TY - JOUR
T1 - Comparison of MPTP-induced changes in spontaneous neuronal discharge in the internal pallidal segment and in the substantia nigra pars reticulata in primates
AU - Wichmann, Thomas
AU - Bergman, Hagai
AU - Starr, Philip A.
AU - Subramanian, Thyagarajan
AU - Watts, Ray L.
AU - DeLong, Mahlon R.
N1 - Funding Information:
Acknowledgements We thank L.H. Rowland, M.A. Kliem and C. Oliver for expert technical assistance. This work was supported by a grant from the National Institute of Neurological Disorders and Stroke (5-R01-NS15417-14), by a grant from the University Research Council of Emory University (T.S.), and by grants from the American Parkinson’s Disease Association (T.S., P.S.).
PY - 1999
Y1 - 1999
N2 - The basal ganglia are currently viewed as components of segregated corticosubcortical reentrant circuits. One of these circuits, the 'motor' circuit, is critically involved in the development of parkinsonian motor signs. Current pathophysiologic models postulate that parkinsonism is associated with increased activity in the basal ganglia output nuclei. The neuronal activity in the motor portion of one of these output nuclei, the internal segment of the globus pallidus (GPi), has been characterized in detail in intact and parkinsonian animals, but the neuronal activity in the second major basal ganglia output nucleus, the substantia nigra pars reticulata (SNr), has received far less attention. This study in primates represents a comparison of the effects of parkinsonism, induced by injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetfahydropyridine (MPTP), on the neuronal discharge in the GPi and SNr. These electrophysiologic recording experiments were carried out in three African green and two rhesus monkeys. One hundred and twenty-four neurons were recorded in the GPi before treatment with MPTP, and 93 neurons thereafter. In the SNr, 55 cells were recorded before treatment with MPTP, and 41 cells thereafter. MPTP induced a non-significant increase in the average discharge rate and a significant decrease in the median interspike interval length (ISI) in the GPi (by 13%), whereas no changes were detected in either parameter in the SNr. The average ISI distributions were markedly asymmetric in both structures, and could be modeled by a logarithmic normal distribution. With the MPTP treatment, the mode of the ISI distribution fell by 24% in the GPi (P ≤ 0.01), whereas it did not change significantly in the SNr. An algorithm that detects burst discharges in the raw ISI data (based on the method by Legendy and Salcman) detected a significant increase in the proportion of action potentials that participated in bursts of discharge in both structures (increase by 257% in the GPi, and by 67% in the SNr). Power spectral and autocorrelation analysis revealed that treatment with MPTP increased the proportion of cells with oscillatory burst patterns at 3-8 Hz in both structures (from 0.8% to 27% of all neurons in the GPi, and from none to 10% in the SNr). The results show that neuronal discharge in the SNr is affected in parkinsonism, but that the changes in the SNr are less pronounced then those seen in the GPi.
AB - The basal ganglia are currently viewed as components of segregated corticosubcortical reentrant circuits. One of these circuits, the 'motor' circuit, is critically involved in the development of parkinsonian motor signs. Current pathophysiologic models postulate that parkinsonism is associated with increased activity in the basal ganglia output nuclei. The neuronal activity in the motor portion of one of these output nuclei, the internal segment of the globus pallidus (GPi), has been characterized in detail in intact and parkinsonian animals, but the neuronal activity in the second major basal ganglia output nucleus, the substantia nigra pars reticulata (SNr), has received far less attention. This study in primates represents a comparison of the effects of parkinsonism, induced by injections of the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetfahydropyridine (MPTP), on the neuronal discharge in the GPi and SNr. These electrophysiologic recording experiments were carried out in three African green and two rhesus monkeys. One hundred and twenty-four neurons were recorded in the GPi before treatment with MPTP, and 93 neurons thereafter. In the SNr, 55 cells were recorded before treatment with MPTP, and 41 cells thereafter. MPTP induced a non-significant increase in the average discharge rate and a significant decrease in the median interspike interval length (ISI) in the GPi (by 13%), whereas no changes were detected in either parameter in the SNr. The average ISI distributions were markedly asymmetric in both structures, and could be modeled by a logarithmic normal distribution. With the MPTP treatment, the mode of the ISI distribution fell by 24% in the GPi (P ≤ 0.01), whereas it did not change significantly in the SNr. An algorithm that detects burst discharges in the raw ISI data (based on the method by Legendy and Salcman) detected a significant increase in the proportion of action potentials that participated in bursts of discharge in both structures (increase by 257% in the GPi, and by 67% in the SNr). Power spectral and autocorrelation analysis revealed that treatment with MPTP increased the proportion of cells with oscillatory burst patterns at 3-8 Hz in both structures (from 0.8% to 27% of all neurons in the GPi, and from none to 10% in the SNr). The results show that neuronal discharge in the SNr is affected in parkinsonism, but that the changes in the SNr are less pronounced then those seen in the GPi.
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U2 - 10.1007/s002210050696
DO - 10.1007/s002210050696
M3 - Article
C2 - 10323285
AN - SCOPUS:0032896281
SN - 0014-4819
VL - 125
SP - 397
EP - 409
JO - Experimental Brain Research
JF - Experimental Brain Research
IS - 4
ER -