---
_id: '2475'
abstract:
- lang: eng
text: 'Background: One of the best-characterized causative factors of Alzheimer''s
disease (AD) is the generation of amyloid-β peptide (Aβ). AD subjects are at high
risk of epileptic seizures accompanied by aberrant neuronal excitability, which
in itself enhances Aβ generation. However, the molecular linkage between epileptic
seizures and Aβ generation in AD remains unclear. Results: X11 and X11-like (X11L)
gene knockout mice suffered from epileptic seizures, along with a malfunction
of hyperpolarization-activated cyclic nucleotide gated (HCN) channels. Genetic
ablation of HCN1 in mice and HCN1 channel blockage in cultured Neuro2a (N2a) cells
enhanced Aβ generation. Interestingly, HCN1 levels dramatically decreased in the
temporal lobe of cynomolgus monkeys (Macaca fascicularis) during aging and were
significantly diminished in the temporal lobe of sporadic AD patients. Conclusion:
Because HCN1 associates with amyloid-β precursor protein (APP) and X11/X11L in
the brain, genetic deficiency of X11/X11L may induce aberrant HCN1 distribution
along with epilepsy. Moreover, the reduction in HCN1 levels in aged primates may
contribute to augmented Aβ generation. Taken together, HCN1 is proposed to play
an important role in the molecular linkage between epileptic seizures and Aβ generation,
and in the aggravation of sporadic AD.'
author:
- first_name: Yuhki
full_name: Saito, Yuhki
last_name: Saito
- first_name: Tsuyoshi
full_name: Inoue, Tsuyoshi
last_name: Inoue
- first_name: Gang
full_name: Zhu, Gang
last_name: Zhu
- first_name: Naoki
full_name: Kimura, Naoki
last_name: Kimura
- first_name: Motohiro
full_name: Okada, Motohiro
last_name: Okada
- first_name: Masaki
full_name: Nishimura, Masaki
last_name: Nishimura
- first_name: Shigeo
full_name: Murayama, Shigeo
last_name: Murayama
- first_name: Sunao
full_name: Kaneko, Sunao
last_name: Kaneko
- first_name: Ryuichi
full_name: Ryuichi Shigemoto
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Keiji
full_name: Imoto, Keiji
last_name: Imoto
- first_name: Toshiharu
full_name: Suzuki, Toshiharu
last_name: Suzuki
citation:
ama: 'Saito Y, Inoue T, Zhu G, et al. Hyperpolarization-activated cyclic nucleotide
gated channels: A potential molecular link between epileptic seizures and Aβ generation
in Alzheimer’s disease. Molecular Neurodegeneration. 2012;7(1). doi:10.1186/1750-1326-7-50'
apa: 'Saito, Y., Inoue, T., Zhu, G., Kimura, N., Okada, M., Nishimura, M., … Suzuki,
T. (2012). Hyperpolarization-activated cyclic nucleotide gated channels: A potential
molecular link between epileptic seizures and Aβ generation in Alzheimer’s disease.
Molecular Neurodegeneration. BioMed Central. https://doi.org/10.1186/1750-1326-7-50'
chicago: 'Saito, Yuhki, Tsuyoshi Inoue, Gang Zhu, Naoki Kimura, Motohiro Okada,
Masaki Nishimura, Shigeo Murayama, et al. “Hyperpolarization-Activated Cyclic
Nucleotide Gated Channels: A Potential Molecular Link between Epileptic Seizures
and Aβ Generation in Alzheimer’s Disease.” Molecular Neurodegeneration.
