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A new view of synaptic integration in neocortical pyramidal neurons
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Abstracts / Neuroscience Research 68S (2010) e4–e52
are expressed by OSNs in a complementary and graded pattern in the OE. Although the soluble ligand, Sema3F, is not produced by the target cells in the OB, it is secreted by D-zone axons and deposited in the anterodorsal area of the OB. These results indicate a novel strategy for topographic map formation where early-arriving axons deliver the repulsive ligand to the target to act as a guidance cues to repel late-arriving, receptor-positive axons (Takeuchi et al., in press). Imai et al.: Science 325, 585-590 (2009) Takeuchi et al.: Cell (in press).
ble threshold spiking mechanism with NMDA spikes feeding into the apical calcium zone. In this presentation, I will discuss these requirements for activation of layer 5 pyramidal neurons and place them in the context of recent recordings of layer 5 pyramidal neuron tuft dendritic activity in vivo. doi:10.1016/j.neures.2010.07.286
S1-6-2-2 Dendritic dimensions and signal conduction properties of cortical nonpyramidal cells Yoshiyuki Kubota 1,2,3 , Fuyuki Karube 1,2 , Masaki Nomura 2,4 , Allan T Gulledge 5 , Atsushi Mochizuki 6 , Yasuo Kawaguchi 1,2,3 1
doi:10.1016/j.neures.2010.07.283
S1-6-1-3 Molecular mechanisms underlying the emergence of neural circuits Anirvan Ghosh Department of Neurobiology, University of California, San Diego We are investigating the molecular mechanisms that regulate the establishment of functional connections in the mammalian brain. We have found that neurons are able to identify and innervate their correct targets independent of patterning cues and activity, supporting a role for molecular recognition in target selection. We present evidence that Leucine Rich Repeat (LRR) proteins and cadherins and are likely mediators of synaptic specificity. Imaging experiments indicate that neurons make many transient synapses before stabilizing a small subset of potential connections. This decision is regulated by reverse signaling by an AMPA receptor-associated complex. These observations suggest that selective induction and stability contribute to the development of functional neural circuits. doi:10.1016/j.neures.2010.07.284
S1-6-1-4 Experience-dependent refinement of thalamocortical circuits Takao K. Hensch Molecular Cellular Biology, Harvard University Neural circuits are shaped by experience during periods of heightened brain plasticity in early postnatal life. In the developing visual cortex, specific inhibitory neurons initiate sensitivity to sensory deprivation, while molecular ‘brakes’ limit brain plasticity thereafter. Similarly in the auditory system, refinement of thalamocortical connectivity occurs within a brief, three-day window after hearing onset reflecting acoustic experience and GABA circuit activation. Voltage-sensitive dye imaging in an acute slice preparation reveals modification of thalamocortical response strength and topography that mirrors tonotopy following passive tone-rearing in vivo. Cortical remapping in the absence of thalamic reorganization is confirmed by accelerated spine maturation, critical period plasticity and functional development in mice lacking a forebrain-specific cell adhesion molecule. Taken together, the evolving postnatal connectivity between thalamus and cortex is tightly regulated by shared mechanisms across systems in the days following sensory input. doi:10.1016/j.neures.2010.07.285
S1-6-2-1 A new view of synaptic integration in neocortical pyramidal neurons Matthew E. Larkum Department of Physiology, University of Bern The discovery of NMDA spikes in the tuft dendrites of layer 5 neocortical pyramidal neurons raises questions about the rules for synaptic integration in these neurons. Using combined two-photon fluorescence microscopy with infrared-scanning gradient contrast we show that the most distal tuft dendrites of layer 5 pyramidal neurons from rat neocortex in vitro require relatively little (perhaps as few as 8) synaptic inputs for the generation of a local NMDA spike. Furthermore, while NMDA spikes are more easily recruited at locations near the terminals of the apical tuft dendrites, calcium spikes could not normally be generated in these branches. Our results suggest that synaptic input to these most distal tuft dendrites could not normally evoke calcium spikes even in the main apical shaft dendrite unless two or more NMDA spikes were evoked. From these findings a new view of synaptic integration in pyramidal neurons emerges. Many of the fibers in layer 1 of the cortex carry top-down information which is apparently subjected to a dou-
Division of Cerebral Circuitry, National Institute for Physiological Sciences JST, CREST, Tokyo, Japan 3 SOKENDAI, Okazaki, Japan 4 Department of Mathematics, Kyoto University, Kyoto, Japan 5 Department of Physiology and Neurobiology, Dartmouth Medical School, Lebanon NH, U.S.A 6 Theoretical Biology Laboratory, RIKEN Advanced Science Institute, Wako, Japan
2
