Abstract
Tremulous jaw movements (TJMs) are rapid vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus. In rodents, TJMs are induced by neurochemical conditions that parallel those seen in human Parkinsonism, including neurotoxic or pharmacological depletion of striatal dopamine (DA), DA antagonism, and cholinomimetic administration. Moreover, TJMs in rodents can be attenuated by antiparkinsonian agents, including levodopa (L-DOPA), DA agonists, muscarinic antagonists, and adenosine A2A antagonists. In human Parkinsonian patients, exaggerated physiological synchrony is seen in the beta frequency band in various parts of the cortical/basal ganglia/thalamic circuitry, and activity in the tremor frequency range (3–7 Hz) also has been recorded. The present studies were undertaken to determine if tremor-related local field potential (LFP) activity could be recorded from motor cortex (M1) or subthalamic nucleus (STN) during the TJMs induced by the muscarinic agonist pilocarpine, which is a well-known tremorogenic agent. Pilocarpine induced a robust TJM response that was marked by rhythmic electromyographic (EMG) activity in the temporalis muscle. Compared to periods with no tremor activity, TJM epochs were characterized by increased LFP activity in the tremor frequency range in both neocortex and STN. Tremor activity was not associated with increased synchrony in the beta frequency band. These studies identified tremor-related LFP activity in parts of the cortical/basal ganglia circuitry that are involved in the pathophysiology of Parkinsonism. This research may ultimately lead to identification of the oscillatory neural mechanisms involved in the generation of tremulous activity, and promote development of novel treatments for tremor disorders.
Highlights
Parkinsonism is a broad family of disorders that includes idiopathic Parkinson’s disease (PD), which results from degeneration of nigrostriatal dopamine (DA) neurons (Hornykiewicz, 1973), and drug-induced Parkinsonism, which is induced by drugs that interfere with DA transmission (e.g., DA antagonists, DA depleting agents; Marsden et al, 1975; McEvoy, 1983), and cholinomimetics such as anticholinesterases and muscarinic agonists (Ott and Lannon, 1992; Aarsland et al, 2003)
A total of 38 local field potential (LFP) electrodes (n = 19 M1 electrodes; n = 19 subthalamic nucleus (STN) electrodes) and five EMG electrodes across five animals were used in the current analysis
Pilocarpine is a well known tremorogenic agent, and previous studies have shown that pilocarpine-induced tremulous jaw movement (TJM) are reduced by antiparkinsonian drugs (Salamone et al, 2005; Betz et al, 2009; Collins et al, 2010; Podurgiel et al, 2013a), conditional neural knockout of adenosine A2A receptors (Salamone et al, 2013), and deep brain stimulation of the STN (CollinsPraino et al, 2013)
Summary
Parkinsonism is a broad family of disorders that includes idiopathic Parkinson’s disease (PD), which results from degeneration of nigrostriatal dopamine (DA) neurons (Hornykiewicz, 1973), and drug-induced Parkinsonism, which is induced by drugs that interfere with DA transmission (e.g., DA antagonists, DA depleting agents; Marsden et al, 1975; McEvoy, 1983), and cholinomimetics such as anticholinesterases and muscarinic agonists (Ott and Lannon, 1992; Aarsland et al, 2003).Tremor-Related Brain Field PotentialsThe cardinal motor symptoms of Parkinsonism include akinesia, bradykinesia, rigidity, and a resting tremor that typically occurs in the 3–7 Hz frequency range (Marsden et al, 1975). Motor dysfunctions resembling drug-induced Parkinsonism are produced in rodents by the same pharmacological agents that induce human Parkinsonism, and resting tremor can be modeled in rodents using the tremulous jaw movement (TJM) model. TJMs, which are defined as ‘‘rapid, repetitive vertical deflections of the lower jaw that resemble chewing but are not directed at any particular stimulus’’ (Salamone et al, 1998), have a local frequency of 3–7 Hz, which parallels that of Parkinsonian resting tremor (Cousins et al, 1998; Salamone et al, 1998, 2015a; Collins et al, 2010; Podurgiel et al, 2013b). Considerable evidence indicates that TJMs in rodents are a valid model for the exploration of the pharmacology, neurochemistry and physiology of drug-induced tremor (Salamone et al, 1998, 2008b, 2013, 2015a; Collins-Praino et al, 2011; Podurgiel et al, 2013a,b, 2015; Herrera-Meza et al, 2014; Gandía et al, 2015)
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