Primary Motor Cortex of the Parkinsonian Monkey: Differential Effects on the Spontaneous Activity of Pyramidal Tract-Type Neurons

Abstract

Dysfunction of primary motor cortex (M1) is thought to contribute to the pathophysiology of parkinsonism. What specific aspects of M1 function are abnormal remains uncertain, however. Moreover, few models consider the possibility that distinct cortical neuron subtypes may be affected differently. Those questions were addressed by studying the resting activity of intratelencephalic-type corticostriatal neurons (CSNs) and distant-projecting lamina 5b pyramidal-tract type neurons (PTNs) in the macaque M1 before and after the induction of parkinsonism by administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Contrary to previous reports, the general population of M1 neurons (i.e., PTNs, CSNs, and unidentified neurons) showed reduced baseline firing rates following MPTP, attributable largely to a marked decrease in PTN firing rates. CSN firing rates were unmodified. Although burstiness and firing patterns remained constant in M1 neurons as a whole and CSNs in particular, PTNs became more bursty post-MPTP and less likely to fire in a regular-spiking pattern. Rhythmic spiking (found in PTNs predominantly) occurred at beta frequencies (14-32 Hz) more frequently following MPTP. These results indicate that MPTP intoxication induced distinct modifications in the activity of different M1 neuronal subtypes. The particular susceptibility of PTNs suggests that PTN dysfunction may be an important contributor to the pathophysiology of parkinsonian motor signs.

Therapeutic mechanisms of high-frequency stimulation in Parkinson’s disease and neural restoration via loop-based reinforcement

“…We measured the fraction of power allocated in the 8-30-Hz band for each PYN and we found that this fraction increased in 331 out of 600 PYNs when under PD conditions, which is consistent with the increment of oscillations in that band reported by ref. 76. The average increment in the 8-30 Hz power across these 331 PYNs was 5.9 ± 6.0% (mean ± SD, range: 0-53.9%) and resulted in no prominent oscillation in that band, which is consistent with the analysis of single unit recordings of MPTP-treated NHPs reported in ref.…”

“…In cortex, the percentage of PYNs with random, regular, or bursty patterns mildly changed at the transition from normal to PD conditions (random: 270 vs. 290; regular: 97 vs. 121; bursty: 231 vs. 184; normal vs. PD; definition of the patterns is given in ref. 76 and SI Note 4), and nonsignificant changes (Wilcoxon rank-sum test, P > 0:05) were reported for the distribution of the firing rates across the PYNs (Fig. 4 A, B, D, and E), the population-average firing rate (Fig.…”

“…4F), consistently with ref. 76 (M1 group). We measured the fraction of power allocated in the 8-30-Hz band for each PYN and we found that this fraction increased in 331 out of 600 PYNs when under PD conditions, which is consistent with the increment of oscillations in that band reported by ref.…”

Deep Brain Stimulation for Movement Disorders of Basal Ganglia Origin: Restoring Function or Functionality?

“…Among these, abnormal bursting and oscillatory fluctuations of neuronal discharge are particularly noticeable [147][148][149][150][151][152]. Oscillatory activity can be identified in electrophysiological recordings of the activity of single neurons in GPi, SNr, STN, and MC in animals and patients with PD [153]. The proportion of cells in STN and GPi that discharge in bursts is also greatly increased in parkinsonism [143,144,152,154,155].…”

“…In contrast, interventions directed at the PPN have revealed significant motoric effects in animal experiments [55]. Thus, PPN inactivation in normal primates reduces body movements of arms, trunk, and legs [142][143][144][145][146], and PPN injection of a GABA-A receptor antagonist, or low-frequency stimulation of PPN, alleviates experimental akinesia in monkeys, presumably by increasing PPN activity [146][147][148][149][150][151][152][153][154][155][156]. This constellation of findings suggests the possibility that the descending basal ganglia projections to the brainstem may play a greater role in the pathophysiology of akinesia/bradykinesia and movement than is commonly assumed.…”