Biochemical and electrophysiological changes of substantia nigra pars reticulata driven by subthalamic stimulation in patients with Parkinson's disease.
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.
Galati
Salvatore
S
I.R.C.C.S. Fondazione S., Via Ardeatina 306-00133, Rome, Italy.
Mazzone
Paolo
P
Fedele
Ernesto
E
Pisani
Antonio
A
Peppe
Antonella
A
Pierantozzi
Mariangela
M
Brusa
Livia
L
Tropepi
Domenicantonio
D
Moschella
Vincenzo
V
Raiteri
Maurizio
M
Stanzione
Paolo
P
Bernardi
Giorgio
G
Stefani
Alessandro
A
D000200:Action Potentials / Q000528:radiation effects; D000368:Aged; D000704:Analysis of Variance; D001923:Brain Chemistry / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism; D046690:Deep Brain Stimulation / Q000379:methods*; D005260:Female; D005583:Fourier Analysis; D006801:Humans; D008297:Male; D017551:Microdialysis / Q000379:methods / Q000706:statistics & numerical data; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy; D013378:Substantia Nigra / Q000378:metabolism* / Q000503:physiopathology*; D020531:Subthalamic Nucleus / Q000528:radiation effects*; D013997:Time Factors
D006152:Cyclic GMP