--- _id: '2623' abstract: - lang: eng text: Patients with Hodgkin's disease can develop paraneoplastic cerebellar ataxia because of the generation of autoantibodies against mGluR1 (mGluR1-Abs). Yet, the pathophysiological mechanisms underlying their motor coordination deficits remain to be elucidated. Here, we show that application of IgG purified from the patients' serum to cerebellar slices of mice acutely reduces the basal activity of Purkinje cells, whereas application to the flocculus of mice in vivo evokes acute disturbances in the performance of their compensatory eye movements. In addition, the mGluR1-Abs block induction of long-term depression in cultured mouse Purkinje cells, whereas the cerebellar motor learning behavior of the patients is affected in that they show impaired adaptation of their saccadic eye movements. Finally, postmortem analysis of the cerebellum of a paraneoplastic cerebellar ataxia patient showed that the number of Purkinje cells was significantly reduced by approximately two thirds compared with three controls. We conclude that autoantibodies against mGluR1 can cause cerebellar motor coordination deficits caused by a combination of rapid effects on both acute and plastic responses of Purkinje cells and chronic degenerative effects. author: - first_name: Michiel full_name: Coesmans, Michiel P last_name: Coesmans - first_name: Peter full_name: Sillevis-Smitt, Peter A last_name: Sillevis Smitt - first_name: David full_name: Linden, David J last_name: Linden - first_name: Ryuichi full_name: Ryuichi Shigemoto id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Tomoo full_name: Hirano, Tomoo last_name: Hirano - first_name: Yoshinori full_name: Yamakawa, Yoshinori last_name: Yamakawa - first_name: Adriaan full_name: Van Alphen, Adriaan M last_name: Van Alphen - first_name: Chongde full_name: Luo, Chongde last_name: Luo - first_name: Jos full_name: Van Der Geest, Jos N last_name: Van Der Geest - first_name: Johan full_name: Kros, Johan M last_name: Kros - first_name: Carlo full_name: Gaillard, Carlo A last_name: Gaillard - first_name: Maarten full_name: Frens, Maarten A last_name: Frens - first_name: Chris full_name: De Zeeuw, Chris I last_name: De Zeeuw citation: ama: Coesmans M, Sillevis Smitt P, Linden D, et al. Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Annals of Neurology. 2003;53(3):325-336. doi:10.1002/ana.10451 apa: Coesmans, M., Sillevis Smitt, P., Linden, D., Shigemoto, R., Hirano, T., Yamakawa, Y., … De Zeeuw, C. (2003). Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Annals of Neurology. Wiley-Blackwell. https://doi.org/10.1002/ana.10451 chicago: Coesmans, Michiel, Peter Sillevis Smitt, David Linden, Ryuichi Shigemoto, Tomoo Hirano, Yoshinori Yamakawa, Adriaan Van Alphen, et al. “Mechanisms Underlying Cerebellar Motor Deficits Due to MGluR1-Autoantibodies.” Annals of Neurology. Wiley-Blackwell, 2003. https://doi.org/10.1002/ana.10451. ieee: M. Coesmans et al., “Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies,” Annals of Neurology, vol. 53, no. 3. Wiley-Blackwell, pp. 325–336, 2003. ista: Coesmans M, Sillevis Smitt P, Linden D, Shigemoto R, Hirano T, Yamakawa Y, Van Alphen A, Luo C, Van Der Geest J, Kros J, Gaillard C, Frens M, De Zeeuw C. 2003. Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies. Annals of Neurology. 53(3), 325–336. mla: Coesmans, Michiel, et al. “Mechanisms Underlying Cerebellar Motor Deficits Due to MGluR1-Autoantibodies.” Annals of Neurology, vol. 53, no. 3, Wiley-Blackwell, 2003, pp. 325–36, doi:10.1002/ana.10451. short: M. Coesmans, P. Sillevis Smitt, D. Linden, R. Shigemoto, T. Hirano, Y. Yamakawa, A. Van Alphen, C. Luo, J. Van Der Geest, J. Kros, C. Gaillard, M. Frens, C. De Zeeuw, Annals of Neurology 53 (2003) 325–336. date_created: 2018-12-11T11:58:44Z date_published: 2003-03-01T00:00:00Z date_updated: 2021-01-12T06:58:39Z day: '01' doi: 10.1002/ana.10451 extern: 1 intvolume: ' 53' issue: '3' month: '03' page: 325 - 336 publication: Annals of Neurology publication_status: published publisher: Wiley-Blackwell publist_id: '4274' quality_controlled: 0 status: public title: Mechanisms underlying cerebellar motor deficits due to mGluR1-autoantibodies type: journal_article volume: 53 year: '2003' ... --- _id: '2625' abstract: - lang: eng text: Metabotropic glutamate receptor 1 (mGluR1) plays a crucial role in synaptic plasticity and motor learning in the cerebellum. We have studied activity-dependent changes in mGluR1 function in mouse cultured Purkinje neurons. Depolarizing stimulation potentiated Ca2+ and current responses to an mGluR1 agonist for several hours in the cultured Purkinje neurons. It also blocked internalization of mGluR1 and increased the number of mGluR1s on the cell membrane. We found that depolarization simultaneously increased transcription of Homer1a in Purkinje neurons. Homer1a inhibited internalization and increased cell-surface expression of mGluR1 when coexpressed in human embryonic kidney (HEK)-293 cells. Depolarization-induced Homer1a expression in Purkinje neurons was blocked by a mitogen-activated protein kinase (MAPK) inhibitor. Changes in internalization and mGluR1-mediated Ca2+ response were also blocked by inhibition of MAPK activity, suggesting that localization and activity of mGluR1 were regulated in the same signalling pathway as Homer1a expression. It is thus suggested that depolarization of the Purkinje neuron leads to the increment in mGluR1 responsiveness through MAPK activity and induction of Homer1a expression, which increases active mGluR1 on the cell surface by blocking internalization of mGluR1. author: - first_name: Itsunari full_name: Minami, Itsunari last_name: Minami - first_name: Mineko full_name: Kengaku, Mineko last_name: Kengaku - first_name: Sillevis full_name: Smitt, Sillevis P last_name: Smitt - first_name: Ryuichi full_name: Ryuichi Shigemoto id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Tomoo full_name: Hirano, Tomoo last_name: Hirano citation: ama: Minami I, Kengaku M, Smitt S, Shigemoto R, Hirano T. Long-term potentiation of mGluR1 activity by depolarization-induced Homer1a in mouse cerebellar Purkinje neurons. European Journal of Neuroscience. 2003;17(5):1023-1032. doi:10.1046/j.1460-9568.2003.02499.x apa: Minami, I., Kengaku, M., Smitt, S., Shigemoto, R., & Hirano, T. (2003). Long-term potentiation of mGluR1 activity by depolarization-induced Homer1a in mouse cerebellar Purkinje neurons. European Journal of Neuroscience. Wiley-Blackwell. https://doi.org/10.1046/j.1460-9568.2003.02499.x chicago: Minami, Itsunari, Mineko Kengaku, Sillevis Smitt, Ryuichi Shigemoto, and Tomoo Hirano. “Long-Term Potentiation of MGluR1 Activity by Depolarization-Induced Homer1a in Mouse Cerebellar Purkinje Neurons.” European Journal of Neuroscience. Wiley-Blackwell, 2003. https://doi.org/10.1046/j.1460-9568.2003.02499.x. ieee: I. Minami, M. Kengaku, S. Smitt, R. Shigemoto, and T. Hirano, “Long-term potentiation of mGluR1 activity by depolarization-induced Homer1a in mouse cerebellar Purkinje neurons,” European Journal of Neuroscience, vol. 17, no. 5. Wiley-Blackwell, pp. 1023–1032, 2003. ista: Minami I, Kengaku M, Smitt S, Shigemoto R, Hirano T. 2003. Long-term potentiation of mGluR1 activity by depolarization-induced Homer1a in mouse cerebellar Purkinje neurons. European Journal of Neuroscience. 