--- _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' ...