title: Subthalamic deep brain stimulation reduces pathological information transmission to the thalamus in a rat model of parkinsonism.
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.
authors.affiliation: Department of Bioengineering, University of Utah Salt Lake City, UT, USA.
authors.forename: Collin J
authors.initials: CJ
authors.lastname: Anderson
authors.affiliation: Department of Bioengineering, University of Utah Salt Lake City, UT, USA.
authors.forename: Daylan T
authors.initials: DT
authors.lastname: Sheppard
authors.affiliation: Department of Bioengineering, University of Utah Salt Lake City, UT, USA.
authors.forename: Rachel
authors.initials: R
authors.lastname: Huynh
authors.affiliation: Department of Bioengineering, University of Utah Salt Lake City, UT, USA.
authors.forename: Daria Nesterovich
authors.initials: DN
authors.lastname: Anderson
authors.affiliation: Department of Bioengineering, University of Utah Salt Lake City, UT, USA.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Polar
authors.affiliation: Department of Bioengineering, University of Utah Salt Lake City, UT, USA.
authors.forename: Alan D
authors.initials: AD
authors.lastname: Dorval
mesh_terms: D000200:Action Potentials / Q000502:physiology; D018663:Adrenergic Agents / Q000633:toxicity; D000818:Animals; D001703:Biophysics; D046690:Deep Brain Stimulation / Q000379:methods*; D004195:Disease Models, Animal; D005260:Female; D007839:Functional Laterality / Q000187:drug effects / Q000502:physiology; D008297:Male; D008474:Medial Forebrain Bundle / Q000502:physiology; D009415:Nerve Net / Q000502:physiology*; D016627:Oxidopamine / Q000633:toxicity; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000473:pathology* / Q000628:therapy*; D051381:Rats; D020318:Rats, Long-Evans; D020531:Subthalamic Nucleus / Q000502:physiology*; D013788:Thalamus / Q000473:pathology*
chemical_list: D018663:Adrenergic Agents; D016627:Oxidopamine
keywords: 6-hydroxydopamine; deep brain stimulation; neural information; parkinson disease; substantia nigra pars reticulata; thalamic nuclei