BioMed Central, 2012. https://doi.org/10.1186/1750-1326-7-50.'
ieee: 'Y. Saito et al., “Hyperpolarization-activated cyclic nucleotide gated
channels: A potential molecular link between epileptic seizures and Aβ generation
in Alzheimer’s disease,” Molecular Neurodegeneration, vol. 7, no. 1. BioMed
Central, 2012.'
ista: 'Saito Y, Inoue T, Zhu G, Kimura N, Okada M, Nishimura M, Murayama S, Kaneko
S, Shigemoto R, Imoto K, Suzuki T. 2012. Hyperpolarization-activated cyclic nucleotide
gated channels: A potential molecular link between epileptic seizures and Aβ generation
in Alzheimer’s disease. Molecular Neurodegeneration. 7(1).'
mla: 'Saito, Yuhki, et al. “Hyperpolarization-Activated Cyclic Nucleotide Gated
Channels: A Potential Molecular Link between Epileptic Seizures and Aβ Generation
in Alzheimer’s Disease.” Molecular Neurodegeneration, vol. 7, no. 1, BioMed
Central, 2012, doi:10.1186/1750-1326-7-50.'
short: Y. Saito, T. Inoue, G. Zhu, N. Kimura, M. Okada, M. Nishimura, S. Murayama,
S. Kaneko, R. Shigemoto, K. Imoto, T. Suzuki, Molecular Neurodegeneration 7 (2012).
date_created: 2018-12-11T11:57:53Z
date_published: 2012-10-03T00:00:00Z
date_updated: 2021-01-12T06:57:42Z
day: '03'
doi: 10.1186/1750-1326-7-50
extern: 1
intvolume: ' 7'
issue: '1'
month: '10'
publication: Molecular Neurodegeneration
publication_status: published
publisher: BioMed Central
publist_id: '4426'
quality_controlled: 0
status: public
title: 'Hyperpolarization-activated cyclic nucleotide gated channels: A potential
molecular link between epileptic seizures and Aβ generation in Alzheimer''s disease'
type: journal_article
volume: 7
year: '2012'
...
---
_id: '2477'
abstract:
- lang: eng
text: Dynamic activity of glia has repeatedly been demonstrated, but if such activity
is independent from neuronal activity, glia would not have any role in the information
processing in the brain or in the generation of animal behavior. Evidence for
neurons communicating with glia is solid, but the signaling pathway leading back
from glial-to-neuronal activity was often difficult to study. Here, we introduced
a transgenic mouse line in which channelrhodopsin-2, a light-gated cation channel,
was expressed in astrocytes. Selective photostimulation of these astrocytes in
vivo triggered neuronal activation. Using slice preparations, we show that glial
photostimulation leads to release of glutamate, which was sufficient to activate
AMPA receptors on Purkinje cells and to induce long-term depression of parallel
fiber-to-Purkinje cell synapses through activation of metabotropic glutamate receptors.
In contrast to neuronal synaptic vesicular release, glial activation likely causes
preferential activation of extrasynaptic receptors that appose glial membrane.
Finally, we show that neuronal activation by glial stimulation can lead to perturbation
of cerebellar modulated motor behavior. These findings demonstrate that glia can
modulate the tone of neuronal activity and behavior. This animal model is expected
to be a potentially powerful approach to study the role of glia in brain function.
author:
- first_name: Takuya
full_name: Sasaki, Takuya
last_name: Sasaki
- first_name: Kaoru
full_name: Beppu, Kaoru
last_name: Beppu
- first_name: Kenji
full_name: Tanaka, Kenji F
last_name: Tanaka
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Ryuichi
full_name: Ryuichi Shigemoto
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: Ko
full_name: Matsui, Ko
last_name: Matsui
citation:
ama: Sasaki T, Beppu K, Tanaka K, Fukazawa Y, Shigemoto R, Matsui K. Application
of an optogenetic byway for perturbing neuronal activity via glial photostimulation.
