The Experts below are selected from a list of 2391 Experts worldwide ranked by ideXlab platform
Masanobu Kano - One of the best experts on this subject based on the ideXlab platform.
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modular organization of cerebellar Climbing Fiber inputs during goal directed behavior
eLife, 2019Co-Authors: Shinichiro Tsutsumi, Kenji Sakimura, Masanobu Kano, Kazuo Kitamura, Naoki Hidaka, Yoshikazu Isomura, Masanori MatsuzakiAbstract:The cerebellum has a parasagittal modular architecture characterized by precisely organized Climbing Fiber (CF) projections that are congruent with alternating aldolase C/zebrin II expression. However, the behavioral relevance of CF inputs into individual modules remains poorly understood. Here, we used two-photon calcium imaging in the cerebellar hemisphere Crus II in mice performing an auditory go/no-go task to investigate the functional differences in CF inputs to modules. CF signals in medial modules show anticipatory decreases, early increases, secondary increases, and reward-related increases or decreases, which represent quick motor initiation, go cues, fast motor behavior, and positive reward outcomes. CF signals in lateral modules show early increases and reward-related decreases, which represent no-go and/or go cues and positive reward outcomes. The boundaries of CF functions broadly correspond to those of aldolase C patterning. These results indicate that spatially segregated CF inputs in different modules play distinct roles in the execution of goal-directed behavior.
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maturation of cerebellar purkinje cell population activity during postnatal refinement of Climbing Fiber network
Cell Reports, 2017Co-Authors: Jeanmarc Good, Kenji Sakimura, Kazuo Kitamura, Masahiko Watanabe, Michael Mahoney, Taisuke Miyazaki, Kenji F Tanaka, Masanobu KanoAbstract:Summary Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the Climbing Fiber (CF) to Purkinje cell (PC) network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity.
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activity dependent gating of calcium spikes by a type k channels controls Climbing Fiber signaling in purkinje cell dendrites
Neuron, 2014Co-Authors: Yo Otsu, Masanobu Kano, Paikan Marcaggi, Anne Feltz, Philippe Isope, Mihaly Kollo, Zoltan Nusser, Benjamin Mathieu, Mika Tsujita, Kenji SakimuraAbstract:In cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal Climbing Fiber (CF) input controls plasticity at distal parallel Fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules.
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influence of parallel Fiber purkinje cell synapse formation on postnatal development of Climbing Fiber purkinje cell synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Takayuki Yoshida, Masayoshi Mishina, Masanobu Kano, Masahiko WatanabeAbstract:Abstract The Climbing Fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with “hypogranular” cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel Fibers (PFs), and normal formation of PF–PC synapses. Our understanding of how PF–PC synapse formation affects development of CF–PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor δ2 subunit (GluRδ2), an orphan receptor expressed selectively in PCs. Deletion of GluRδ2 results in impairment of PF–PC synapse formation, which leads to defects in development of CF–PC synapses. In this article, we review how impaired PF–PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRδ2 knockout mice. We propose a new scheme that CF–PC synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, “early phase” of CF synapse elimination from P7 to around P11, and “late phase” of CF synapse elimination from around P12. Normal PF–PC synapse formation is required for the “late phase” of CF synapse elimination.
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influence of parallel Fiber purkinje cell synapse formation on postnatal development of Climbing Fiber purkinje cell synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Masayoshi Mishina, Masanobu Kano, Masahiko Watanabe, Tomoyuki YoshidaAbstract:The Climbing Fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with "hypogranular" cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel Fibers (PFs), and normal formation of PF-PC synapses. Our understanding of how PF-PC synapse formation affects development of CF-PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor delta2 subunit (GluRdelta2), an orphan receptor expressed selectively in PCs. Deletion of GluRdelta2 results in impairment of PF-PC synapse formation, which leads to defects in development of CF-PC synapses. In this article, we review how impaired PF-PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRdelta2 knockout mice. We propose a new scheme that CF-PC synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, "early phase" of CF synapse elimination from P7 to around P11, and "late phase" of CF synapse elimination from around P12. Normal PF-PC synapse formation is required for the "late phase" of CF synapse elimination.
Masahiko Watanabe - One of the best experts on this subject based on the ideXlab platform.