17(5), 1023–1032. mla: Minami, Itsunari, et al. “Long-Term Potentiation of MGluR1 Activity by Depolarization-Induced Homer1a in Mouse Cerebellar Purkinje Neurons.” European Journal of Neuroscience, vol. 17, no. 5, Wiley-Blackwell, 2003, pp. 1023–32, doi:10.1046/j.1460-9568.2003.02499.x. short: I. Minami, M. Kengaku, S. Smitt, R. Shigemoto, T. Hirano, European Journal of Neuroscience 17 (2003) 1023–1032. date_created: 2018-12-11T11:58:44Z date_published: 2003-03-01T00:00:00Z date_updated: 2021-01-12T06:58:39Z day: '01' doi: 10.1046/j.1460-9568.2003.02499.x extern: 1 intvolume: ' 17' issue: '5' month: '03' page: 1023 - 1032 publication: European Journal of Neuroscience publication_status: published publisher: Wiley-Blackwell publist_id: '4273' quality_controlled: 0 status: public title: Long-term potentiation of mGluR1 activity by depolarization-induced Homer1a in mouse cerebellar Purkinje neurons type: journal_article volume: 17 year: '2003' ... --- _id: '2626' abstract: - lang: eng text: The expression pattern of metabotropic glutamate receptor Iα (mGluR1α) was immunohistochemically investigated in substantia nigra dopaminergic neurons of the macaque monkey. In normal monkeys, mGluR1α immunoreactivity was weakly observed in the dorsal tier of the substantia nigra pars compacta (SNc-d) where calbindin-D28k-containing dopaminergic neurons invulnerable to parkinsonian degeneration are specifically located. On the other hand, mGluR1α was strongly expressed in the ventral tier of the substantia nigra pars cornpacta (SNc-v). In monkeys treated with the parkinsonism-inducing drug, I-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), mGluR1α expression was decreased in dopaminergic neurons in the SNc-v that were spared its toxic action. These results suggest that mGluR1α expression may be involved at least partly in the vulnerability of dopaminergic neurons to parkinsonian insults. author: - first_name: Katsuyuki full_name: Kaneda, Katsuyuki last_name: Kaneda - first_name: Michiko full_name: Imanishi, Michiko last_name: Imanishi - first_name: Atsushi full_name: Nambu, Atsushi last_name: Nambu - first_name: Ryuichi full_name: Ryuichi Shigemoto id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Masahiko full_name: Takada, Masahiko last_name: Takada citation: ama: Kaneda K, Imanishi M, Nambu A, Shigemoto R, Takada M. Differential expression patterns of mGluR1α in monkey nigral dopamine neurons. Neuroreport. 2003;14(7):947-950. doi:10.1097/01.wnr.0000074344.81633.e4 apa: Kaneda, K., Imanishi, M., Nambu, A., Shigemoto, R., & Takada, M. (2003). Differential expression patterns of mGluR1α in monkey nigral dopamine neurons. Neuroreport. Lippincott, Williams & Wilkins. https://doi.org/10.1097/01.wnr.0000074344.81633.e4 chicago: Kaneda, Katsuyuki, Michiko Imanishi, Atsushi Nambu, Ryuichi Shigemoto, and Masahiko Takada. “Differential Expression Patterns of MGluR1α in Monkey Nigral Dopamine Neurons.” Neuroreport. Lippincott, Williams & Wilkins, 2003. https://doi.org/10.1097/01.wnr.0000074344.81633.e4. ieee: K. Kaneda, M. Imanishi, A. Nambu, R. Shigemoto, and M. Takada, “Differential expression patterns of mGluR1α in monkey nigral dopamine neurons,” Neuroreport, vol. 14, no. 7. Lippincott, Williams & Wilkins, pp. 947–950, 2003. ista: Kaneda K, Imanishi M, Nambu A, Shigemoto R, Takada M. 2003. Differential expression patterns of mGluR1α in monkey nigral dopamine neurons. Neuroreport. 14(7), 947–950. mla: Kaneda, Katsuyuki, et al. “Differential Expression Patterns of MGluR1α in Monkey Nigral Dopamine Neurons.” Neuroreport, vol. 14, no. 7, Lippincott, Williams & Wilkins, 2003, pp. 947–50, doi:10.1097/01.wnr.0000074344.81633.e4. short: K. Kaneda, M. Imanishi, A. Nambu, R. Shigemoto, M. Takada, Neuroreport 14 (2003) 947–950. date_created: 2018-12-11T11:58:45Z date_published: 2003-05-01T00:00:00Z date_updated: 2021-01-12T06:58:40Z day: '01' doi: 10.1097/01.wnr.0000074344.81633.e4 extern: 1 intvolume: ' 14' issue: '7' month: '05' page: 947 - 950 publication: Neuroreport publication_status: published publisher: Lippincott, Williams & Wilkins publist_id: '4272' quality_controlled: 0 status: public title: Differential expression patterns of mGluR1α in monkey nigral dopamine neurons type: journal_article volume: 14 year: '2003' ... --- _id: '2627' abstract: - lang: eng text: Despite its implications for higher order functions of the brain, little is currently known about