Subthalamic nucleus high-frequency stimulation restores altered electrophysiological properties of cortical neurons in parkinsonian rat

PLoS One. 2013 Dec 31;8(12):e83608. doi: 10.1371/journal.pone.0083608. eCollection 2013.

Abstract

Electrophysiological recordings performed in parkinsonian patients and animal models have confirmed the occurrence of alterations in firing rate and pattern of basal ganglia neurons, but the outcome of these changes in thalamo-cortical networks remains unclear. Using rats rendered parkinsonian, we investigated, at a cellular level in vivo, the electrophysiological changes induced in the pyramidal cells of the motor cortex by the dopaminergic transmission interruption and further characterized the impact of high-frequency electrical stimulation of the subthalamic nucleus, a procedure alleviating parkinsonian symptoms. We provided evidence that a lesion restricted to the substantia nigra pars compacta resulted in a marked increase in the mean firing rate and bursting pattern of pyramidal neurons of the motor cortex. These alterations were underlain by changes of the electrical membranes properties of pyramidal cells including depolarized resting membrane potential and increased input resistance. The modifications induced by the dopaminergic loss were more pronounced in cortico-striatal than in cortico-subthalamic neurons. Furthermore, subthalamic nucleus high-frequency stimulation applied at parameters alleviating parkinsonian signs regularized the firing pattern of pyramidal cells and restored their electrical membrane properties.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dopamine / deficiency
  • Dopamine / physiology
  • Electric Stimulation Therapy*
  • Electrophysiological Phenomena
  • Motor Cortex / physiopathology
  • Nerve Block
  • Parkinsonian Disorders / physiopathology*
  • Parkinsonian Disorders / therapy*
  • Pyramidal Cells / physiopathology
  • Rats
  • Rats, Sprague-Dawley
  • Substantia Nigra / injuries
  • Substantia Nigra / physiopathology
  • Subthalamic Nucleus / physiopathology*

Substances

  • Dopamine

Grants and funding

This work was supported by Agence Nationale de la Recherche (grants number: ANR-05-JCJC-0076 and ANR-05-NEUR-013). B.D. was the recipient of a poste d’accueil from the Institut National de la Santé et de la Recherche Médicale (INSERM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.