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High-threshold voltage-gated Ca2+ channels may mediate capacitive Ca2+ entry in central neurons
S40
Abstracts / Neuroscience Research 58S (2007) S1–S244
O1P-EØ2 Nav1.1 predominantly localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in Nav1.1-deficient mice I. Ogiwara 1 , H. Miyamoto 2 , N. Morita 3 , N. Atapour 2 , E. Mazaki 1 , I. Inoue 1 , Y. Yanagawa 5 , K. Obata 4 , T. Furuichi 3 , T.K. Hensch 2 , K. Yamakawa 1 1 Laboratory of Neurogenetics, RIKEN-BSI, Japan; 2 Laboratory of Neuronal Circuit Development, RIKEN-BSI, Japan; 3 Laboratory for Molecular Neurogenesis, RIKEN-BSI, Japan; 4 Neuronal Circuit Mechanisms Research Group, RIKEN-BSI, Japan; 5 Department of Genetics and Behavioural Neuroscience, Gunma University and SORST, JST, Japan We have recently generated a Nav1.1-deficient mouse line and shown that these mutant mice developed epileptic seizures. We here report Nav1.1 localization in the developing neocortex and hippocampus. In neocortex, Nav1.1 is predominantly found at the axon initial segments (AISs) of parvalbumin-positive (PV) interneurons. Moreover, in mutant mice, trains of evoked action potentials in these PV, fast-spiking cells exhibited pronounced spike amplitude decrement late in the burst. In the hippocampus, Nav1.1 is predominantly distributed within AISs and somata of PV interneurons. Our data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice.
O1P-EØ5 Bral1, brain-specific link protein, is essential for stabilizing extracellular matrix at the node of Ranvier in the CNS Yoko Bekku, Yoshifumi Ninomiya, Toshitaka Oohashi Department of Molecular Biology & Biochemistry, Okayama University, Okayama, Japan Myelinated axons in the nervous system are organized into distinct domains with glial cell. The node of Ranvier ensures rapid propagation of the action potential along myelinated fibers. The hyaluronan binding chondroitin sulfate proteoglycans, called lecticans are the abundant ECM molecules in the brain. Brain link protein-1 (Bral1) is colocalized with versican V2, a lectican member, at the node of Ranvier in the CNS. In this study, we have generated Bral1-deficient mice via homologous recombination in embryonic stem cell. The formation and structure of myelin appeared normal. However, conduction velocity of the optic nerves of mutant mice showed about 20% decrease as compared with that of controls. Moreover, versican V2 and other ECM molecules showed aberrant localization in Bral1-deficient mice. Our results suggest that Bral1 plays an essential role of stabilizing extracellular matricies at the node of Ranvier and ECM complex is partially concerned with conduction velocity in the CNS. Research funds: KAKENHI (17046012, 18791206)
Research fund: KAKENHI 17790736
O1P-EØ3 High-threshold voltage-gated Ca2+ channels may mediate capacitive Ca2+ entry in central neurons Toshihide Tabata, Masanobu Kano Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan
O1P-EØ6 Balanced inputs “clamps” firing irregularity decoupled from rate fluctuations on any timescale Keiji Miura 1,2,3 , Yasuhiro Tsubo 3 , Tomoki Fukai 1,3 , Masato Okada 1,3 1 University of Tokyo, Chiba, Japan; 2 JSPS Research Fellow, Japan; 3 RIKEN, Japan
In central neurons, Ca2+ derived from the intracellular stores plays important roles such as induction of synaptic plasticity. The stores running out of Ca2+ are refilled with Ca2+ entering through cation channels on the plasma membrane. Using fura-2 fluorometry, we characterized Ca2+ influx following thapsigargin-induced depletion of the intracellular stores in cultured mouse cerebellar Purkinje cells. Agatoxin IVA (agaIVA), a P/Q-type high-threshold voltage-gated Ca2+ channel (hVGCC) blocker greatly reduced this Ca2+ influx. Store depletion might also activate cation channels whose auxiliary Na+ conductance could possibly cause depolarization and activation of hVGCCs. However, this cannot explain the agaIVA-sensitive Ca2+ influx because it persisted in Na+ -free saline. Moreover, the agaIVA-sensitive Ca2+ influx was susceptible to xestospongin C, an inositol trisphosphate receptor antagonist. These results suggest that P/Q-type hVGCCs may contribute to intracellular store refilling in central neurons.
