Physiology of MPTP Tremor

Abstract

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.

Dissociation of motor symptoms during deep brain stimulation of the subthalamic nucleus in the region of the internal capsule

“…Subsequently, the effect of stimulation at 80% of MT on motor behavior, including rigidity, akinesia and bradykinesia was evaluated intermittently over a period of two months. In contrast to the other motor signs, and consistent with previous experience in the macaque MPTP model (Bergman, et al, 1998, Burns, et al, 1983), tremor was minimal and inconsistent in this animal (See Table 1). As a result, those data were excluded from statistical analysis.…”

Regulation of Substantia Nigra Pars Reticulata GABAergic Neuron Activity by H2O2 via Flufenamic Acid-Sensitive Channels and KATP Channels

“…In human PD and in PD animal models, increased SNr output causes abnormal inhibition of thalamocortical neurons (Albin et al, 1989; DeLong, 1990; MacLeod et al, 1990; Wichmann and DeLong, 1996, 2006; Murer et al, 1997; Bergman et al, 1998; Hurtado et al, 1999; Hutchison et al, 2004). Linking these observations to the present findings, PD is associated with impaired activity of mitochondrial complex I and increased oxidative stress possibly including elevated H 2 O 2 production in the SN (Parker et al, 1989; Schapira et al, 1990; Greenamyre et al, 2001; Turnbull et al, 2001; Dauer and Przedborski, 2003; Dawson and Dawson, 2003; Lin and Beal, 2006).…”

Modulations in Oscillatory Frequency and Coupling in Globus Pallidus with Increasing Parkinsonian Severity

“…While all subjects developed a small amplitude postural tremor, the parkinsonian syndrome with rhesus macaques most resembled the akinetic-rigid subtype seen in human PD patients. Alternative animal models, such as the African green monkey, are known to develop prominent tremor and more resemble the tremor subtype of PD patients (Bergman et al, 1998). Therefore, the results of this study cannot directly inform the physiological differences underlying the tremor-dominant parkinsonian subtype.…”