首页|Hypothetical Mechanism of Resting Tremor in Parkinson's Disease
Hypothetical Mechanism of Resting Tremor in Parkinson's Disease
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NSTL
Springer Nature
A hypothetical mechanism of resting tremor onset in Parkinson's disease has been proposed. This mechanism is based on modifications of the efficiency of excitatory inputs to the striatal spiny cells caused by dopamine deficiency. These modifications lead to a reorganization of activity in neural network, including the neocortex, thalamus, basal ganglia, cerebellum, as well as the subthalamic and pedunculopontine nuclei. As a result of this modification, the activity of striatonigral cells decreases, and causes disinhibition of neurons in the internal part of the globus pallidus. At the same time, the activity of striatopallidal cells increases leading to a decrease in the activity of neurons in the external part of the globus pallidus, and a subsequent decrease in their inhibitory effect on neurons in the internal part of the globus pallidus, as well as in the subthalamic nucleus and neocortex. As a result, the activity of neurons in these structures increases. Strengthening the GABAergic input from the internal part of the globus pallidus to the neurons of the subthalamic nucleus that leads to hyperpolarization of the neuronal membrane, contributes to the generation of burst discharges with a tremor frequency. An increase in the activity of neurons in the subthalamic nucleus leads to an increase in the excitation of their target cells in the pedunculopontine nucleus and deep cerebellar nuclei. The subsequent enhancement of the excitatory effect of the cerebellum on thalamic neurons is transmitted to the neocortex and striatum. According to the proposed mechanism, the degree of excitation of neurons in the subthalamic nucleus determines the tremor amplitude and explains the fact that the increase in activity in the cerebellum, thalamus, and neocortex correlates with the severity of tremor. It follows from the proposed mechanism that since selective agonists of dopamine D2 receptors and/or antagonists of adenosine A2A receptors should promote the induction of LTD on striatopallidal cells, weakening their inhibitory effect on neurons in the external part of the globus pallidus, and the subsequent increase in the inhibition of the subthalamic nucleus, these substances can be used to suppress resting tremor. These consequences of our hypothesis have experimental confirmation.
NSTL
Springer Nature
