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Mark F Yeckel - One of the best experts on this subject based on the ideXlab platform.
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metabotropic glutamate receptors regulate hippocampal ca1 Pyramidal Neuron excitability via ca2 wave dependent activation of sk and trpc channels
The Journal of Physiology, 2011Co-Authors: Lynda Elhassar, Anna M Hagenston, Lisa Bertetto Dangelo, Mark F YeckelAbstract:Non-technical summary The hippocampus is a neural structure that is critical for some forms of memory function. It performs this function through the ability of its Neurons to fire patterns of activity that encode information and the ability of the synaptic connections between Neurons to strengthen or weaken. Glutamate, an important synaptic neurotransmitter, can activate different types of receptors, including metabotropic glutamate receptors (mGluRs). mGluRs have been shown to be important for learning and memory. It has also been shown that changes in mGluR type 5 might contribute to mental retardation and autism, suggesting that manipulation of mGluR5 might reduce their symptoms. In this study we examined how mGluR activation can activate Neuron membrane channels (SK and TRPC) in hippocampal Neurons that regulate their activity. Our findings suggest that mGluR activation of SK and TRPC channels are likely to be important for sculpting patterns of activity that encode information by the hippocampus. Abstract Group I metabotropic glutamate receptors (mGluRs) play an essential role in cognitive function. Their activation results in a wide array of cellular and molecular responses that are mediated by multiple signalling cascades. In this study, we focused on Group I mGluR activation of IP3R-mediated intracellular Ca2+ waves and their role in activating Ca2+-dependent ion channels in CA1 Pyramidal Neurons. Using whole-cell patch-clamp recordings and high-speed Ca2+ fluorescence imaging in acute hippocampal brain slices, we show that synaptic and pharmacological stimulation of mGluRs triggers intracellular Ca2+ waves and a biphasic electrical response composed of a transient Ca2+-dependent SK channel-mediated hyperpolarization and a TRPC-mediated sustained depolarization. The generation and magnitude of the SK channel-mediated hyperpolarization depended solely on the rise in intracellular Ca2+ concentration ([Ca2+]i), whereas the TRPC channel-mediated depolarization required both a small rise in [Ca2+]i and mGluR activation. Furthermore, the TRPC-mediated current was suppressed by forskolin-induced rises in cAMP. We also show that SK- and TRPC-mediated currents robustly modulate Pyramidal Neuron excitability by decreasing and increasing their firing frequency, respectively. These findings provide additional evidence that mGluR-mediated synaptic transmission makes an important contribution to regulating the output of hippocampal Neurons through intracellular Ca2+ wave activation of SK and TRPC channels. cAMP provides an additional level of regulation by modulating TRPC-mediated sustained depolarization that we propose to be important for stabilizing periods of sustained firing.
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metabotropic glutamate receptors regulate hippocampal ca1 Pyramidal Neuron excitability via ca2 wave dependent activation of sk and trpc channels
The Journal of Physiology, 2011Co-Authors: Lynda Elhassar, Anna M Hagenston, Lisa Bertetto Dangelo, Mark F YeckelAbstract:Group I metabotropic glutamate receptors (mGluRs) play an essential role in cognitive function. Their activation results in a wide array of cellular and molecular responses that are mediated by multiple signalling cascades. In this study, we focused on Group I mGluR activation of IP3R-mediated intracellular Ca2+ waves and their role in activating Ca2+-dependent ion channels in CA1 Pyramidal Neurons. Using whole-cell patch-clamp recordings and high-speed Ca2+ fluorescence imaging in acute hippocampal brain slices, we show that synaptic and pharmacological stimulation of mGluRs triggers intracellular Ca2+ waves and a biphasic electrical response composed of a transient Ca2+-dependent SK channel-mediated hyperpolarization and a TRPC-mediated sustained depolarization. The generation and magnitude of the SK channel-mediated hyperpolarization depended solely on the rise in intracellular Ca2+ concentration ([Ca2+]i), whereas the TRPC channel-mediated depolarization required both a small rise in [Ca2+]i and mGluR activation. Furthermore, the TRPC-mediated current was suppressed by forskolin-induced rises in cAMP. We also show that SK- and TRPC-mediated currents robustly modulate Pyramidal Neuron excitability by decreasing and increasing their firing frequency, respectively. These findings provide additional evidence that mGluR-mediated synaptic transmission makes an important contribution to regulating the output of hippocampal Neurons through intracellular Ca2+ wave activation of SK and TRPC channels. cAMP provides an additional level of regulation by modulating TRPC-mediated sustained depolarization that we propose to be important for stabilizing periods of sustained firing.
