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Figure 1. Schematic diagram of basal ganglia circuitry. Basal ganglia target structures are shown in gray. D1: DA D1 receptor subtype; D2: DA D2 receptor subtype; DA: Dopamine; ENK: Enkephalin; Glu: Glutamate; GPe: Globus pallidus external segment; GPi: Globus pallidus internal segment; SC: Superior colliculus; SNc: Substantia nigra pars compacta; SNr: Substantia nigra pars reticulata; SP: Substance P; STN: Subthalamic nucleus. Reprinted with permission from [8]
© 2007 Elsevier.
(Figure omitted. See article PDF.)
Figure 2. Events leading to the dopaminergic degeneration in Parkinson's disease. DA: Dopamine; SN: Substantia nigra.
(Figure omitted. See article PDF.)
Figure 3. Anatomical and electrophysiological characteristics of a substantia nigra pars compacta dopaminergic neuron. (A) Reconstruction of an electrophysiologically identified nigrostriatal dopaminergic neuron intracellularly labeled with horseradish peroxidase following in vivo intracellular recording. The inset at the lower right-hand corner shows the position of the neuron with respect to the boundaries of substantia nigra. (B & C) Identification of substantia nigra pars compacta neurons in extracellular (B) and whole-cell patch-clamp (C) recordings. (B) Example of extracellular recording from a dopaminergic neuron. (i) Spontaneous firing (ii) Interval histogram demonstrating regularity of spontaneous firing (iii) Shape of individual action potentials (average of 16 consecutive potentials). Note inflection on the rising phase of the action potential (arrow) (iv) Inhibition of firing after bath application of dopamine (30 µM). (C) Example of whole-cell patch-clamp recording. (i) Dopaminergic neuron. Top: Inward current induced by hyperpolarizing voltage commands (voltage-clamp), bottom: and voltage responses to step current pulses recorded in current clamp. Note depolarizing sag of the membrane potential (arrow) evoked by hyperpolarizing current pulses.
(ii) Nondopaminergic neuron. Above: currents induced by voltage steps (voltage-clamp), and responses to step current pulses (current-clamp). CC: Cerebella peduncle; DA: Doapamine; ML: Medila leminiscus; PC: Pars compacta; PR: Pars reticulata. (A) Reprinted from [40] © 1987 with permission from Elsevier (B & C) Reprinted from [42] © 2005 with permission from Elsevier.
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Figure 4. Simplified schematic of the vicious cycle that led to the final demise of nigral dopamine cells. Activated microglia (subsequent to immune activation or neuronal lesion caused by exposure to toxins such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine or 6-hydroxydopamine) can contribute to the degeneration of DA neurons by releasing neurotoxic factors. Cytokines can then activate...