioning in the pathophysiology of PD.

Introduction

Parkinson’s disease (PD) is mainly characterized by the loss of dopaminergic neurons in the pars compacta of the substantia nigra (SNc) and the successive changes in the activity of the basal ganglia [1]. The pedunculopontine nucleus (PPN) is the most inferior structure in the midbrain that has extensive connections to the basal ganglia, which can be best illustrated by the connections of the PPN with the basal ganglia output nuclei. That is, the PPN mainly receives dense inhibitory projections from the substantia nigra pars reticulata (SNr) and excitatory projections from the subthalamic nucleus (STN) [2], [3], [4].

The PPN is considered as part of the mesencephalic locomotor region, and thus is possible to elicit the initiation, maintenance and modulation of gait and postural stability[5]. In addition, the PPN has a function of direct control of muscles via connections to the spinal cord [6], [7]. Regarding this, the PPN has recently attracted a great deal of interest among researchers as a promising target for deep brain stimulation (DBS) to relieve symptoms of PD [8], [9], [10], [11], [12].

Previous studies [13], [14], [15], [16] have reported that the firing activities and the firing pattern of PPN neurons are altered in parkinsonian rats compared to normal ones. Nonetheless, the alterations of the PPN in PD are still debated since some of these studies reported the hyperactivity of PPN neurons but others reported the hypoactivity of PPN neurons. Moreover, most of these electrophysiological studies above mentioned are performed on animals under the anesthetized state, which has a confounding of uncertain effect and a limitation for reflecting the actual alterations. Under the awake and behaving state, how the activities of PPN neurons changes in a rat model of PD still remains unclear. Recently, the firing characteristics of PPN have been recorded in parkinsonian human but have a deficiency of the lack of comparison with control group [17]. Given the interest in the PPN as a therapeutic target, to study the alterations of neuronal discharges and local field potential (LFP) activities in the PPN is essential for exploring the mechanisms by which the PPN contributes to the pathophysiology of PD.

In this study, with the purpose of investigating whether the loss of dopamine can affect neuronal activities in the PPN, 16-channel multi-units as well as LFPs were recorded simultaneously in the PPN of unilateral dopaminergic cell in lesioned or control rats in either an inattentive resting state or locomotor state of walking along a ladder.