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inositol 1 4 5 trisphosphate receptor mediated ca2 waves in Pyramidal Neuron dendrites propagate through hot spots and cold spots
The Journal of Physiology, 2009Co-Authors: John S Fitzpatrick, Anna M Hagenston, Daniel N Hertle, Keith E Gipson, Lisa Bertettodangelo, Mark F YeckelAbstract:We studied inositol-1,4,5-trisphosphate (IP3) receptor-dependent intracellular Ca2+ waves in CA1 hippocampal and layer V medial prefrontal cortical Pyramidal Neurons using whole-cell patch-clamp recordings and Ca2+ fluorescence imaging. We observed that Ca2+ waves propagate in a saltatory manner through dendritic regions where increases in the intracellular concentration of Ca2+ ([Ca2+]i) were large and fast (‘hot spots’) separated by regions where increases in [Ca2+]i were comparatively small and slow (‘cold spots’). We also observed that Ca2+ waves typically initiate in hot spots and terminate in cold spots, and that most hot spots, but few cold spots, are located at dendritic branch points. Using immunohistochemistry, we found that IP3 receptors (IP3Rs) are distributed in clusters along Pyramidal Neuron dendrites and that the distribution of inter-cluster distances is nearly identical to the distribution of inter-hot spot distances. These findings support the hypothesis that the dendritic locations of Ca2+ wave hot spots in general, and branch points in particular, are specially equipped for regenerative IP3R-dependent internal Ca2+ release. Functionally, the observation that IP3R-dependent [Ca2+]i rises are greater at branch points raises the possibility that this novel Ca2+ signal may be important for the regulation of Ca2+-dependent processes in these locations. Futhermore, the observation that Ca2+ waves tend to fail between hot spots raises the possibility that influences on Ca2+ wave propagation may determine the degree of functional association between distinct Ca2+-sensitive dendritic domains.
Nelson Spruston - One of the best experts on this subject based on the ideXlab platform.
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factors mediating powerful voltage attenuation along ca1 Pyramidal Neuron dendrites
The Journal of Physiology, 2005Co-Authors: Timothy Mickus, Nace L Golding, Yael Katz, William L Kath, Nelson SprustonAbstract:We performed simultaneous patch-electrode recordings from the soma and apical dendrite of CA1 Pyramidal Neurons in hippocampal slices, in order to determine the degree of voltage attenuation along CA1 dendrites. Fifty per cent attenuation of steady-state somatic voltage changes occurred at a distance of 238 μm from the soma in control and 409 μm after blocking the hyperpolarization-activated (H) conductance. The morphology of three Neurons was reconstructed and used to generate computer models, which were adjusted to fit the somatic and dendritic voltage responses. These models identify several factors contributing to the voltage attenuation along CA1 dendrites, including high axial cytoplasmic resistivity, low membrane resistivity, and large H conductance. In most cells the resting membrane conductances, including the H conductances, were larger in the dendrites than the soma. Simulations suggest that synaptic potentials attenuate enormously as they propagate from the dendrite to the soma, with greater than 100-fold attenuation for synapses on many small, distal dendrites. A prediction of this powerful EPSP attenuation is that distal synaptic inputs are likely only to be effective in the presence of conductance scaling, dendritic excitability, or both.
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dichotomy of action potential backpropagation in ca1 Pyramidal Neuron dendrites
Journal of Neurophysiology, 2001Co-Authors: Nace L Golding, William L Kath, Nelson SprustonAbstract:In hippocampal CA1 Pyramidal Neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the in...
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determinants of voltage attenuation in neocortical Pyramidal Neuron dendrites
The Journal of Neuroscience, 1998Co-Authors: Greg J Stuart, Nelson SprustonAbstract:How effectively synaptic and regenerative potentials propagate within Neurons depends critically on the membrane properties and intracellular resistivity of the dendritic tree. These properties therefore are important determinants of Neuronal function. Here we use simultaneous whole-cell patch-pipette recordings from the soma and apical dendrite of neocortical layer 5 Pyramidal Neurons to directly measure voltage attenuation in cortical Neurons. When combined with morphologically realistic compartmental models of the same cells, the data suggest that the intracellular resistivity of neocortical Pyramidal Neurons is relatively low ( approximately 70 to 100 Omegacm), but that voltage attenuation is substantial because of nonuniformly distributed resting conductances present at a higher density in the distal apical dendrites. These conductances, which were largely blocked by bath application of CsCl (5 mM), significantly increased steady-state voltage attenuation and decreased EPSP integral and peak in a manner that depended on the location of the synapse. Together these findings suggest that nonuniformly distributed Cs-sensitive and -insensitive resting conductances generate a "leaky" apical dendrite, which differentially influences the integration of spatially segregated synaptic inputs.