Neurons receive thousands of synaptic inputs onto their dendrites and soma, and spatially and temporally integrate these inputs to produce appropriate output in the form of action potentials generated in axons. The morphology of dendrites can influence the integration of synaptic input, as well as effect the pattern of action potentials generated by suprathreshold stimuli. Using three-dimensional reconstructions from light and electron microscopic observations, we quantified the morphologies of the dendritic trees of four cortical interneuron subtypes present in the rat frontal cortex: Martinotti cells, fast spiking basket cells, double bouquet neurons, and large-basket neurons. Our ultrastructural data reveal four conserved principles governing the dendritic dimensions of these neurons. First, the cross-sectional area at any given point within a dendrite is proportional to the summed length of distally located dendrites beyond it, including all subsequent dendritic branches. Second, the total cross-sectional area is conserved at dendritic bifurcation points. Third, dendritic cross-sections are typically irregular ellipsoids rather than circles. Finally, in all neurons we found branch diameters consistent with Rall’s conductance matching assumption for dendritic bifurcations. These conserved features may facilitate even distribution of cellular components, as well as somatic depolarization, into all compartments of the dendritic tree, and may also limit the effects of dendritic topology on action potential generation. doi:10.1016/j.neures.2010.07.287
S1-6-2-3 Analysis of the impact of extracellular electric fields on hippocampal CA1 pyramidal neurons Hiroyoshi Miyakawa 1 , Masashi Inoue 1 , Toru Aonishi 2 1 Lab. Cellular Neurobiol., Sch. Life Sci., Tokyo University Pharm. and Life Sci., Tokyo, Japan 2 Department, Comp. Intel. Systems Sci., Tokyo Inst. Tech., Kanagawa, Japan
The importance of the dendrites in determining the outputs of neurons has been recognized for some time. We are interested in ephaptic interaction, a non-synaptic electrical interaction among neurons via extracellular electric fields, and have been studying the impact of extracellular electric fields on the membrane potential of hippocampal CA1 pyramidal neurons. By employing voltage-sensitive dye imaging technique, we have found that the membrane potential at the distal part of the apical dendrites show a peculiar response, a reversal in polarization during DC field stimulation and slow change in membrane potential at the soma. Performing compartmental simulations, we proposed that low resistivity at the distal dendrites can be one possible account for these behavior. In order to study further the behavior of dendritic membrane in electric fields, an oscillating field in particular, we obtained Green’s function of a passive finite cable with a shunt attached to one end for an impulse extracellular electric field. Analytic solutions for a DC electric field calculated by convolution of Green’s function showed the response reversal at the shunt-attached end and slow change at the opposite end, confirming compartment model simulations. Solutions for AC electric fields showed a frequency preference of the response amplitude at the shunt-attached end. This result implies that the membrane potential of CA1 pyramidal neuron might show frequency preference for AC field at the distal apical dendrites thoroughly due to passive properties of the membrane. We plan to test this possibility by making whole cell recordings from the distal apical dendrites exposed to oscillating extracellular electric fields. doi:10.1016/j.neures.2010.07.288
Abstracts / Neuroscience Research 68S (2010) e4–e52
are expressed by OSNs in a complementary and graded pattern in the OE. Although the soluble ligand, Sema3F, is not produced by the target cells in the OB, it is secreted by D-zone axons and deposited in the anterodorsal area of the OB. These results indicate a novel strategy for topographic map formation where early-arriving axons deliver the repulsive ligand to the target to act as a guidance cues to repel late-arriving, receptor-positive axons (Takeuchi et al., in press). Imai et al.: Science 325, 585-590 (2009) Takeuchi et al.: Cell (in press).
ble threshold spiking mechanism with NMDA spikes feeding into the apical calcium zone. In this presentation, I will discuss these requirements for activation of layer 5 pyramidal neurons and place them in the context of recent recordings of layer 5 pyramidal neuron tuft dendritic activity in vivo. doi:10.1016/j.neures.2010.07.286
S1-6-2-2 Dendritic dimensions and signal conduction properties of cortical nonpyramidal cells Yoshiyuki Kubota 1,2,3 , Fuyuki Karube 1,2 , Masaki Nomura 2,4 , Allan T Gulledge 5 , Atsushi Mochizuki 6 , Yasuo Kawaguchi 1,2,3 1
doi:10.1016/j.neures.2010.07.283
S1-6-1-3 Molecular mechanisms underlying the emergence of neural circuits Anirvan Ghosh Department of Neurobiology, University of California, San Diego We are investigating the molecular mechanisms that regulate the establishment of functional connections in the mammalian brain. We have found that neurons are able to identify and innervate their correct targets independent of patterning cues and activity, supporting a role for molecular recognition in target selection. We present evidence that Leucine Rich Repeat (LRR) proteins and cadherins and are likely mediators of synaptic specificity. Imaging experiments indicate that neurons make many transient synapses before stabilizing a small subset of potential connections. This decision is regulated by reverse signaling by an AMPA receptor-associated complex. These observations suggest that selective induction and stability contribute to the development of functional neural circuits. doi:10.1016/j.neures.2010.07.284
S1-6-1-4 Experience-dependent refinement of thalamocortical circuits Takao K. Hensch Molecular Cellular Biology, Harvard University Neural circuits are shaped by experience during periods of heightened brain plasticity in early postnatal life. In the developing visual cortex, specific inhibitory neurons initiate sensitivity to sensory deprivation, while molecular ‘brakes’ limit brain plasticity thereafter. Similarly in the auditory system, refinement of thalamocortical connectivity occurs within a brief, three-day window after hearing onset reflecting acoustic experience and GABA circuit activation. Voltage-sensitive dye imaging in an acute slice preparation reveals modification of thalamocortical response strength and topography that mirrors tonotopy following passive tone-rearing in vivo. Cortical remapping in the absence of thalamic reorganization is confirmed by accelerated spine maturation, critical period plasticity and functional development in mice lacking a forebrain-specific cell adhesion molecule. Taken together, the evolving postnatal connectivity between thalamus and cortex is tightly regulated by shared mechanisms across systems in the days following sensory input. doi:10.1016/j.neures.2010.07.285