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maturation of cerebellar purkinje cell population activity during postnatal refinement of Climbing Fiber network
Cell Reports, 2017Co-Authors: Jeanmarc Good, Kenji Sakimura, Kazuo Kitamura, Masahiko Watanabe, Michael Mahoney, Taisuke Miyazaki, Kenji F Tanaka, Masanobu KanoAbstract:Summary Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the Climbing Fiber (CF) to Purkinje cell (PC) network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity.
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type 2 k cl cotransporter is preferentially recruited to Climbing Fiber synapses during development and the stellate cell targeting dendritic zone at adulthood in cerebellar purkinje cells
European Journal of Neuroscience, 2013Co-Authors: Issei Kawakita, Taisuke Miyazaki, Motokazu Uchigashima, Kohtarou Konno, Miwako Yamasaki, Masahiko WatanabeAbstract:Postnatal expression of the type 2 K(+) -Cl(-) cotransporter (KCC2) in neurons lowers the Cl(-) equilibrium potential to values that are more negative than the resting potential, thereby converting the action of Cl(-) -permeable GABA(A) and glycine receptors from excitatory to inhibitory. In the present study, we investigated the spatiotemporal expression of KCC2 in mouse cerebella, particularly focusing on Purkinje cells (PCs). First, we confirmed the fundamental expression profiles of KCC2 in the cerebellum, i.e. neuron-specific expression, somatodendritic distribution, and postnatal upregulation. We also found preferential recruitment to Climbing Fiber (CF) synapses during the second and third postnatal weeks, when perisomatic innervation in PCs switches from CFs to basket cell axons (BAs) and also when single winner CFs translocate from somata to dendrites. In parallel with this synaptic recruitment, the intracellular distribution shifted from a diffuse cytoplasmic to a predominantly cell surface pattern. In adult PCs, CF synapse-associated accumulation was obscured. Instead, significantly high expression was noted on the surface of PC dendrites in the superficial two-thirds of the molecular layer, in which stellate cells reside and project axons to innervate PC dendrites. Thus, the somatodendritic distribution in PCs is regulated in relation to particular inputs or input zones. During development, timed recruitment of KCC2 to CF synapses will augment inhibitory GABAergic actions by incoming BAs, promoting the CF-to-BA switchover in perisomatic PC innervation. In adulthood, enriched KCC2 expression at the stellate cell-targeting territory of PC dendrites might help in maintaining intracellular Cl(-) homeostasis and the polarity of GABA(A) receptor-mediated responses upon sustained activity of this interneuron.
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influence of parallel Fiber purkinje cell synapse formation on postnatal development of Climbing Fiber purkinje cell synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Takayuki Yoshida, Masayoshi Mishina, Masanobu Kano, Masahiko WatanabeAbstract:Abstract The Climbing Fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with “hypogranular” cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel Fibers (PFs), and normal formation of PF–PC synapses. Our understanding of how PF–PC synapse formation affects development of CF–PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor δ2 subunit (GluRδ2), an orphan receptor expressed selectively in PCs. Deletion of GluRδ2 results in impairment of PF–PC synapse formation, which leads to defects in development of CF–PC synapses. In this article, we review how impaired PF–PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRδ2 knockout mice. We propose a new scheme that CF–PC synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, “early phase” of CF synapse elimination from P7 to around P11, and “late phase” of CF synapse elimination from around P12. Normal PF–PC synapse formation is required for the “late phase” of CF synapse elimination.
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influence of parallel Fiber purkinje cell synapse formation on postnatal development of Climbing Fiber purkinje cell synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Masayoshi Mishina, Masanobu Kano, Masahiko Watanabe, Tomoyuki YoshidaAbstract:The Climbing Fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with "hypogranular" cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel Fibers (PFs), and normal formation of PF-PC synapses. Our understanding of how PF-PC synapse formation affects development of CF-PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor delta2 subunit (GluRdelta2), an orphan receptor expressed selectively in PCs. Deletion of GluRdelta2 results in impairment of PF-PC synapse formation, which leads to defects in development of CF-PC synapses. In this article, we review how impaired PF-PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRdelta2 knockout mice. We propose a new scheme that CF-PC synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, "early phase" of CF synapse elimination from P7 to around P11, and "late phase" of CF synapse elimination from around P12. Normal PF-PC synapse formation is required for the "late phase" of CF synapse elimination.
