Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson's disease

Salvatore Galati, Paolo Mazzone, Ernesto Fedele, Antonio Pisani, Antonella Peppe, Mariangela Pierantozzi, Livia Brusa, Domenicantonio Tropepi, Vincenzo Moschella, Maurizio Raiteri, Paolo Stanzione, Giorgio Bernardi, Alessandro Stefani

Research output: Contribution to journalArticle

Abstract

To understand the events underlying the clinical efficacy of deep brain stimulation (DBS) of the subthalamic nucleus (STN), electrophysiological recordings and microdialysis evaluations were carried out in the substantia nigra pars reticulata (SNr), one of the two basal ganglia (BG) nuclei targeted by STN output, in patients with Parkinson's disease (PD). Clinically effective STN-DBS caused a significant increase of the SNr firing rate. The poststimulus histogram (PSTH) showed an excitation peak at 1.92-3.85 ms after the STN stimulus. The spontaneous discharge of SNr neurons was driven at the frequency of the stimulation (130 Hz), as shown in the autocorrelograms (AutoCrl). The fast Fourier transform (FFT) analysis showed a peak at 130 Hz, and a less pronounced second one at 260 Hz. Accordingly, in the distribution of the interspike intervals (ISIs), the mode was earlier, and skewness more asymmetric. Biochemically, the increased excitatory driving from the STN was reflected by a clear-cut increase in cyclic guanosine 3',5'-monophosphate (cGMP) levels in the SNr. These results indicate that the beneficial effect of DBS in PD patients is paralleled with a stimulus-synchronized activation of the STN target, SNr. Our findings suggest that, during STN-DBS, a critical change towards a high-frequency oscillatory discharge occurs.

Original languageEnglish
Pages (from-to)2923-2928
Number of pages6
JournalEuropean Journal of Neuroscience
Volume23
Issue number11
DOIs
Publication statusPublished - Jun 2006

Keywords

  • cGMP
  • Deep brain stimulation
  • Parkinson's disease
  • Substantia nigra
  • Subthalamic nucleus

ASJC Scopus subject areas

  • Neuroscience(all)

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    Galati, S., Mazzone, P., Fedele, E., Pisani, A., Peppe, A., Pierantozzi, M., Brusa, L., Tropepi, D., Moschella, V., Raiteri, M., Stanzione, P., Bernardi, G., & Stefani, A. (2006). Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson's disease. European Journal of Neuroscience, 23(11), 2923-2928. https://doi.org/10.1111/j.1460-9568.2006.04816.x