PNAS. 2012;109(50):20720-20725. doi:10.1073/pnas.1213458109
apa: Sasaki, T., Beppu, K., Tanaka, K., Fukazawa, Y., Shigemoto, R., & Matsui,
K. (2012). Application of an optogenetic byway for perturbing neuronal activity
via glial photostimulation. PNAS. National Academy of Sciences. https://doi.org/10.1073/pnas.1213458109
chicago: Sasaki, Takuya, Kaoru Beppu, Kenji Tanaka, Yugo Fukazawa, Ryuichi Shigemoto,
and Ko Matsui. “Application of an Optogenetic Byway for Perturbing Neuronal Activity
via Glial Photostimulation.” PNAS. National Academy of Sciences, 2012.
https://doi.org/10.1073/pnas.1213458109.
ieee: T. Sasaki, K. Beppu, K. Tanaka, Y. Fukazawa, R. Shigemoto, and K. Matsui,
“Application of an optogenetic byway for perturbing neuronal activity via glial
photostimulation,” PNAS, vol. 109, no. 50. National Academy of Sciences,
pp. 20720–20725, 2012.
ista: Sasaki T, Beppu K, Tanaka K, Fukazawa Y, Shigemoto R, Matsui K. 2012. Application
of an optogenetic byway for perturbing neuronal activity via glial photostimulation.
PNAS. 109(50), 20720–20725.
mla: Sasaki, Takuya, et al. “Application of an Optogenetic Byway for Perturbing
Neuronal Activity via Glial Photostimulation.” PNAS, vol. 109, no. 50,
National Academy of Sciences, 2012, pp. 20720–25, doi:10.1073/pnas.1213458109.
short: T. Sasaki, K. Beppu, K. Tanaka, Y. Fukazawa, R. Shigemoto, K. Matsui, PNAS
109 (2012) 20720–20725.
date_created: 2018-12-11T11:57:54Z
date_published: 2012-12-11T00:00:00Z
date_updated: 2021-01-12T06:57:43Z
day: '11'
doi: 10.1073/pnas.1213458109
extern: 1
intvolume: ' 109'
issue: '50'
month: '12'
page: 20720 - 20725
publication: PNAS
publication_status: published
publisher: National Academy of Sciences
publist_id: '4424'
quality_controlled: 0
status: public
title: Application of an optogenetic byway for perturbing neuronal activity via glial
photostimulation
type: journal_article
volume: 109
year: '2012'
...
---
_id: '2474'
abstract:
- lang: eng
text: 'Interneurons are critical for neuronal circuit function, but how their dendritic
morphologies and membrane properties influence information flow within neuronal
circuits is largely unknown. We studied the spatiotemporal profile of synaptic
integration and short-term plasticity in dendrites of mature cerebellar stellate
cells by combining two-photon guided electrical stimulation, glutamate uncaging,
electron microscopy, and modeling. Synaptic activation within thin (0.4 μm) dendrites
produced somatic responses that became smaller and slower with increasing distance
from the soma, sublinear subthreshold input-output relationships, and a somatodendritic
gradient of short-term plasticity. Unlike most studies showing that neurons employ
active dendritic mechanisms, we found that passive cable properties of thin dendrites
determine the sublinear integration and plasticity gradient, which both result
from large dendritic depolarizations that reduce synaptic driving force. These
integrative properties allow stellate cells to act as spatiotemporal filters of
synaptic input patterns, thereby biasing their output in favor of sparse presynaptic
activity. Stellate cells are critical sources of inhibition in the cerebellum,
but how their dendrites integrate excitatory synaptic inputs is unknown. Abrahamsson
et al. show that thin dendrites and passive membrane properties of SCs promote
sublinear synaptic summation and distance-dependent short-term plasticity. '
author:
- first_name: Therese
full_name: Abrahamsson, Therese
last_name: Abrahamsson
- first_name: Laurence
full_name: Cathala, Laurence
last_name: Cathala
- first_name: Ko
full_name: Matsui, Ko
last_name: Matsui
- first_name: Ryuichi
full_name: Ryuichi Shigemoto
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: David
full_name: DiGregorio, David A
last_name: Digregorio
citation:
ama: Abrahamsson T, Cathala L, Matsui K, Shigemoto R, Digregorio D. Thin dendrites
of cerebellar interneurons confer sublinear synaptic integration and a gradient
of short-term plasticity. Neuron. 2012;73(6):1159-1172. doi:10.1016/j.neuron.2012.01.027
apa: Abrahamsson, T., Cathala, L., Matsui, K., Shigemoto, R., & Digregorio,
D. (2012). Thin dendrites of cerebellar interneurons confer sublinear synaptic
integration and a gradient of short-term plasticity. Neuron. Elsevier.
