Date of Completion

Spring 5-1-2015

Thesis Advisor(s)

John Salamone

Honors Major

Physiology and Neurobiology

Disciplines

Behavioral Neurobiology | Behavior and Behavior Mechanisms | Biological Psychology | Other Neuroscience and Neurobiology

Abstract

Parkinson’s Disease (PD) is a motor disorder with symptoms including resting tremor, akinesia, bradykinesia, and rigidity. A major neuropathological feature of PD is degeneration of nigrostriatal dopamine (DA) neurons. The resulting DA depletions lead to the production of severe motor deficits. Pharmacological agents that reduce DA transmission can also induce these motor abnormalities. In addition to the involvement of DA, drugs acting on acetylcholine, namely cholinomimetics, can induce or exacerbate Parkinsonian symptoms. In humans, one of the main motor symptoms associated with PD is resting tremor, occurring at a frequency of 3-7 Hz. This can be modeled in rodents using a tremulous jaw movement (TJM) model; these movements are defined as rapid, repetitive, vertical deflections of the lower jaw that are not directed at any particular stimulus. In rodents, TJMs are induced using the same pharmacological agents that induce Parkinsonism in humans, including neurotoxic or pharmacological depletion of striatal dopamine, dopamine depleting agents, such as tetrabenazine (TBZ), dopamine antagonists, and cholinomimetics, such as pilocarpine. Moreover, TJMs in rodents can be attenuated by antiparkinsonian agents, including L-DOPA, dopamine 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. In past studies, local field potentials (LFPs) have been recorded from PD patients undergoing implantation of stimulating electrodes in the subthalamic nucleus (STN). It has been shown that there is a high degree of coherence between STN LFPs and tremor as measured by EMG in PD patients. This study was done to determine if tremor-related local field potential (LFP) activity could be recorded from motor cortex or subthalamic nucleus 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 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 subthalamic nucleus. Tremor activity was not associated with increased activity 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, which may ultimately lead to identification of the oscillatory neural mechanisms involved in the generation of tremulous activity, as well as novel treatments for tremor disorders.

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