the molecular basis of left-right asymmetry of the brain. Here we report that synaptic distribution of N-methyl-D-aspartate (NMDA) receptor GluRε2 (NR2B) subunits in the adult mouse hippocampus is asymmetrical between the left and right and between the apical and basal dendrites of single neurons. These asymmetrical allocations of ε2 subunits differentiate the properties of NMDA receptors and synaptic plasticity between the left and right hippocampus. These results provide a molecular basis for the structural and functional asymmetry of the mature brain. author: - first_name: Ryosuke full_name: Kawakami, Ryosuke last_name: Kawakami - first_name: Yoshiaki full_name: Shinohara, Yoshiaki last_name: Shinohara - first_name: Yuichiro full_name: Kato, Yuichiro last_name: Kato - first_name: Hiroyuki full_name: Sugiyama, Hiroyuki last_name: Sugiyama - first_name: Ryuichi full_name: Ryuichi Shigemoto id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 - first_name: Isao full_name: Ito, Isao last_name: Ito citation: ama: Kawakami R, Shinohara Y, Kato Y, Sugiyama H, Shigemoto R, Ito I. Asymmetrical allocation of NMDA receptor ε2 subunits in hippocampal circuitry. Science. 2003;300(5621):990-994. doi:10.1126/science.1082609 apa: Kawakami, R., Shinohara, Y., Kato, Y., Sugiyama, H., Shigemoto, R., & Ito, I. (2003). Asymmetrical allocation of NMDA receptor ε2 subunits in hippocampal circuitry. Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.1082609 chicago: Kawakami, Ryosuke, Yoshiaki Shinohara, Yuichiro Kato, Hiroyuki Sugiyama, Ryuichi Shigemoto, and Isao Ito. “Asymmetrical Allocation of NMDA Receptor Ε2 Subunits in Hippocampal Circuitry.” Science. American Association for the Advancement of Science, 2003. https://doi.org/10.1126/science.1082609. ieee: R. Kawakami, Y. Shinohara, Y. Kato, H. Sugiyama, R. Shigemoto, and I. Ito, “Asymmetrical allocation of NMDA receptor ε2 subunits in hippocampal circuitry,” Science, vol. 300, no. 5621. American Association for the Advancement of Science, pp. 990–994, 2003. ista: Kawakami R, Shinohara Y, Kato Y, Sugiyama H, Shigemoto R, Ito I. 2003. Asymmetrical allocation of NMDA receptor ε2 subunits in hippocampal circuitry. Science. 300(5621), 990–994. mla: Kawakami, Ryosuke, et al. “Asymmetrical Allocation of NMDA Receptor Ε2 Subunits in Hippocampal Circuitry.” Science, vol. 300, no. 5621, American Association for the Advancement of Science, 2003, pp. 990–94, doi:10.1126/science.1082609. short: R. Kawakami, Y. Shinohara, Y. Kato, H. Sugiyama, R. Shigemoto, I. Ito, Science 300 (2003) 990–994. date_created: 2018-12-11T11:58:45Z date_published: 2003-05-09T00:00:00Z date_updated: 2021-01-12T06:58:40Z day: '09' doi: 10.1126/science.1082609 extern: 1 intvolume: ' 300' issue: '5621' month: '05' page: 990 - 994 publication: Science publication_status: published publisher: American Association for the Advancement of Science publist_id: '4271' quality_controlled: 0 status: public title: Asymmetrical allocation of NMDA receptor ε2 subunits in hippocampal circuitry type: journal_article volume: 300 year: '2003' ... --- _id: '2629' abstract: - lang: eng text: The release of neurotransmitters is modulated by presynaptic metabotropic glutamate receptors (mGluRs), which show a highly selective expression and subcellular location in glutamatergic terminals in the hippocampus. Using immunocytochemistry, we investigated whether one of the receptors, mGluR7, whose level of expression is governed by the postsynaptic target, was present in GABAergic terminals and whether such terminals targeted particular cells. A total of 165 interneuron dendritic profiles receiving 466 synapses (82% mGluR7a-positive) were analysed. The presynaptic active zones of most GAD-(77%) or GABA-positive (94%) synaptic boutons on interneurons innervated by mGluR7a-enriched glutamatergic terminals (mGluR7a-decorated) were immunopositive for mGluR7a. GABAergic terminals on pyramidal