https://doi.org/10.1016/j.neuron.2012.01.027
chicago: Abrahamsson, Therese, Laurence Cathala, Ko Matsui, Ryuichi Shigemoto, and
David Digregorio. “Thin Dendrites of Cerebellar Interneurons Confer Sublinear
Synaptic Integration and a Gradient of Short-Term Plasticity.” Neuron.
Elsevier, 2012. https://doi.org/10.1016/j.neuron.2012.01.027.
ieee: T. Abrahamsson, L. Cathala, K. Matsui, R. Shigemoto, and D. Digregorio, “Thin
dendrites of cerebellar interneurons confer sublinear synaptic integration and
a gradient of short-term plasticity,” Neuron, vol. 73, no. 6. Elsevier,
pp. 1159–1172, 2012.
ista: Abrahamsson T, Cathala L, Matsui K, Shigemoto R, Digregorio D. 2012. Thin
dendrites of cerebellar interneurons confer sublinear synaptic integration and
a gradient of short-term plasticity. Neuron. 73(6), 1159–1172.
mla: Abrahamsson, Therese, et al. “Thin Dendrites of Cerebellar Interneurons Confer
Sublinear Synaptic Integration and a Gradient of Short-Term Plasticity.” Neuron,
vol. 73, no. 6, Elsevier, 2012, pp. 1159–72, doi:10.1016/j.neuron.2012.01.027.
short: T. Abrahamsson, L. Cathala, K. Matsui, R. Shigemoto, D. Digregorio, Neuron
73 (2012) 1159–1172.
date_created: 2018-12-11T11:57:52Z
date_published: 2012-03-22T00:00:00Z
date_updated: 2021-01-12T06:57:42Z
day: '22'
doi: 10.1016/j.neuron.2012.01.027
extern: 1
intvolume: ' 73'
issue: '6'
month: '03'
page: 1159 - 1172
publication: Neuron
publication_status: published
publisher: Elsevier
publist_id: '4427'
quality_controlled: 0
status: public
title: Thin dendrites of cerebellar interneurons confer sublinear synaptic integration
and a gradient of short-term plasticity
type: journal_article
volume: 73
year: '2012'
...
---
_id: '2515'
abstract:
- lang: eng
text: We investigated the temporal and spatial expression of SK2 in the developing
mouse hippocampus using molecular and biochemical techniques, quantitative immunogold
electron microscopy, and electrophysiology. The mRNA encoding SK2 was expressed
in the developing and adult hippocampus. Western blotting and immunohistochemistry
showed that SK2 protein increased with age. This was accompanied by a shift in
subcellular localization. Early in development (P5), SK2 was predominantly localized
to the endoplasmic reticulum in the pyramidal cell layer. But by P30 SK2 was almost
exclusively expressed in the dendrites and spines. The level of SK2 at the postsynaptic
density (PSD) also increased during development. In the adult, SK2 expression
on the spine plasma membrane showed a proximal-to-distal gradient. Consistent
with this redistribution and gradient of SK2, the selective SK channel blocker
apamin increased evoked excitatory postsynaptic potentials (EPSPs) only in CA1
pyramidal neurons from mice older than P15. However, the effect of apamin on EPSPs
was not different between synapses in proximal or distal stratum radiatum or stratum
lacunosum-moleculare in adult. These results show a developmental increase and
gradient in SK2-containing channel surface expression that underlie their influence
on neurotransmission, and that may contribute to increased memory acquisition
during early development.
