Neurophysiology of the brain stem in Parkinson's disease

Abstract

Parkinson's disease (PD) is predominantly idiopathic in origin, and a large body of evidence indicates that gastrointestinal (GI) dysfunctions are a significant comorbid clinical feature; these dysfunctions include dysphagia, nausea, delayed gastric emptying, and severe constipation, all of which occur commonly before the onset of the well-known motor symptoms of PD. Based on a distinct distribution pattern of Lewy bodies (LB) in the enteric nervous system (ENS) and in the preganglionic neurons of the dorsal motor nucleus of the vagus (DMV), and together with the early onset of GI symptoms, it was suggested that idiopathic PD begins in the ENS and spreads to the central nervous system (CNS), reaching the DMV and the substantia nigra pars compacta (SNpc). These two areas are connected by a recently discovered monosynaptic nigro-vagal pathway, which is dysfunctional in rodent models of PD. An alternative hypothesis downplays the role of LB transport through the vagus nerve and proposes that PD pathology is governed by regional or cell-restricted factors as the leading cause of nigral neuronal degeneration. The purpose of this brief review is to summarize the neuronal electrophysiological findings in the SNpc and DMV in PD.

Keywords: brain stem; neurodegenerative disorders; vagus; whole cell patch clamp.

Fig. 1.

Summary of the Parkinson’s disease (PD)-induced alterations in the basal ganglia and nigro-vagal pathways. Graphic representation of the pathophysiological basal ganglia and nigro-vagal neurocircuitry in PD. Regardless of the etiology, in PD there are increased glutamate inputs from the subthalamic (STN) and pedunculopontine nuclei (PPn) to the substantia nigra pars compacta (SNpc), and from STN to the internal segment of the globus pallidus (GPi) and the substantia nigra pars reticulata (SNr). Striatal alterations are determined by the decreased/lack of dopamine (DA) modulation, which results in increased inhibition of the external segment of the globus pallidus (GPe) and disinhibition of the GPi/SNr, resulting in increased inhibition of the thalamus. Similarly, the loss of dopaminergic inputs from the SNpc might impact the functions of the dorsal motor nucleus of the vagus (DMV) significantly, inducing vagally mediated gastrointestinal dysfunctions associated with PD. The glutamate excitotoxicity observed commonly in PD may also occur within nucleus tractus solitarius (NTS) to DMV synapse, providing an additional level of dysregulation of vagal control of gastrointestinal function. Thicker arrows represent increased neurotransmission. Conversely, dotted lines indicate decreased neurotransmission. The black arrow between NTS and DMV indicates a mixed excitatory and inhibitory neurotransmission.