Cortical neurons exhibit highly irregular spike patterns. Since interspike intervals fluctuate greatly, irregular firing makes it difficult to estimate instantaneous firing rates accurately. If, however, the spiking irregularity is decoupled from rate modulations, the estimate can be improved. Here, we introduce a novel coding scheme to make the firing irregularity orthogonal to the firing rate in information representation. The scheme is valid if an interspike interval distribution can be well fitted by the gamma distribution. We investigated in computational models and whole-cell patch-clamp recordings whether fluctuating current input generate gamma process-like spike outputs, and whether the two quantities are actually decoupled. The spiking irregularity remained approximately constant irrespective of large rate fluctuations when we injected balanced inputs where excitatory and inhibitory synapses are activated concurrently. These results indicate that the balanced input may improve coding efficiency by clamping spiking irregularity.
Research funds: KAKENHI 18019022, 17023021, and 17100004
Research fund: KAKENHI (18020007, 18079003, 1810171)
O1P-EØ4 Why does the neuronal firing rate increase with a
O1P-EØ7 Non-uniformity of membrane property improves den-
greater injected current?
dritic signal transfer in hippocampal CA1 pyramidal neuron
Katsumi Wada, Yutaka Sakaguchi Graduate School of Information Systems, University of Electro-Communidations, Tokyo, Japan
Toshiaki Omori 1,2 , Toru Aonishi 2,3 , Masato Okada 2,4 1 JSPS Research Fellow, Japan; 2 RIKEN Brain Science Institute, Japan; 3 Titech, Japan; 4 University of Tokyo, Japan
Neuronal firing rate increases as a greater current injected into the neuron. It is broadly believed that the speeded increase in membrane potential caused by a larger current shortens the time for exceeding the threshold level, and thus reduces the periods. However, this understanding is surprisingly ungrounded. The present study addresses the mechanism determining the relationship between the input current and firing rate using a simplified Hodgkin-Huxley model with two state variables, whose behavior can be readily analyzed on a phase plane. Our analysis revealed that the increase in the firing rate stemmed from the elevated level of interspike membrane potential and the reduction in the amplitude of oscillation of K+ conductance, and that the latter factor originated from the increase in the minimum level of K+ conductance activation. In other words, the reduction of the path length on the phase plane for each cycle of spike generation is the essential cause for shortening the period. This suggests a close relationship between the neuronal firing rate and the spike amplitude.
