Discharge Rate of Substantia Nigra Pars Reticulata Neurons Is Reduced In Non-Parkinsonian Monkeys With Apomorphine-Induced Orofacial Dyskinesia

Abstract

Involuntary movements (dyskinesia) are a common symptom of dopamine-replacement therapy in parkinsonian patients, neuroleptic drug treatment of mental patients, and tic disorders. Levodopa-induced dyskinesia has been shown to be associated with substantial reduction of firing rate in the internal part of the globus pallidus. This study characterizes the changes that occur in the activity of the substantia nigra pars reticulata (SNr) of non-parkinsonian (normal) monkeys with apomorphine (APO)-induced orofacial dyskinesia. We conducted extracellular recordings of SNr neurons of two monkeys before and after induction of orofacial dyskinesia by systemic administration of APO. Involuntary orofacial movements appeared a few minutes after the injections and lasted 20-40 min. Almost all recorded neurons changed their firing rate after APO injection (96%), and most declined (70%). The mean amplitude of decreases was also larger than that of increases (40 vs. 21% of the control rate). Changes in firing pattern were not significant on average. Pairs of SNr neurons were uncorrelated before APO injection, similar to the normal pallidum. However, unlike the increased correlations in the pallidum that accompany parkinsonism, orofacilal dyskinesia in non-parkinsonian monkeys was not associated with changes in correlation between SNr neurons. We conclude that normal monkeys treated with APO can model orofacial dyskinesia and tic disorders that are a consequence of dopaminergic over-activity. These symptoms appear to be more related to reduced firing rate of SNr neurons and thus to disinhibition of their targets, than to changes in pattern and synchronization.

Constitutively Active TRPC3 Channels Regulate Basal Ganglia Output Neurons

“…The inhibitory output from SNr GABA projection neurons (and probably also GPi GABA projection neurons) is encoded in their firing frequency and pattern (Hikosaka and Wurtz, 1983;Nevet et al, 2004;Hikosaka, 2007). Therefore, the spiking properties (frequency and pattern) of SNr GABA projection neurons are critical to movement control.…”

“…Parkinsonian movement disorders are often associated with abnormalities in SNr GABA neuron firing. Recordings in animal models of Parkinson's disease and Parkinson's disease patients indicate that the SNr GABA neuron output in parkinsonian brain is often altered in its intensity and/or pattern (Bergman et al, 1998;Obeso et al, 2000;Hutchison et al, 2004;Nevet et al, 2004). Further demonstrating the importance of SNr in motor control and Parkinson's disease, inactivation of SNr in a primate model of Parkinson's disease has been shown to ameliorate parkinsonian motor symptoms (Wichmann et al, 2001).…”

“…The activity of basal ganglia output neurons [SNr GABA neurons and the GABA neurons of the internal segment of globus pallidus (GPi)] plays critical roles in movement control. Parkinsonian movement disorders are often associated with alterations in the firing rate and/or firing patterns of these basal ganglia output neurons (Nevet et al, 2004;Tang et al, 2005;Rivlin-Etzion et al, 2006;Wichmann and Soares, 2006;.…”

GABAergic output of the basal ganglia

“…The enhanced GABAergic output would excessively suppress the target areas including the SC, MLR, PPN, thalamo-cortical circuits, and possibly mouth movement and vocalization centers, leading to akinesia or hypokinesia. On the other hand, dyskinesias induced by l-DOPA (dopamine precursor) or apomorphine (dopamine agonist) are associated with a reduction of the basal ganglia GABAergic outputs (Nevet et al, 2004). The depressed GABAergic output would be insufficient to suppress the motor centers mentioned above, which leads to excessive body movements, dyskinesia.…”

A noninvasive, fast and inexpensive tool for the detection of eye open/closed state in primates

“…This is usually done offline, after videotaping the animal's behavior (e.g., Nevet et al, 2004). However this method is very cumbersome and time consuming, and therefore is not feasible for processing large amounts of data.…”