Localization and Physiological Roles of Metabotropic Glutamate Receptors in the Indirect Pathway

Abstract

Parkinson’s disease (PD) is a common neurodegenerative disorder characterized by disabling motor impairments including tremor, rigidity, and bradykinesia. The primary pathological change giving rise to the symptoms of Parkinson’s disease is loss of dopaminergic neurons in the substantia nigra pars compacta that modulate the function of neurons in the striatum and other nuclei in the basal ganglia (BG) motor circuit (Figure. 1). Currently, the most effective pharmacological agents for treatment of PD include levodopa (L-DOPA), the immediate precursor of dopamine, and other drugs that replace the lost dopaminergic modulation of BG function) Unfortunately, dopamine replacement therapy ultimately fails in most patients due to loss of efficacy with progression of the disease and severe motor and psychiatric side effects.2 Because of this, a great deal of effort has been focused on developing new approaches for treatment of PD.