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effects of fak ablation on cerebellar foliation bergmann glia positioning and Climbing Fiber territory on purkinje cells
European Journal of Neuroscience, 2008Co-Authors: Fumihiro Watanabe, Kenji Sakimura, Masahiko Watanabe, Taisuke Miyazaki, Tomonori Takeuchi, Masahiro Fukaya, Takanori Nomura, Shigeru Noguchi, Hisashi Mori, Masayoshi MishinaAbstract:Focal adhesion kinase (FAK) is a non-receptor tyrosine kinase that is widely expressed in the brain, and plays key roles in various cellular processes in response to both extracellular and intracellular stimuli. Here, we explored the role of FAK in cerebellar development. In the mouse cerebellum, FAK was found to be distributed as tiny cytoplasmic aggregates in various neuronal and glial elements, including Purkinje cells (PCs), Bergmann glia (BG), parallel Fiber (PF)-terminals and Climbing Fiber (CF)-terminals. The neuron/glia-specific ablation of FAK impaired cerebellar foliation, such as variable decreases in foliation sizes and the lack of intercrural and precentral fissures. Some of the BG cells became situated ectopically in the molecular layer. Furthermore, the FAK ablation altered the innervation territories of CFs and PFs on PCs. CF innervation regressed to the basal portion of proximal dendrites and somata, whereas ectopic spines protruded from proximal dendrites and PFs expanded their territory by innervating the ectopic spines. Furthermore, the persistence of surplus CFs innervating PC somata caused multiple innervation. When FAK was selectively ablated in PCs, diminished dendritic innervation and persistent somatic innervation by CFs were observed, whereas cerebellar foliation and cell positioning of BG were normally retained. These results suggest that FAK in various neuronal and glial elements is required for the formation of normal histoarchitecture and cytoarchitecture in the cerebellum, and for the construction of proper innervation territory and synaptic wiring in PCs.
Kouichi Hashimoto - One of the best experts on this subject based on the ideXlab platform.
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influence of parallel Fiber purkinje cell synapse formation on postnatal development of Climbing Fiber purkinje cell synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Takayuki Yoshida, Masayoshi Mishina, Masanobu Kano, Masahiko WatanabeAbstract:Abstract The Climbing Fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with “hypogranular” cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel Fibers (PFs), and normal formation of PF–PC synapses. Our understanding of how PF–PC synapse formation affects development of CF–PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor δ2 subunit (GluRδ2), an orphan receptor expressed selectively in PCs. Deletion of GluRδ2 results in impairment of PF–PC synapse formation, which leads to defects in development of CF–PC synapses. In this article, we review how impaired PF–PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRδ2 knockout mice. We propose a new scheme that CF–PC synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, “early phase” of CF synapse elimination from P7 to around P11, and “late phase” of CF synapse elimination from around P12. Normal PF–PC synapse formation is required for the “late phase” of CF synapse elimination.
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influence of parallel Fiber purkinje cell synapse formation on postnatal development of Climbing Fiber purkinje cell synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Masayoshi Mishina, Masanobu Kano, Masahiko Watanabe, Tomoyuki YoshidaAbstract:The Climbing Fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with "hypogranular" cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel Fibers (PFs), and normal formation of PF-PC synapses. Our understanding of how PF-PC synapse formation affects development of CF-PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor delta2 subunit (GluRdelta2), an orphan receptor expressed selectively in PCs. Deletion of GluRdelta2 results in impairment of PF-PC synapse formation, which leads to defects in development of CF-PC synapses. In this article, we review how impaired PF-PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRdelta2 knockout mice. We propose a new scheme that CF-PC synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, "early phase" of CF synapse elimination from P7 to around P11, and "late phase" of CF synapse elimination from around P12. Normal PF-PC synapse formation is required for the "late phase" of CF synapse elimination.