Nace L Golding - One of the best experts on this subject based on the ideXlab platform.
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factors mediating powerful voltage attenuation along ca1 Pyramidal Neuron dendrites
The Journal of Physiology, 2005Co-Authors: Timothy Mickus, Nace L Golding, Yael Katz, William L Kath, Nelson SprustonAbstract:We performed simultaneous patch-electrode recordings from the soma and apical dendrite of CA1 Pyramidal Neurons in hippocampal slices, in order to determine the degree of voltage attenuation along CA1 dendrites. Fifty per cent attenuation of steady-state somatic voltage changes occurred at a distance of 238 μm from the soma in control and 409 μm after blocking the hyperpolarization-activated (H) conductance. The morphology of three Neurons was reconstructed and used to generate computer models, which were adjusted to fit the somatic and dendritic voltage responses. These models identify several factors contributing to the voltage attenuation along CA1 dendrites, including high axial cytoplasmic resistivity, low membrane resistivity, and large H conductance. In most cells the resting membrane conductances, including the H conductances, were larger in the dendrites than the soma. Simulations suggest that synaptic potentials attenuate enormously as they propagate from the dendrite to the soma, with greater than 100-fold attenuation for synapses on many small, distal dendrites. A prediction of this powerful EPSP attenuation is that distal synaptic inputs are likely only to be effective in the presence of conductance scaling, dendritic excitability, or both.
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dichotomy of action potential backpropagation in ca1 Pyramidal Neuron dendrites
Journal of Neurophysiology, 2001Co-Authors: Nace L Golding, William L Kath, Nelson SprustonAbstract:In hippocampal CA1 Pyramidal Neurons, action potentials are typically initiated in the axon and backpropagate into the dendrites, shaping the integration of synaptic activity and influencing the in...
Anna M Hagenston - One of the best experts on this subject based on the ideXlab platform.
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metabotropic glutamate receptors regulate hippocampal ca1 Pyramidal Neuron excitability via ca2 wave dependent activation of sk and trpc channels
The Journal of Physiology, 2011Co-Authors: Lynda Elhassar, Anna M Hagenston, Lisa Bertetto Dangelo, Mark F YeckelAbstract:Non-technical summary The hippocampus is a neural structure that is critical for some forms of memory function. It performs this function through the ability of its Neurons to fire patterns of activity that encode information and the ability of the synaptic connections between Neurons to strengthen or weaken. Glutamate, an important synaptic neurotransmitter, can activate different types of receptors, including metabotropic glutamate receptors (mGluRs). mGluRs have been shown to be important for learning and memory. It has also been shown that changes in mGluR type 5 might contribute to mental retardation and autism, suggesting that manipulation of mGluR5 might reduce their symptoms. In this study we examined how mGluR activation can activate Neuron membrane channels (SK and TRPC) in hippocampal Neurons that regulate their activity. Our findings suggest that mGluR activation of SK and TRPC channels are likely to be important for sculpting patterns of activity that encode information by the hippocampus. Abstract Group I metabotropic glutamate receptors (mGluRs) play an essential role in cognitive function. Their activation results in a wide array of cellular and molecular responses that are mediated by multiple signalling cascades. In this study, we focused on Group I mGluR activation of IP3R-mediated intracellular Ca2+ waves and their role in activating Ca2+-dependent ion channels in CA1 Pyramidal Neurons. Using whole-cell patch-clamp recordings and high-speed Ca2+ fluorescence imaging in acute hippocampal brain slices, we show that synaptic and pharmacological stimulation of mGluRs triggers intracellular Ca2+ waves and a biphasic electrical response composed of a transient Ca2+-dependent SK channel-mediated hyperpolarization and a TRPC-mediated sustained depolarization. The generation and magnitude of the SK channel-mediated hyperpolarization depended solely on the rise in intracellular Ca2+ concentration ([Ca2+]i), whereas the TRPC channel-mediated depolarization required both a small rise in [Ca2+]i and mGluR activation. Furthermore, the TRPC-mediated current was suppressed by forskolin-induced rises in cAMP. We also show that SK- and TRPC-mediated currents robustly modulate Pyramidal Neuron excitability by decreasing and increasing their firing frequency, respectively. These findings provide additional evidence that mGluR-mediated synaptic transmission makes an important contribution to regulating the output of hippocampal Neurons through intracellular Ca2+ wave activation of SK and TRPC channels. cAMP provides an additional level of regulation by modulating TRPC-mediated sustained depolarization that we propose to be important for stabilizing periods of sustained firing.