It is controversial whether somatic firing can be induced just with synaptic inputs to distal dendrite. Recent computational and experimental studies (Omori et al., 2006) revealed a spatial profile of dendritic membrane property in hippocampal CA1 pyramidal neurons; there is a steep decrease of membrane resistance between distal and proximal dendrites and distal dendrite is leakier than proximal one. To clarify effect of the non-uniformity on signal transfer from distal dendrite to soma, we analyzed cable equation and performed simulations of compartment model assuming non-uniform membrane property. Results by simulations show that anterograde signal transfer is enhanced due to the non-uniformity; somatic firing is induced by distal inputs in non-uniform model whereas no somatic firing is induced with the same inputs in uniform model. Our results suggest that non-uniform membrane property has functional role to improve dendritic signal transfer and to promote somatic firing just with inputs to distal dendrite. Research fund: KAKENHI (06J06774, 18020007, 18079003, 18700299)
Abstracts / Neuroscience Research 58S (2007) S1–S244
O1P-EØ2 Nav1.1 predominantly localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in Nav1.1-deficient mice I. Ogiwara 1 , H. Miyamoto 2 , N. Morita 3 , N. Atapour 2 , E. Mazaki 1 , I. Inoue 1 , Y. Yanagawa 5 , K. Obata 4 , T. Furuichi 3 , T.K. Hensch 2 , K. Yamakawa 1 1 Laboratory of Neurogenetics, RIKEN-BSI, Japan; 2 Laboratory of Neuronal Circuit Development, RIKEN-BSI, Japan; 3 Laboratory for Molecular Neurogenesis, RIKEN-BSI, Japan; 4 Neuronal Circuit Mechanisms Research Group, RIKEN-BSI, Japan; 5 Department of Genetics and Behavioural Neuroscience, Gunma University and SORST, JST, Japan We have recently generated a Nav1.1-deficient mouse line and shown that these mutant mice developed epileptic seizures. We here report Nav1.1 localization in the developing neocortex and hippocampus. In neocortex, Nav1.1 is predominantly found at the axon initial segments (AISs) of parvalbumin-positive (PV) interneurons. Moreover, in mutant mice, trains of evoked action potentials in these PV, fast-spiking cells exhibited pronounced spike amplitude decrement late in the burst. In the hippocampus, Nav1.1 is predominantly distributed within AISs and somata of PV interneurons. Our data indicate that Nav1.1 plays critical roles in the spike output from PV interneurons and further, that the specifically altered function of these inhibitory circuits may contribute to epileptic seizures in the mice.
O1P-EØ5 Bral1, brain-specific link protein, is essential for stabilizing extracellular matrix at the node of Ranvier in the CNS Yoko Bekku, Yoshifumi Ninomiya, Toshitaka Oohashi Department of Molecular Biology & Biochemistry, Okayama University, Okayama, Japan Myelinated axons in the nervous system are organized into distinct domains with glial cell. The node of Ranvier ensures rapid propagation of the action potential along myelinated fibers. The hyaluronan binding chondroitin sulfate proteoglycans, called lecticans are the abundant ECM molecules in the brain. Brain link protein-1 (Bral1) is colocalized with versican V2, a lectican member, at the node of Ranvier in the CNS. In this study, we have generated Bral1-deficient mice via homologous recombination in embryonic stem cell. The formation and structure of myelin appeared normal. However, conduction velocity of the optic nerves of mutant mice showed about 20% decrease as compared with that of controls. Moreover, versican V2 and other ECM molecules showed aberrant localization in Bral1-deficient mice. Our results suggest that Bral1 plays an essential role of stabilizing extracellular matricies at the node of Ranvier and ECM complex is partially concerned with conduction velocity in the CNS. Research funds: KAKENHI (17046012, 18791206)
Research fund: KAKENHI 17790736
O1P-EØ3 High-threshold voltage-gated Ca2+ channels may mediate capacitive Ca2+ entry in central neurons Toshihide Tabata, Masanobu Kano Department of Cellular Neuroscience, Graduate School of Medicine, Osaka University, Osaka, Japan
O1P-EØ6 Balanced inputs “clamps” firing irregularity decoupled from rate fluctuations on any timescale Keiji Miura 1,2,3 , Yasuhiro Tsubo 3 , Tomoki Fukai 1,3 , Masato Okada 1,3 1 University of Tokyo, Chiba, Japan; 2 JSPS Research Fellow, Japan; 3 RIKEN, Japan
In central neurons, Ca2+ derived from the intracellular stores plays important roles such as induction of synaptic plasticity. The stores running out of Ca2+ are refilled with Ca2+ entering through cation channels on the plasma membrane. Using fura-2 fluorometry, we characterized Ca2+ influx following thapsigargin-induced depletion of the intracellular stores in cultured mouse cerebellar Purkinje cells. Agatoxin IVA (agaIVA), a P/Q-type high-threshold voltage-gated Ca2+ channel (hVGCC) blocker greatly reduced this Ca2+ influx. Store depletion might also activate cation channels whose auxiliary Na+ conductance could possibly cause depolarization and activation of hVGCCs. However, this cannot explain the agaIVA-sensitive Ca2+ influx because it persisted in Na+ -free saline. Moreover, the agaIVA-sensitive Ca2+ influx was susceptible to xestospongin C, an inositol trisphosphate receptor antagonist. These results suggest that P/Q-type hVGCCs may contribute to intracellular store refilling in central neurons.
