title: Signals through the striatopallidal indirect pathway stop movements by phasic excitation in the substantia nigra.
abstract: The striatum and subthalamic nucleus (STN) are the input stations of the basal ganglia and receive excitatory afferents from the cerebral cortex. The basal ganglia control voluntary movements through three parallel pathways mediated by the input stations: the hyperdirect pathway, which conveys direct cortical inputs to the substantia nigra pars reticulata (SNr), the output nucleus, through the STN; the direct pathway, which arises from striatal neurons expressing dopamine D1 receptors and projects to the SNr; and the indirect pathway, which arises from striatal neurons expressing dopamine D2 receptors (D2Rs) and projects indirectly to the SNr by way of the globus pallidus (GP) and STN. Our previous study showed that immunotoxin-mediated cell targeted ablation of D2R-expressing striatal neurons in mice induced motor hyperactivity. To elucidate the mechanism underlying the hyperactivity, here we examined neuronal activity in the GP and SNr. The ablation of D2R-expressing striatal neurons had little effect on spontaneous activity in the GP and SNr, but induced dramatic changes in the cortically evoked triphasic response composed of early excitation, inhibition, and late excitation in the GP and SNr (i.e., reduced inhibition in the GP, and reduced late excitation in the GP and SNr). In contrast, the ablation of striatal cholinergic interneurons, which also express D2Rs, did not show such effects. Therefore, the reduction of the cortically evoked late excitation in the SNr seems to be responsible for hyperactivity. These observations suggest that phasic late excitation in the SNr through the striatopallidal indirect pathway plays a key role in stopping movements.
authors.affiliation: Division of System Neurophysiology, National Institute for Physiological Sciences, Okazaki 444-8585, Japan.
authors.forename: Hiromi
authors.initials: H
authors.lastname: Sano
authors.forename: Satomi
authors.initials: S
authors.lastname: Chiken
authors.forename: Takatoshi
authors.initials: T
authors.lastname: Hikida
authors.forename: Kazuto
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nambu
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000502:physiology*; D005260:Female; D005917:Globus Pallidus / Q000502:physiology*; D006801:Humans; D006948:Hyperkinesis / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009434:Neural Pathways / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013378:Substantia Nigra / Q000502:physiology*