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metabotropic glutamate receptors regulate hippocampal ca1 Pyramidal Neuron excitability via ca2 wave dependent activation of sk and trpc channels
The Journal of Physiology, 2011Co-Authors: Lynda Elhassar, Anna M Hagenston, Lisa Bertetto Dangelo, Mark F YeckelAbstract:Group I metabotropic glutamate receptors (mGluRs) play an essential role in cognitive function. Their activation results in a wide array of cellular and molecular responses that are mediated by multiple signalling cascades. In this study, we focused on Group I mGluR activation of IP3R-mediated intracellular Ca2+ waves and their role in activating Ca2+-dependent ion channels in CA1 Pyramidal Neurons. Using whole-cell patch-clamp recordings and high-speed Ca2+ fluorescence imaging in acute hippocampal brain slices, we show that synaptic and pharmacological stimulation of mGluRs triggers intracellular Ca2+ waves and a biphasic electrical response composed of a transient Ca2+-dependent SK channel-mediated hyperpolarization and a TRPC-mediated sustained depolarization. The generation and magnitude of the SK channel-mediated hyperpolarization depended solely on the rise in intracellular Ca2+ concentration ([Ca2+]i), whereas the TRPC channel-mediated depolarization required both a small rise in [Ca2+]i and mGluR activation. Furthermore, the TRPC-mediated current was suppressed by forskolin-induced rises in cAMP. We also show that SK- and TRPC-mediated currents robustly modulate Pyramidal Neuron excitability by decreasing and increasing their firing frequency, respectively. These findings provide additional evidence that mGluR-mediated synaptic transmission makes an important contribution to regulating the output of hippocampal Neurons through intracellular Ca2+ wave activation of SK and TRPC channels. cAMP provides an additional level of regulation by modulating TRPC-mediated sustained depolarization that we propose to be important for stabilizing periods of sustained firing.
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inositol 1 4 5 trisphosphate receptor mediated ca2 waves in Pyramidal Neuron dendrites propagate through hot spots and cold spots
The Journal of Physiology, 2009Co-Authors: John S Fitzpatrick, Anna M Hagenston, Daniel N Hertle, Keith E Gipson, Lisa Bertettodangelo, Mark F YeckelAbstract:We studied inositol-1,4,5-trisphosphate (IP3) receptor-dependent intracellular Ca2+ waves in CA1 hippocampal and layer V medial prefrontal cortical Pyramidal Neurons using whole-cell patch-clamp recordings and Ca2+ fluorescence imaging. We observed that Ca2+ waves propagate in a saltatory manner through dendritic regions where increases in the intracellular concentration of Ca2+ ([Ca2+]i) were large and fast (‘hot spots’) separated by regions where increases in [Ca2+]i were comparatively small and slow (‘cold spots’). We also observed that Ca2+ waves typically initiate in hot spots and terminate in cold spots, and that most hot spots, but few cold spots, are located at dendritic branch points. Using immunohistochemistry, we found that IP3 receptors (IP3Rs) are distributed in clusters along Pyramidal Neuron dendrites and that the distribution of inter-cluster distances is nearly identical to the distribution of inter-hot spot distances. These findings support the hypothesis that the dendritic locations of Ca2+ wave hot spots in general, and branch points in particular, are specially equipped for regenerative IP3R-dependent internal Ca2+ release. Functionally, the observation that IP3R-dependent [Ca2+]i rises are greater at branch points raises the possibility that this novel Ca2+ signal may be important for the regulation of Ca2+-dependent processes in these locations. Futhermore, the observation that Ca2+ waves tend to fail between hot spots raises the possibility that influences on Ca2+ wave propagation may determine the degree of functional association between distinct Ca2+-sensitive dendritic domains.
Lynda Elhassar - One of the best experts on this subject based on the ideXlab platform.