author:
- first_name: Carmen
full_name: Ballesteros-Merino, Carmen
last_name: Ballesteros Merino
- first_name: Michael
full_name: Lin, Michael
last_name: Lin
- first_name: Wendy
full_name: Wu, Wendy W
last_name: Wu
- first_name: Clotilde
full_name: Ferrándiz-Huertas, Clotilde
last_name: Ferrándiz Huertas
- first_name: María
full_name: Cabañero, María José
last_name: Cabañero
- first_name: Masahiko
full_name: Watanabe, Masahiko
last_name: Watanabe
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Ryuichi
full_name: Ryuichi Shigemoto
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
- first_name: James
full_name: Maylie, James G
last_name: Maylie
- first_name: John
full_name: Adelman, John P
last_name: Adelman
- first_name: Rafael
full_name: Luján, Rafael
last_name: Luján
citation:
ama: Ballesteros Merino C, Lin M, Wu W, et al. Developmental profile of SK2 channel
expression and function in CA1 neurons. Hippocampus. 2012;22(6):1467-1480.
doi:10.1002/hipo.20986
apa: Ballesteros Merino, C., Lin, M., Wu, W., Ferrándiz Huertas, C., Cabañero, M.,
Watanabe, M., … Luján, R. (2012). Developmental profile of SK2 channel expression
and function in CA1 neurons. Hippocampus. Wiley-Blackwell. https://doi.org/10.1002/hipo.20986
chicago: Ballesteros Merino, Carmen, Michael Lin, Wendy Wu, Clotilde Ferrándiz Huertas,
María Cabañero, Masahiko Watanabe, Yugo Fukazawa, et al. “ Developmental Profile
of SK2 Channel Expression and Function in CA1 Neurons.” Hippocampus. Wiley-Blackwell,
2012. https://doi.org/10.1002/hipo.20986.
ieee: C. Ballesteros Merino et al., “ Developmental profile of SK2 channel
expression and function in CA1 neurons,” Hippocampus, vol. 22, no. 6. Wiley-Blackwell,
pp. 1467–1480, 2012.
ista: Ballesteros Merino C, Lin M, Wu W, Ferrándiz Huertas C, Cabañero M, Watanabe
M, Fukazawa Y, Shigemoto R, Maylie J, Adelman J, Luján R. 2012. Developmental
profile of SK2 channel expression and function in CA1 neurons. Hippocampus. 22(6),
1467–1480.
mla: Ballesteros Merino, Carmen, et al. “ Developmental Profile of SK2 Channel Expression
and Function in CA1 Neurons.” Hippocampus, vol. 22, no. 6, Wiley-Blackwell,
2012, pp. 1467–80, doi:10.1002/hipo.20986.
short: C. Ballesteros Merino, M. Lin, W. Wu, C. Ferrándiz Huertas, M. Cabañero,
M. Watanabe, Y. Fukazawa, R. Shigemoto, J. Maylie, J. Adelman, R. Luján, Hippocampus
22 (2012) 1467–1480.
date_created: 2018-12-11T11:58:07Z
date_published: 2012-06-01T00:00:00Z
date_updated: 2021-01-12T06:57:57Z
day: '01'
doi: 10.1002/hipo.20986
extern: 1
intvolume: ' 22'
issue: '6'
month: '06'
page: 1467 - 1480
publication: Hippocampus
publication_status: published
publisher: Wiley-Blackwell
publist_id: '4386'
quality_controlled: 0
status: public
title: ' Developmental profile of SK2 channel expression and function in CA1 neurons'
type: journal_article
volume: 22
year: '2012'
...