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diminished Climbing Fiber innervation of purkinje cells in the cerebellum of myosin va mutant mice and rats
Developmental Neurobiology, 2007Co-Authors: Yoshiko Takagishi, Kouichi Hashimoto, Masanobu Kano, Masahiko Watanabe, Tetsuro Kayahara, Hiroyuki Otsuka, Akira Mizoguchi, Yoshiharu MurataAbstract:Myosin Va is an actin-based molecular motor that is involved in organelle transport and membrane trafficking. Here, we explored the role of myosin Va in the formation of synaptic circuitry by examining Climbing Fiber (CF) innervation of Purkinje cells (PCs) in the cerebella of dilute-neurological (d-n) mice and dilute-opisthotonus (dop) rats that have mutations in dilute-encoded myosin Va. Anterograde labeling of CFs with biotinylated dextran amine (BDA) revealed that they arborized poorly and that their tips extended only half way through the thickness of the molecular layer (ML) in adult d-n mice. Using immunohistochemistry specific for vesicular glutamate transporter 2 (VGluT2) to visualize CF synaptic terminals, we found that during development and in adulthood, these terminals did not ascend as far along the proximal shaft dendrites of PCs in d-n mice and dop rats as they did in normal animals. An irregular distribution of BDA-labeled bulbous varicosities and VGluT2 spots along CF branches were also noted in these animals. Finally, VGluT2-positive CF terminals were occasionally localized on the PC somata of adult d-n cerebella. These phenotypes are consistent with our electrophysiological findings that CF-mediated excitatory postsynaptic currents (EPSCs) were significantly smaller in amplitude and faster in decay in adult d-n mice, and that the regression of multiple CFs was slightly delayed in developing d-n mice. Taken together, our results suggest that myosin Va is essential for terminal CF extension and for the establishment of CF synapses within the proper dendritic territories of PCs. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.
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postnatal development and synapse elimination of Climbing Fiber to purkinje cell projection in the cerebellum
Neuroscience Research, 2005Co-Authors: Kouichi Hashimoto, Masanobu KanoAbstract:Cerebellar Climbing Fiber (CF) to Purkinje cell (PC) synapses in rodents provides a good model to study mechanisms underlying postnatal development of synaptic functions and elimination of redundant synapses in the central nervous system. At birth, each PC is innervated by multiple CFs. Then, single CF input is selected, matured and strengthened, while surplus CFs are eliminated. By the end of the third postnatal week, most PCs become innervated by single CFs. This up-date article aims to provide an overview of recent studies on the mechanisms of this process.
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functional differentiation of multiple Climbing Fiber inputs during synapse elimination in the developing cerebellum
Neuron, 2003Co-Authors: Kouichi Hashimoto, Masanobu KanoAbstract:Abstract We studied how physiological properties of cerebellar Climbing Fiber (CF) to Purkinje cell (PC) synapses change during developmental transition from multiple to mono CF innervation onto each PC. From P3 to P6, differences in the strengths of multiple CFs became larger. Around P10, each PC was either monoinnervated by one strong CF (CF-mono) or multiply innervated by one strong CF (CF-multi-S) plus a few weaker CFs (CF-multi-W). We show that simultaneous release of multiple vesicles per site occurs normally from CF-multi-S, CF-mono, and mature CFs, but less frequently from CF-multi-W and neonatal CFs. We also present evidence suggesting that weaker CFs with lower probability of multivesicular release would be withdrawn preferentially. The results suggest that differentiation into strong and weak CFs with high and low probabilities of multivesicular release precedes developmental CF synapse elimination.
Kenji Sakimura - One of the best experts on this subject based on the ideXlab platform.
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modular organization of cerebellar Climbing Fiber inputs during goal directed behavior
eLife, 2019Co-Authors: Shinichiro Tsutsumi, Kenji Sakimura, Masanobu Kano, Kazuo Kitamura, Naoki Hidaka, Yoshikazu Isomura, Masanori MatsuzakiAbstract:The cerebellum has a parasagittal modular architecture characterized by precisely organized Climbing Fiber (CF) projections that are congruent with alternating aldolase C/zebrin II expression. However, the behavioral relevance of CF inputs into individual modules remains poorly understood. Here, we used two-photon calcium imaging in the cerebellar hemisphere Crus II in mice performing an auditory go/no-go task to investigate the functional differences in CF inputs to modules. CF signals in medial modules show anticipatory decreases, early increases, secondary increases, and reward-related increases or decreases, which represent quick motor initiation, go cues, fast motor behavior, and positive reward outcomes. CF signals in lateral modules show early increases and reward-related decreases, which represent no-go and/or go cues and positive reward outcomes. The boundaries of CF functions broadly correspond to those of aldolase C patterning. These results indicate that spatially segregated CF inputs in different modules play distinct roles in the execution of goal-directed behavior.
