Alterations in neuronal activity in basal ganglia-thalamocortical circuits in the parkinsonian state

Abstract

In patients with Parkinson's disease and in animal models of this disorder, neurons in the basal ganglia and related regions in thalamus and cortex show changes that can be recorded by using electrophysiologic single-cell recording techniques, including altered firing rates and patterns, pathologic oscillatory activity and increased inter-neuronal synchronization. In addition, changes in synaptic potentials or in the joint spiking activities of populations of neurons can be monitored as alterations in local field potentials (LFPs), electroencephalograms (EEGs) or electrocorticograms (ECoGs). Most of the mentioned electrophysiologic changes are probably related to the degeneration of diencephalic dopaminergic neurons, leading to dopamine loss in the striatum and other basal ganglia nuclei, although degeneration of non-dopaminergic cell groups may also have a role. The altered electrical activity of the basal ganglia and associated nuclei may contribute to some of the motor signs of the disease. We here review the current knowledge of the electrophysiologic changes at the single cell level, the level of local populations of neural elements, and the level of the entire basal ganglia-thalamocortical network in parkinsonism, and discuss the possible use of this information to optimize treatment approaches to Parkinson's disease, such as deep brain stimulation (DBS) therapy.

Keywords: LFP; Parkinson’s disease; animal models; basal ganglia; electrophysiology; extracellular recording; parkinsonism.

Figure 1

Firing rate changes in the basal ganglia-thalamo-cortical motor circuit in parkinsonism. The yellow box indicates the interconnected basal ganglia nuclei that receive extrinsic input from the cortical and thalamic regions. For simplicity some connections have been omitted from this diagram. The left panel indicates the circuits in the “Normal” state, and the right shows the overall changes in activity that have been associated with parkinsonism. Blue and red arrows indicate inhibitory and excitatory connections, respectively. The thickness of the arrows corresponds to their presumed activity. Abbreviations: CM, centromedian nucleus of thalamus; D1 and D2, dopamine receptor subtypes; GPe, external segment of the globus pallidus; GPi, internal segment of the globus pallidus; LH, lateral habenula; PF, parafascicular nucleus of the thalamus; PPN, pedunculopontine nucleus; SC, superior colliculus; SNc, substantia nigra pars compacta; SNr, substantia nigra pars reticulata; STN, subthalamic nucleus; VA, ventral anterior nucleus of thalamus; VL, ventrolateral nucleus of thalamus.

Figure 2

Segregated basal ganglia—thalamocortical and basal ganglia—thalamostriatal functional loops. Information related to each functional modality is processed through segregated regions of the cerebral cortex, the basal ganglia and thalamic nuclei. Abbreviations: See Figure 1 and MD, mediodorsal nucleus; PFdl, dorsolateral extension of the PF; VAmc, part magnocellular of VA; VApc, part parvocellular of VA; VLc, caudal part of VL; VLd, dorsal VL; VLo, pars oralis of VL; VLm, medial part of VL (based on Alexander et al., , ; Middleton and Strick, 2000).

Figure 3

Examples of extracellular recordings of individual neurons in the GPe, GPi and STN of monkeys in normal conditions and after MPTP treatment. Arrows indicate examples of bursts in an STN neuron. Horizontal line represents 1 s.

Figure 4

Relationship between oscillatory activity changes in the cortico-basal ganglia network and progression of parkinsonism, in an MPTP-treated monkey. The animal was chronically instrumented for recording of EcoG signals from the primary motor cortex (M1). In addition, local field potential signals were recorded from STN and GPi through macroelectrodes that were repeatedly inserted into the same basal ganglia locations throughout the course of the experiment. (A) Temporal progression of the development of parkinsonism induced by MPTP injections, based on weekly evaluations. The solid black line shows the stage of parkinsonism. The cumulative dose of MPTP is shown as a gray line with open circles, where each circle corresponds to a single MPTP injection. Stages 1–3 represent mild, moderate, and moderately-severe parkinsonism, as judged by a parkinsonian rating scale. (B) Relative spectral power (mean ± SEM) of M1, STN and GPi signals (EEG, LFPs) across the different stages. (C) Coherence between M1 and STN, STN and GPi, and M1 and GPi signals in the 7.8–15.5 Hz frequency range across different stages of parkinsonism during periods of wakefulness. *p < 0.05 vs. baseline (2-way ANOVA with post hoc Holm-Sidak test). Modified from Devergnas et al. (2014), with permission.