cells and most other interneurons in str. oriens were mGluR7a-immunonegative. The mGluR7a-decorated cells were mostly somatostatin- and mGluR1α-immunopositive neurons in str. oriens and the alveus. Their GABAergic input mainly originated from VIP-positive terminals, 90% of which expressed high levels of mGluR7a in the presynaptic active zone. Parvalbumin-positive synaptic terminals were rare on mGluR7a-decorated cells, but on these neurons 73% of them were mGluR7a-immunopositive. Some type II synapses innervating interneurons were immunopositive for mGluR7b, as were some type I synapses. Because not all target cells of VIP-positive neurons are known it has not been possible to determine whether mGluR7 is expressed in a target-cell-specific manner in the terminals of single GABAergic cells. The activation of mGluR7 may decrease GABA release to mGluR7-decorated cells at times of high pyramidal cell activity, which elevates extracellular glutamate levels. Alternatively, the presynaptic receptor may be activated by as yet unidentified endogenous ligands released by the GABAergic terminals or the postsynaptic dendrites. author: - first_name: Péter full_name: Somogyi, Péter last_name: Somogyi - first_name: Yannis full_name: Dalezios, Yannis last_name: Dalezios - first_name: Rafael full_name: Luján, Rafael last_name: Luján - first_name: John full_name: Roberts, John D last_name: Roberts - first_name: Masahiko full_name: Watanabe, Masahiko last_name: Watanabe - first_name: Ryuichi full_name: Ryuichi Shigemoto id: 499F3ABC-F248-11E8-B48F-1D18A9856A87 last_name: Shigemoto orcid: 0000-0001-8761-9444 citation: ama: Somogyi P, Dalezios Y, Luján R, Roberts J, Watanabe M, Shigemoto R. High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus. European Journal of Neuroscience. 2003;17(12):2503-2520. doi:10.1046/j.1460-9568.2003.02697.x apa: Somogyi, P., Dalezios, Y., Luján, R., Roberts, J., Watanabe, M., & Shigemoto, R. (2003). High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus. European Journal of Neuroscience. Wiley-Blackwell. https://doi.org/10.1046/j.1460-9568.2003.02697.x chicago: Somogyi, Péter, Yannis Dalezios, Rafael Luján, John Roberts, Masahiko Watanabe, and Ryuichi Shigemoto. “High Level of MGluR7 in the Presynaptic Active Zones of Select Populations of GABAergic Terminals Innervating Interneurons in the Rat Hippocampus.” European Journal of Neuroscience. Wiley-Blackwell, 2003. https://doi.org/10.1046/j.1460-9568.2003.02697.x. ieee: P. Somogyi, Y. Dalezios, R. Luján, J. Roberts, M. Watanabe, and R. Shigemoto, “High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus,” European Journal of Neuroscience, vol. 17, no. 12. Wiley-Blackwell, pp. 2503–2520, 2003. ista: Somogyi P, Dalezios Y, Luján R, Roberts J, Watanabe M, Shigemoto R. 2003. High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus. European Journal of Neuroscience. 17(12), 2503–2520. mla: Somogyi, Péter, et al. “High Level of MGluR7 in the Presynaptic Active Zones of Select Populations of GABAergic Terminals Innervating Interneurons in the Rat Hippocampus.” European Journal of Neuroscience, vol. 17, no. 12, Wiley-Blackwell, 2003, pp. 2503–20, doi:10.1046/j.1460-9568.2003.02697.x. short: P. Somogyi, Y. Dalezios, R. Luján, J. Roberts, M. Watanabe, R. Shigemoto, European Journal of Neuroscience 17 (2003) 2503–2520. date_created: 2018-12-11T11:58:46Z date_published: 2003-06-01T00:00:00Z date_updated: 2021-01-12T06:58:41Z day: '01' doi: 10.1046/j.1460-9568.2003.02697.x extern: 1 intvolume: ' 17' issue: '12' month: '06' page: 2503 - 2520 publication: European Journal of Neuroscience publication_status: published publisher: Wiley-Blackwell publist_id: '4269' quality_controlled: 0 status: public title: High level of mGluR7 in the presynaptic active zones of select populations of GABAergic terminals innervating interneurons in the rat hippocampus type: journal_article volume: 17 year: '2003' ...