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maturation of cerebellar purkinje cell population activity during postnatal refinement of Climbing Fiber network
Cell Reports, 2017Co-Authors: Jeanmarc Good, Kenji Sakimura, Kazuo Kitamura, Masahiko Watanabe, Michael Mahoney, Taisuke Miyazaki, Kenji F Tanaka, Masanobu KanoAbstract:Summary Neural circuits undergo massive refinements during postnatal development. In the developing cerebellum, the Climbing Fiber (CF) to Purkinje cell (PC) network is drastically reshaped by eliminating early-formed redundant CF to PC synapses. To investigate the impact of CF network refinement on PC population activity during postnatal development, we monitored spontaneous CF responses in neighboring PCs and the activity of populations of nearby CF terminals using in vivo two-photon calcium imaging. Population activity is highly synchronized in newborn mice, and the degree of synchrony gradually declines during the first postnatal week in PCs and, to a lesser extent, in CF terminals. Knockout mice lacking P/Q-type voltage-gated calcium channel or glutamate receptor δ2, in which CF network refinement is severely impaired, exhibit an abnormally high level of synchrony in PC population activity. These results suggest that CF network refinement is a structural basis for developmental desynchronization and maturation of PC population activity.
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activity dependent gating of calcium spikes by a type k channels controls Climbing Fiber signaling in purkinje cell dendrites
Neuron, 2014Co-Authors: Yo Otsu, Masanobu Kano, Paikan Marcaggi, Anne Feltz, Philippe Isope, Mihaly Kollo, Zoltan Nusser, Benjamin Mathieu, Mika Tsujita, Kenji SakimuraAbstract:In cerebellar Purkinje cell dendrites, heterosynaptic calcium signaling induced by the proximal Climbing Fiber (CF) input controls plasticity at distal parallel Fiber (PF) synapses. The substrate and regulation of this long-range dendritic calcium signaling are poorly understood. Using high-speed calcium imaging, we examine the role of active dendritic conductances. Under basal conditions, CF stimulation evokes T-type calcium signaling displaying sharp proximodistal decrement. Combined mGluR1 receptor activation and depolarization, two activity-dependent signals, unlock P/Q calcium spikes initiation and propagation, mediating efficient CF signaling at distal sites. These spikes are initiated in proximal smooth dendrites, independently from somatic sodium action potentials, and evoke high-frequency bursts of all-or-none fast-rising calcium transients in PF spines. Gradual calcium spike burst unlocking arises from increasing inactivation of mGluR1-modulated low-threshold A-type potassium channels located in distal dendrites. Evidence for graded activity-dependent CF calcium signaling at PF synapses refines current views on cerebellar supervised learning rules.
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influence of parallel Fiber purkinje cell synapse formation on postnatal development of Climbing Fiber purkinje cell synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Takayuki Yoshida, Masayoshi Mishina, Masanobu Kano, Masahiko WatanabeAbstract:Abstract The Climbing Fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with “hypogranular” cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel Fibers (PFs), and normal formation of PF–PC synapses. Our understanding of how PF–PC synapse formation affects development of CF–PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor δ2 subunit (GluRδ2), an orphan receptor expressed selectively in PCs. Deletion of GluRδ2 results in impairment of PF–PC synapse formation, which leads to defects in development of CF–PC synapses. In this article, we review how impaired PF–PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRδ2 knockout mice. We propose a new scheme that CF–PC synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, “early phase” of CF synapse elimination from P7 to around P11, and “late phase” of CF synapse elimination from around P12. Normal PF–PC synapse formation is required for the “late phase” of CF synapse elimination.