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metabotropic glutamate receptors regulate hippocampal ca1 Pyramidal Neuron excitability via ca2 wave dependent activation of sk and trpc channels
The Journal of Physiology, 2011Co-Authors: Lynda Elhassar, Anna M Hagenston, Lisa Bertetto Dangelo, Mark F YeckelAbstract:Non-technical summary The hippocampus is a neural structure that is critical for some forms of memory function. It performs this function through the ability of its Neurons to fire patterns of activity that encode information and the ability of the synaptic connections between Neurons to strengthen or weaken. Glutamate, an important synaptic neurotransmitter, can activate different types of receptors, including metabotropic glutamate receptors (mGluRs). mGluRs have been shown to be important for learning and memory. It has also been shown that changes in mGluR type 5 might contribute to mental retardation and autism, suggesting that manipulation of mGluR5 might reduce their symptoms. In this study we examined how mGluR activation can activate Neuron membrane channels (SK and TRPC) in hippocampal Neurons that regulate their activity. Our findings suggest that mGluR activation of SK and TRPC channels are likely to be important for sculpting patterns of activity that encode information by the hippocampus. Abstract Group I metabotropic glutamate receptors (mGluRs) play an essential role in cognitive function. Their activation results in a wide array of cellular and molecular responses that are mediated by multiple signalling cascades. In this study, we focused on Group I mGluR activation of IP3R-mediated intracellular Ca2+ waves and their role in activating Ca2+-dependent ion channels in CA1 Pyramidal Neurons. Using whole-cell patch-clamp recordings and high-speed Ca2+ fluorescence imaging in acute hippocampal brain slices, we show that synaptic and pharmacological stimulation of mGluRs triggers intracellular Ca2+ waves and a biphasic electrical response composed of a transient Ca2+-dependent SK channel-mediated hyperpolarization and a TRPC-mediated sustained depolarization. The generation and magnitude of the SK channel-mediated hyperpolarization depended solely on the rise in intracellular Ca2+ concentration ([Ca2+]i), whereas the TRPC channel-mediated depolarization required both a small rise in [Ca2+]i and mGluR activation. Furthermore, the TRPC-mediated current was suppressed by forskolin-induced rises in cAMP. We also show that SK- and TRPC-mediated currents robustly modulate Pyramidal Neuron excitability by decreasing and increasing their firing frequency, respectively. These findings provide additional evidence that mGluR-mediated synaptic transmission makes an important contribution to regulating the output of hippocampal Neurons through intracellular Ca2+ wave activation of SK and TRPC channels. cAMP provides an additional level of regulation by modulating TRPC-mediated sustained depolarization that we propose to be important for stabilizing periods of sustained firing.
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metabotropic glutamate receptors regulate hippocampal ca1 Pyramidal Neuron excitability via ca2 wave dependent activation of sk and trpc channels
The Journal of Physiology, 2011Co-Authors: Lynda Elhassar, Anna M Hagenston, Lisa Bertetto Dangelo, Mark F YeckelAbstract:Group I metabotropic glutamate receptors (mGluRs) play an essential role in cognitive function. Their activation results in a wide array of cellular and molecular responses that are mediated by multiple signalling cascades. In this study, we focused on Group I mGluR activation of IP3R-mediated intracellular Ca2+ waves and their role in activating Ca2+-dependent ion channels in CA1 Pyramidal Neurons. Using whole-cell patch-clamp recordings and high-speed Ca2+ fluorescence imaging in acute hippocampal brain slices, we show that synaptic and pharmacological stimulation of mGluRs triggers intracellular Ca2+ waves and a biphasic electrical response composed of a transient Ca2+-dependent SK channel-mediated hyperpolarization and a TRPC-mediated sustained depolarization. The generation and magnitude of the SK channel-mediated hyperpolarization depended solely on the rise in intracellular Ca2+ concentration ([Ca2+]i), whereas the TRPC channel-mediated depolarization required both a small rise in [Ca2+]i and mGluR activation. Furthermore, the TRPC-mediated current was suppressed by forskolin-induced rises in cAMP. We also show that SK- and TRPC-mediated currents robustly modulate Pyramidal Neuron excitability by decreasing and increasing their firing frequency, respectively. These findings provide additional evidence that mGluR-mediated synaptic transmission makes an important contribution to regulating the output of hippocampal Neurons through intracellular Ca2+ wave activation of SK and TRPC channels. cAMP provides an additional level of regulation by modulating TRPC-mediated sustained depolarization that we propose to be important for stabilizing periods of sustained firing.