S1-6-2-1 A new view of synaptic integration in neocortical pyramidal neurons Matthew E. Larkum Department of Physiology, University of Bern The discovery of NMDA spikes in the tuft dendrites of layer 5 neocortical pyramidal neurons raises questions about the rules for synaptic integration in these neurons. Using combined two-photon fluorescence microscopy with infrared-scanning gradient contrast we show that the most distal tuft dendrites of layer 5 pyramidal neurons from rat neocortex in vitro require relatively little (perhaps as few as 8) synaptic inputs for the generation of a local NMDA spike. Furthermore, while NMDA spikes are more easily recruited at locations near the terminals of the apical tuft dendrites, calcium spikes could not normally be generated in these branches. Our results suggest that synaptic input to these most distal tuft dendrites could not normally evoke calcium spikes even in the main apical shaft dendrite unless two or more NMDA spikes were evoked. From these findings a new view of synaptic integration in pyramidal neurons emerges. Many of the fibers in layer 1 of the cortex carry top-down information which is apparently subjected to a dou-
Division of Cerebral Circuitry, National Institute for Physiological Sciences JST, CREST, Tokyo, Japan 3 SOKENDAI, Okazaki, Japan 4 Department of Mathematics, Kyoto University, Kyoto, Japan 5 Department of Physiology and Neurobiology, Dartmouth Medical School, Lebanon NH, U.S.A 6 Theoretical Biology Laboratory, RIKEN Advanced Science Institute, Wako, Japan
2
Neurons receive thousands of synaptic inputs onto their dendrites and soma, and spatially and temporally integrate these inputs to produce appropriate output in the form of action potentials generated in axons. The morphology of dendrites can influence the integration of synaptic input, as well as effect the pattern of action potentials generated by suprathreshold stimuli. Using three-dimensional reconstructions from light and electron microscopic observations, we quantified the morphologies of the dendritic trees of four cortical interneuron subtypes present in the rat frontal cortex: Martinotti cells, fast spiking basket cells, double bouquet neurons, and large-basket neurons. Our ultrastructural data reveal four conserved principles governing the dendritic dimensions of these neurons. First, the cross-sectional area at any given point within a dendrite is proportional to the summed length of distally located dendrites beyond it, including all subsequent dendritic branches. Second, the total cross-sectional area is conserved at dendritic bifurcation points. Third, dendritic cross-sections are typically irregular ellipsoids rather than circles. Finally, in all neurons we found branch diameters consistent with Rall’s conductance matching assumption for dendritic bifurcations. These conserved features may facilitate even distribution of cellular components, as well as somatic depolarization, into all compartments of the dendritic tree, and may also limit the effects of dendritic topology on action potential generation. doi:10.1016/j.neures.2010.07.287
S1-6-2-3 Analysis of the impact of extracellular electric fields on hippocampal CA1 pyramidal neurons Hiroyoshi Miyakawa 1 , Masashi Inoue 1 , Toru Aonishi 2 1 Lab. Cellular Neurobiol., Sch. Life Sci., Tokyo University Pharm. and Life Sci., Tokyo, Japan 2 Department, Comp. Intel. Systems Sci., Tokyo Inst. Tech., Kanagawa, Japan
The importance of the dendrites in determining the outputs of neurons has been recognized for some time. We are interested in ephaptic interaction, a non-synaptic electrical interaction among neurons via extracellular electric fields, and have been studying the impact of extracellular electric fields on the membrane potential of hippocampal CA1 pyramidal neurons. By employing voltage-sensitive dye imaging technique, we have found that the membrane potential at the distal part of the apical dendrites show a peculiar response, a reversal in polarization during DC field stimulation and slow change in membrane potential at the soma. Performing compartmental simulations, we proposed that low resistivity at the distal dendrites can be one possible account for these behavior. In order to study further the behavior of dendritic membrane in electric fields, an oscillating field in particular, we obtained Green’s function of a passive finite cable with a shunt attached to one end for an impulse extracellular electric field. Analytic solutions for a DC electric field calculated by convolution of Green’s function showed the response reversal at the shunt-attached end and slow change at the opposite end, confirming compartment model simulations. Solutions for AC electric fields showed a frequency preference of the response amplitude at the shunt-attached end. This result implies that the membrane potential of CA1 pyramidal neuron might show frequency preference for AC field at the distal apical dendrites thoroughly due to passive properties of the membrane. We plan to test this possibility by making whole cell recordings from the distal apical dendrites exposed to oscillating extracellular electric fields. doi:10.1016/j.neures.2010.07.288