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influence of parallel Fiber purkinje cell synapse formation on postnatal development of Climbing Fiber purkinje cell synapses in the cerebellum
Neuroscience, 2009Co-Authors: Kouichi Hashimoto, Kenji Sakimura, Masayoshi Mishina, Masanobu Kano, Masahiko Watanabe, Tomoyuki YoshidaAbstract:The Climbing Fiber (CF) to Purkinje cell (PC) synapse in the cerebellum provides an ideal model for the study of developmental rearrangements of neural circuits. At birth, each PC is innervated by multiple CFs. These surplus CFs are eliminated during postnatal development, and mono innervation is attained by postnatal day 20 (P20) in mice. Earlier studies on spontaneous mutant mice and animals with "hypogranular" cerebella indicate that regression of surplus CFs requires normal generation of granule cells and their axons, parallel Fibers (PFs), and normal formation of PF-PC synapses. Our understanding of how PF-PC synapse formation affects development of CF-PC synapse has been greatly advanced by analyses of mutant mice deficient in glutamate receptor delta2 subunit (GluRdelta2), an orphan receptor expressed selectively in PCs. Deletion of GluRdelta2 results in impairment of PF-PC synapse formation, which leads to defects in development of CF-PC synapses. In this article, we review how impaired PF-PC synapse formation affects wiring of CFs to PCs based mostly on our data on GluRdelta2 knockout mice. We propose a new scheme that CF-PC synapses are shaped by the three consecutive events, namely functional differentiation of multiple CFs into one strong and a few weak inputs from P3 to P7, "early phase" of CF synapse elimination from P7 to around P11, and "late phase" of CF synapse elimination from around P12. Normal PF-PC synapse formation is required for the "late phase" of CF synapse elimination.
Christian Hansel - One of the best experts on this subject based on the ideXlab platform.
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Brief Communications Climbing Fiber-Evoked Endocannabinoid Signaling Heterosynaptically Suppresses
2016Co-Authors: Presynaptic Cerebellar, Long-term Potentiation, Boeke J. Van Beugen, Raghavendra Y. Nagaraja, Christian HanselAbstract:Endocannabinoid signaling has been demonstrated to mediate depolarization-induced suppression of excitation at Climbing Fiber (CF) and parallel Fiber (PF) synapses onto cerebellar Purkinje cells. Here, we show that CF-evoked release of cannabinoids (CBs) additionally suppresses a presynaptic form of long-term potentiation (LTP) at PF synapses. PF-LTP can be induced by 8 Hz PF tetanization but is blocked when the PF tetanization is paired with 4 or 1 Hz CF coactivation. CF activity can be substituted for by bath application of the CB receptor agonist WIN55,212-2 [R()-[2,3-dihydro-5-methyl-3-[(morpholinyl)methyl]pyrrolo[1,2,3-de]-1,4-benzoxazinyl]-(1-naphthalenyl) methanone]. In the presence of the CB1 receptor antagonist AM251 [N-1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-1-piperidinyl-1H-pyrazole-3-carboxamide], CF activity no longer suppresses PF-LTP. Presynaptic potentiation can also be obtained by the adenylyl cyclase activator forskolin. WIN55,212-2 blocked this forskolin-mediated enhancement, showing that CB1 receptor activation interferes with the adenylyl cyclase–protein kinase A cascade, which participates in LTP induction. CF activity has been described to promote the induction of postsynaptic PF-long-term depression (LTD) and to impair postsynaptic PF-LTP. Our observation that CF activity blocks the induction of presynaptic LTP suggests that the CF input controls all forms of presynaptic and postsynaptic PF plasticity and that CF activity provides a “safety lock ” to prevent an enhancement of transmitter release while postsyn-aptic AMPA receptor function is downregulated during LTD. Key words: cannabinoids; cerebellum; long-term depression; long-term potentiation; parallel Fiber; Purkinje cel
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Climbing Fiber triggered metabotropic slow potentials enhance dendritic calcium transients and simple spike firing in cerebellar purkinje cells
Molecular and Cellular Neuroscience, 2007Co-Authors: Qi Yuan, John T. Weber, Christian Hansel, Thomas KnopfelAbstract:Abstract Cerebellar Purkinje cells (PCs) receive synaptic input from numerous parallel Fibers (PFs) and from a single Climbing Fiber (CF). At both types of synapses, fast synaptic transmission is mediated by AMPA receptors, while at PF synapses burst activity can additionally recruit metabotropic glutamate receptors (mGluRs) that mediate a slow depolarizing potential. Here, we show that mGluR-activated slow potentials can be evoked throughout the dendrite by CF-evoked complex spike firing in the presence of an mGluR agonist. The CF-triggered mGluR potential was not only blocked by an mGluR antagonist but also when the CF-induced Ca 2+ transient was blocked by an AMPA receptor antagonist, suggesting the possibility that the slow potential can be activated by the simultaneous occurrence of agonist binding at mGluRs and a CF-evoked Ca 2+ transient. In turn, these CF-triggered slow mGluR potentials enhance the complex spike-associated calcium signals throughout the dendrite. Moreover, they provide a mechanism by which CFs can modulate the simple spike frequency of PCs.
