Abstract
The degeneration of dopaminergic neurons in the substantia nigra pars compacta leads to parkinsonian motor symptoms via changes in electrophysiological activity throughout the basal ganglia. High-frequency deep brain stimulation (DBS) partially treats these symptoms, but the mechanisms are unclear. We hypothesize that motor symptoms of Parkinson’s disease (PD) are associated with increased information transmission from basal ganglia output neurons to motor thalamus input neurons and that therapeutic DBS of the subthalamic nucleus (STN) treats these symptoms by reducing this extraneous information transmission. We tested these hypotheses in a unilateral, 6-hydroxydopamine-lesioned rodent model of hemiparkinsonism. Information transfer between basal ganglia output neurons and motor thalamus input neurons increased in both the orthodromic and antidromic directions with hemiparkinsonian (hPD) onset, and these changes were reversed by behaviorally therapeutic STN-DBS. Omnidirectional information increases in the parkinsonian state underscore the detrimental nature of that pathological information and suggest a loss of information channel independence. Therapeutic STN-DBS reduced that pathological information, suggesting an effective increase in the number of independent information channels. We interpret these data with a model in which pathological information and fewer information channels diminishes the scope of possible motor activities, driving parkinsonian symptoms. In this model, STN-DBS restores information-channel independence by eliminating or masking the parkinsonism-associated information, and thus enlarges the scope of possible motor activities, alleviating parkinsonian symptoms.
Highlights
Deep brain stimulation (DBS) is an accepted therapy for several neurological conditions (Benabid et al, 1998; Hariz et al, 2013)
To test this hypothesis experimentally, we used a rodent model of Parkinson’s disease (PD) to examine neuronal information directed from basal ganglia efferents in substantia nigra pars reticulata (SNr), to the ventral anterior (VA) thalamus under healthy and hemiparkinsonian conditions, and in the presence of behaviorally therapeutic STNDBS
The hallmark motor symptoms of PD are driven by changes in basal ganglia neural activity
Summary
Deep brain stimulation (DBS) is an accepted therapy for several neurological conditions (Benabid et al, 1998; Hariz et al, 2013). DBS of the subthalamic nucleus (STN) or globus pallidus internus (GPi) can alleviate motor symptoms of Parkinson’s disease (PD), including bradykinesia, rigidity, and tremor (Limousin-Dowsey et al, 1999; Lyons and Pahwa, 2004) These motor symptoms are associated with pathological neural activity in basal ganglia that propagates into the thalamocortical motor loop (Chesselet and Delfs, 1996; Galvan et al, 2015). If disordered firing patterns contribute to parkinsonian symptoms, we hypothesize that they do so by transmitting pathological information from basal ganglia to downstream structures in the thalamocortical motor loop (Grill et al, 2004) To test this hypothesis experimentally, we used a rodent model of PD to examine neuronal information directed from basal ganglia efferents in substantia nigra pars reticulata (SNr), to the ventral anterior (VA) thalamus under healthy and hemiparkinsonian (hPD) conditions, and in the presence of behaviorally therapeutic STNDBS. These hPD-associated informational increases were reversed entirely by therapeutic STN-DBS
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