Cortical neurons exhibit highly irregular spike patterns. Since interspike intervals fluctuate greatly, irregular firing makes it difficult to estimate instantaneous firing rates accurately. If, however, the spiking irregularity is decoupled from rate modulations, the estimate can be improved. Here, we introduce a novel coding scheme to make the firing irregularity orthogonal to the firing rate in information representation. The scheme is valid if an interspike interval distribution can be well fitted by the gamma distribution. We investigated in computational models and whole-cell patch-clamp recordings whether fluctuating current input generate gamma process-like spike outputs, and whether the two quantities are actually decoupled. The spiking irregularity remained approximately constant irrespective of large rate fluctuations when we injected balanced inputs where excitatory and inhibitory synapses are activated concurrently. These results indicate that the balanced input may improve coding efficiency by clamping spiking irregularity.
Research funds: KAKENHI 18019022, 17023021, and 17100004
Research fund: KAKENHI (18020007, 18079003, 1810171)
O1P-EØ4 Why does the neuronal firing rate increase with a
O1P-EØ7 Non-uniformity of membrane property improves den-
greater injected current?
dritic signal transfer in hippocampal CA1 pyramidal neuron
Katsumi Wada, Yutaka Sakaguchi Graduate School of Information Systems, University of Electro-Communidations, Tokyo, Japan
Toshiaki Omori 1,2 , Toru Aonishi 2,3 , Masato Okada 2,4 1 JSPS Research Fellow, Japan; 2 RIKEN Brain Science Institute, Japan; 3 Titech, Japan; 4 University of Tokyo, Japan
Neuronal firing rate increases as a greater current injected into the neuron. It is broadly believed that the speeded increase in membrane potential caused by a larger current shortens the time for exceeding the threshold level, and thus reduces the periods. However, this understanding is surprisingly ungrounded. The present study addresses the mechanism determining the relationship between the input current and firing rate using a simplified Hodgkin-Huxley model with two state variables, whose behavior can be readily analyzed on a phase plane. Our analysis revealed that the increase in the firing rate stemmed from the elevated level of interspike membrane potential and the reduction in the amplitude of oscillation of K+ conductance, and that the latter factor originated from the increase in the minimum level of K+ conductance activation. In other words, the reduction of the path length on the phase plane for each cycle of spike generation is the essential cause for shortening the period. This suggests a close relationship between the neuronal firing rate and the spike amplitude.
It is controversial whether somatic firing can be induced just with synaptic inputs to distal dendrite. Recent computational and experimental studies (Omori et al., 2006) revealed a spatial profile of dendritic membrane property in hippocampal CA1 pyramidal neurons; there is a steep decrease of membrane resistance between distal and proximal dendrites and distal dendrite is leakier than proximal one. To clarify effect of the non-uniformity on signal transfer from distal dendrite to soma, we analyzed cable equation and performed simulations of compartment model assuming non-uniform membrane property. Results by simulations show that anterograde signal transfer is enhanced due to the non-uniformity; somatic firing is induced by distal inputs in non-uniform model whereas no somatic firing is induced with the same inputs in uniform model. Our results suggest that non-uniform membrane property has functional role to improve dendritic signal transfer and to promote somatic firing just with inputs to distal dendrite. Research fund: KAKENHI (06J06774, 18020007, 18079003, 18700299)