---
_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'
...