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Bidirectional parallel Fiber plasticity in the cerebellum under Climbing Fiber control
Neuron, 2004Co-Authors: Michiel Coesmans, John T. Weber, Chris I De Zeeuw, Christian HanselAbstract:Cerebellar parallel Fiber (PF)-Purkinje cell (PC) synapses can undergo postsynaptically expressed long-term depression (LTD) or long-term potentiation (LTP) depending on whether or not the Climbing Fiber (CF) input is coactivated during tetanization. Here, we show that modifications of the postsynaptic calcium load using the calcium chelator BAPTA or photolytic calcium uncaging result in a reversal of the expected polarity of synaptic gain change. At higher concentrations, BAPTA blocks PF-LTP. These data indicate that PF-LTD requires a higher calcium threshold amplitude than PF-LTP induction and suggest that CF activity acts as a polarity switch by providing dendritic calcium transients. Moreover, previous CF-LTD induction changes the relative PF-LTD versus -LTP induction probability. These findings suggest that bidirectional cerebellar learning is governed by a calcium threshold rule operating "inverse" to the mechanism previously described at other glutamatergic synapses (BCM rule) and that the LTD/LTP induction probability is under heterosynaptic Climbing Fiber control.
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long term depression of Climbing Fiber evoked calcium transients in purkinje cell dendrites
Proceedings of the National Academy of Sciences of the United States of America, 2003Co-Authors: John T. Weber, Chris I De Zeeuw, David J Linden, Christian HanselAbstract:In recent years much has been learned about the molecular requirements for inducing long-term synaptic depression (LTD) in various brain regions. However, very little is known about the consequences of LTD induction for subsequent signaling events in postsynaptic neurons. We have addressed this issue by examining homosynaptic LTD at the cerebellar Climbing Fiber (CF)–Purkinje cell (PC) synapse. This synapse is built for reliable and massive excitation: Activation of a single axon produces an unusually large α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor-mediated synaptic current, the depolarization of which drives a regenerative complex spike producing a large, widespread Ca2+ transient in PC dendrites. Here we test whether CF LTD has an impact on dendritic, complex spike-evoked Ca2+ signals by simultaneously performing long-term recordings of complex spikes and microfluorimetric Ca2+ measurements in PC dendrites in rat cerebellar slices. Our data show that LTD of the CF excitatory postsynaptic current produces a reduction in both slow components of the complex spike waveform and complex spike-evoked dendritic Ca2+ transients. This LTD of dendritic Ca2+ signals may provide a neuroprotective mechanism and/or constitute “heterosynaptic metaplasticity” by reducing the probability for subsequent induction of those forms of use-dependent plasticity, which require CF-evoked Ca2+ signals such as parallel Fiber–PC LTD and interneuron–PC LTP.
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long term depression of the cerebellar Climbing Fiber purkinje neuron synapse
Neuron, 2000Co-Authors: Christian Hansel, David J LindenAbstract:In classic Marr-Albus-Ito models of cerebellar function, coactivation of the Climbing Fiber (CF) synapse, which provides massive, invariant excitation of Purkinje neurons (coding the unconditioned stimulus), together with a graded parallel Fiber synaptic array (coding the conditioned stimulus) leads to long-term depression (LTD) of parallel Fiber-Purkinje neuron synapses, underlying production of a conditioned response. Here, we show that the supposedly invariant CF synapse can also express LTD. Brief 5 Hz stimulation of the CF resulted in a sustained depression of CF EPSCs that did not spread to neighboring parallel Fiber synapses. Like parallel Fiber LTD, CF LTD required postsynaptic Ca2+ elevation, activation of group 1 mGluRs, and activation of PKC. CF LTD is potentially relevant for models of cerebellar motor control and learning and the developmental conversion from multiple to single CF innervation of Purkinje neurons.