---
_id: '2514'
abstract:
- lang: eng
text: Visual information must be relayed through the lateral geniculate nucleus
before it reaches the visual cortex. However, not all spikes created in the retina
lead to postsynaptic spikes and properties of the retinogeniculate synapse contribute
to this filtering. To understand the mechanisms underlying this filtering process,
we conducted electrophysiology to assess the properties of signal transmission
in the Long-Evans rat. We also performed SDS-digested freeze-fracture replica
labeling to quantify the receptor and transporter distribution, as well as EM
reconstruction to describe the 3D structure. To analyze the impact of transmitter
diffusion on the activity of the receptors, simulations were integrated. We identified
that a large contributor to the filtering is the marked paired-pulse depression
at this synapse, which was intensified by the morphological characteristics of
the contacts. The broad presynaptic and postsynaptic contact area restricts transmitter
diffusion two dimensionally. Additionally, the presence of multiple closely arranged
release sites invites intersynaptic spillover, which causes desensitization of
AMPA receptors. The presence of AMPA receptors that slowly recover from desensitization
along with the high presynaptic release probability and multivesicular release
at each synapse also contribute to the depression. These features contrast with
many other synapses where spatiotemporal spread of transmitter is limited by rapid
transmitter clearance allowing synapses to operate more independently. We propose
that the micrometer-order structure can ultimately affect the visual information
processing.
author:
- first_name: Timotheus
full_name: Budisantoso, Timotheus
last_name: Budisantoso
- first_name: Ko
full_name: Matsui, Ko
last_name: Matsui
- first_name: Naomi
full_name: Kamasawa, Naomi
last_name: Kamasawa
- first_name: Yugo
full_name: Fukazawa, Yugo
last_name: Fukazawa
- first_name: Ryuichi
full_name: Ryuichi Shigemoto
id: 499F3ABC-F248-11E8-B48F-1D18A9856A87
last_name: Shigemoto
orcid: 0000-0001-8761-9444
citation:
ama: Budisantoso T, Matsui K, Kamasawa N, Fukazawa Y, Shigemoto R. Mechanisms underlying
signal filtering at a multisynapse contact. Journal of Neuroscience. 2012;32(7):2357-2376.
doi:10.1523/JNEUROSCI.5243-11.2012
apa: Budisantoso, T., Matsui, K., Kamasawa, N., Fukazawa, Y., & Shigemoto, R.
(2012). Mechanisms underlying signal filtering at a multisynapse contact. Journal
of Neuroscience. Society for Neuroscience. https://doi.org/10.1523/JNEUROSCI.5243-11.2012
chicago: Budisantoso, Timotheus, Ko Matsui, Naomi Kamasawa, Yugo Fukazawa, and Ryuichi
Shigemoto. “Mechanisms Underlying Signal Filtering at a Multisynapse Contact.”
Journal of Neuroscience. Society for Neuroscience, 2012. https://doi.org/10.1523/JNEUROSCI.5243-11.2012.
ieee: T. Budisantoso, K. Matsui, N. Kamasawa, Y. Fukazawa, and R. Shigemoto, “Mechanisms
underlying signal filtering at a multisynapse contact,” Journal of Neuroscience,
vol. 32, no. 7. Society for Neuroscience, pp. 2357–2376, 2012.
ista: Budisantoso T, Matsui K, Kamasawa N, Fukazawa Y, Shigemoto R. 2012. Mechanisms
underlying signal filtering at a multisynapse contact. Journal of Neuroscience.
32(7), 2357–2376.
mla: Budisantoso, Timotheus, et al. “Mechanisms Underlying Signal Filtering at a
Multisynapse Contact.” Journal of Neuroscience, vol. 32, no. 7, Society
for Neuroscience, 2012, pp. 2357–76, doi:10.1523/JNEUROSCI.5243-11.2012.
short: T. Budisantoso, K. Matsui, N. Kamasawa, Y. Fukazawa, R. Shigemoto, Journal
of Neuroscience 32 (2012) 2357–2376.
date_created: 2018-12-11T11:58:07Z
date_published: 2012-02-15T00:00:00Z
date_updated: 2021-01-12T06:57:57Z
day: '15'
doi: 10.1523/JNEUROSCI.5243-11.2012
extern: 1
intvolume: ' 32'
issue: '7'
month: '02'
page: 2357 - 2376
publication: Journal of Neuroscience
publication_status: published
publisher: Society for Neuroscience
publist_id: '4387'
quality_controlled: 0
status: public
title: Mechanisms underlying signal filtering at a multisynapse contact
type: journal_article
volume: 32
year: '2012'
...