Reduced GABA content in the motor thalamus during effective deep brain stimulation of the subthalamic nucleus

Alessandro Stefani, Ernesto Fedele, Mariangela Pierantozzi, Salvatore Galati, Francesco Marzetti, Antonella Peppe, Francesco Saverio Pastore, Giorgio Bernardi, Paolo Stanzione

Research output: Contribution to journalArticlepeer-review

Abstract

Deep brain stimulation (DBS) of the subthalamic nucleus (STN), in Parkinson's disease (PD) patients, is a well established therapeutic option, but its mechanisms of action are only partially known. In our previous study, the clinical transitions from OFF- to ON-state were not correlated with significant changes of GABA content inside GPi or substantia nigra reticulata. Here, biochemical effects of STN-DBS have been assessed in putamen (PUT), internal pallidus (GPi), and inside the antero-ventral thalamus (VA), the key station receiving pallidothalamic fibers. In 10 advanced PD patients undergoing surgery, microdialysis samples were collected before and during STN-DBS. cGMP, an index of glutamatergic transmission, was measured in GPi and PUT by radioimmunoassay, whereas GABA from VA was measured by HPLC. During clinically effective STN-DBS, we found a significant decrease in GABA extracellular concentrations in VA (-30%). Simultaneously, cGMP extracellular concentrations were enhanced in PUT (+200%) and GPi (+481%). These findings support a thalamic dis-inhibition, in turn re-establishing a more physiological corticostriatal transmission, as the source of motor improvement. They indirectly confirm the relevance of patterning (instead of mere changes of excitability) and suggest that a rigid interpretation of the standard model, at least when it indicates the hyperactive indirect pathway as key feature of hypokinetic signs, is unlikely to be correct. Finally, given the demonstration of a key role of VA in inducing clinical relief, locally administration of drugs modulating GABA transmission in thalamic nuclei could become an innovative therapeutic strategy.

Original languageEnglish
Article number17
JournalFrontiers in Systems Neuroscience
Issue numberAPRIL 2011
DOIs
Publication statusPublished - Apr 5 2011

Keywords

  • Antero-ventral thalamus
  • cGMP
  • GABA
  • Globus pallidus
  • Glutamate
  • Stereotactic neurosurgery
  • Subthalamus
  • UPDRS

ASJC Scopus subject areas

  • Neuroscience (miscellaneous)
  • Cellular and Molecular Neuroscience
  • Cognitive Neuroscience
  • Developmental Neuroscience

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