1. To test the mode of functional connectivity in the basal ganglia circuitry, we studied the activity of simultaneously recorded neurons in the globus pallidus (GP) of a behaving rhesus monkey. The cross-correlograms of pairs of neurons in the GP were compared with those of neurons in the thalamus and frontal cortex and to the cross-correlograms of pallidal pairs after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. In contrast with cortical and thalamic neuronal activity, almost all pairs (n = 76/81 pairs; 93.8%, 1,629/1,651 histograms; 98.7%) of GP neurons in the normal monkey were not driven by a common input. 3. The monkey was systemically treated with MPTP until the appearance of parkinsonian signs and an intermittent 7- to 11-Hz action/postural tremor. After the MPTP treatment, many pallidal neurons (49/140; 35%) became oscillatory, and 19% (n = 31/162) of pallidal pairs had oscillatory cross-correlograms. 4. These results support the model of parallel processing in the basal ganglia of normal monkeys and suggest a breakdown of the independent activity in the parkinsonian state.
1. Previous studies indicate that tonically active neurons (TANs) are the cholinergic interneurons of the striatum and predict that their activity is synchronized. To test whether TANs do fire synchronously, and whether dopamine depletion affects their synchronization, we recorded the simultaneous activity of several TANs in the putamens of two vervet monkeys before and after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment. 2. Cross-correlation analysis revealed that most pairs of TANS (33 of 54; 61.1%) fire synchronously at +/- 60-ms delay. Correlated activity was more common between neurons with characteristic response to reward (17 of 19 pairs; 89.5%). 3. Cross-correlation study of 24 triplets of TANS showed synchronization of spiking activity of all 3 TANS in only 29.2% of cases (7 of 24 triplets). Correlated activity of two of three possible pairs was found in 25% of the cases. 4. After MPTP treatment and the development of parkinsonian symptoms, most TANS' auto- and cross-correlograms (22 of 28 units; 78.6%; and 23 of 28 pairs; 82.1%) became oscillatory. The number of correlated pairs was slightly increased (24 of 28; 85.7%). The strength of the synchronization was not significantly different from the normal values. 5. These findings support the notion that TANs function as distributed, partially overlapping synchronized networks. However, a normal dopaminergic system is not essential for synchronization of TANs; on the contrary, dopaminergic activity may even have a desynchronizing effect on the basal ganglia's system.
Summary: Rhesus and vervet monkeys respond differently to treatment with I -methyl-4-phenyl-I ,2,3,6-tetrahydropyridine hydrochloride neurotoxin (MPTP). Both species develop akinesia. rigidity, and severe postural instability. However, rhesus monkeys only develop infrequent. short episodes of highfrequency tremor. whereas vervet monkeys have many prolonged episodes of low-frequency tremor. After MPTP treatment. the spiking activity of many pallidal neurons became oscillatory and highly correlated. Oscillatory autocorrelation functions were dominated by lower frequencies, crosscorrelograms by higher frequencies. The phase shift distribution of the oscillatory cross-correlograms of pallidal cells in MPTP-treated vcrvet monkey were clustered around 0 phase shift. unlike the oscillatory correlograms in the MPTP-treated rhesus monkey, which were widely distributed between 0" and Low-frequency resting tremor is frequently reported as the initial symptom of idiopathic Parkinson's disease (PD). Most patients (70-100%) manifest rest tremor during the course of the disease.' The typical frequency is 4-5 Hz; however, in several patients with early-onset parkinsonism, higher frequencies have been observed.' Posturalhction tremor of smaller amplitude and higher (6-12 Hz) frequency may be seen in most parkinsonian patients.3,4Understanding of the basic mechanisms of PD was enhanced by the discovery of I -methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride neurotoxin (MPTP). ',6 In people, MPTP can produce all major parkinsonian symptoms, including typical parkinsonian rest tremor.'.' The experimental study of tremor in parkinsonism was further advanced by the introduction of the MPTP- treated primate as a reliable animal model for PD."-" However, most primates develop akinesiahradykinesia, flexed posture, and rigidity but usually fail to develop low-frequency Short episodes of highfrequency (10-16 Hz) tremor have been described in MPTP-treated rhesus monkeys, possibly corresponding to postural/action tremor of human parkinsonian patients. In contrast, vervet (African green) monkeys develop prolonged episodes of low-frequency (4-6 Hz) tremor. 13. '4 This article summarizes the authors' electrophysiologic studies on the globus pallidus of MPTP-treated rhesus and vervet monkeys. These studies indicate that transient synchronization of neural activity is the hallmark of the spiking activity of neurons in the pallidum of MPTP-treated monkeys. If the tremor phenomenon is caused by these neural events, transient episodes of tremor coherency between different muscle groups or body segments should be observed. Testing for such episodes of synchronization of tremor was performed between different extremities of MPTP-treated monkeys and human parkinsonian patients.
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