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Bert Sakmann - One of the best experts on this subject based on the ideXlab platform.
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synaptic conductance estimates of the connection between local inhibitor interneurons and pyramidal neurons in layer 2 3 of a Cortical Column
Cerebral Cortex, 2015Co-Authors: Bert Sakmann, Jochen H O Hoffmann, Hanno S Meyer, Arno C Schmitt, Jakob Straehle, Trinh Weitbrecht, Moritz HelmstaedterAbstract:Stimulation of a principal whisker yields sparse action potential (AP) spiking in layer 2/3 (L2/3) pyramidal neurons in a Cortical Column of rat barrel cortex. The low AP rates in pyramidal neurons could be explained by activation of interneurons in L2/3 providing inhibition onto L2/3 pyramidal neurons. L2/3 interneurons classified as local inhibitors based on their axonal projection in the same Column were reported to receive strong excitatory input from spiny neurons in L4, which are also the main source of the excitatory input to L2/3 pyramidal neurons. Here, we investigated the remaining synaptic connection in this intraColumnar microcircuit. We found strong and reliable inhibitory synaptic transmission between intraColumnar L2/3 local-inhibitor-to-L2/3 pyramidal neuron pairs [inhibitory postsynaptic potential (IPSP) amplitude -0.88 ± 0.67 mV]. On average, 6.2 ± 2 synaptic contacts were made by L2/3 local inhibitors onto L2/3 pyramidal neurons at 107 ± 64 µm path distance from the pyramidal neuron soma, thus overlapping with the distribution of synaptic contacts from L4 spiny neurons onto L2/3 pyramidal neurons (67 ± 34 µm). Finally, using compartmental simulations, we determined the synaptic conductance per synaptic contact to be 0.77 ± 0.4 nS. We conclude that the synaptic circuit from L4 to L2/3 can provide efficient shunting inhibition that is temporally and spatially aligned with the excitatory input from L4 to L2/3.
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cell type specific three dimensional structure of thalamoCortical circuits in a Column of rat vibrissal cortex
Cerebral Cortex, 2012Co-Authors: Marcel Oberlaender, Randy M. Bruno, Christiaan P. J. De Kock, Moritz Helmstaedter, Hanno S Meyer, Alejandro Ramirez, Vincent J Dercksen, Bert SakmannAbstract:Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory-evoked spiking. Here, we reconstruct the 3D circuits formed by thalamoCortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined Cortical Column in rat vibrissal cortex. We objectively classify 9 Cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamoCortical synapses. Somata and dendrites of most cell types intermingle, while thalamoCortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamoCortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location-specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type-specific lemniscal synaptic wiring diagram and elucidates structure-function relationships of this physiologically relevant pathway at single-cell resolution.
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Inhibitory interneurons in a Cortical Column form hot zones of inhibition in layers 2 and 5A
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Hanno S Meyer, Bert Sakmann, Verena C. Wimmer, Arno C Schmitt, Daniel Schwarz, Jason N D Kerr, Moritz HelmstaedterAbstract:Although physiological data on microcircuits involving a few inhibitory neurons in the mammalian cerebral cortex are available, data on the quantitative relation between inhibition and excitation in Cortical circuits involving thousands of neurons are largely missing. Because the distribution of neurons is very inhomogeneous in the cerebral cortex, it is critical to map all neurons in a given volume rather than to rely on sparse sampling methods. Here, we report the comprehensive mapping of interneurons (INs) in Cortical Columns of rat somatosensory cortex, immunolabeled for neuron-specific nuclear protein and glutamate decarboxylase. We found that a Column contains ∼2,200 INs (11.5% of ∼19,000 neurons), almost a factor of 2 less than previously estimated. The density of GABAergic neurons was inhomogeneous between layers, with peaks in the upper third of L2/3 and in L5A. IN density therefore defines a distinct layer 2 in the sensory neocortex. In addition, immunohistochemical markers of IN subtypes were layer-specific. The “hot zones” of inhibition in L2 and L5A match the reported low stimulus-evoked spiking rates of excitatory neurons in these layers, suggesting that these inhibitory hot zones substantially suppress activity in the neocortex.
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cell type specific thalamic innervation in a Column of rat vibrissal cortex
Cerebral Cortex, 2010Co-Authors: H S Meyer, Bert Sakmann, Verena C. Wimmer, Randy M. Bruno, Christiaan P. J. De Kock, Mike Hemberger, Andreas Frick, Moritz HelmstaedterAbstract:This is the concluding article in a series of 3 studies that investigate the anatomical determinants of thalamoCortical (TC) input to excitatory neurons in a Cortical Column of rat primary somatosensory cortex (S1). We used viral synaptophysin-enhanced green fluorescent protein expression in thalamic neurons and reconstructions of biocytin-labeled Cortical neurons in TC slices to quantify the number and distribution of boutons from the ventral posterior medial (VPM) and posteromedial (POm) nuclei potentially innervating dendritic arbors of excitatory neurons located in layers (L)2-6 of a Cortical Column in rat somatosensory cortex. We found that 1) all types of excitatory neurons potentially receive substantial TC input (90-580 boutons per neuron); 2) pyramidal neurons in L3-L6 receive dual TC input from both VPM and POm that is potentially of equal magnitude for thick-tufted L5 pyramidal neurons (ca. 300 boutons each from VPM and POm); 3) L3, L4, and L5 pyramidal neurons have multiple (2-4) subcellular TC innervation domains that match the dendritic compartments of pyramidal cells; and 4) a subtype of thick-tufted L5 pyramidal neurons has an additional VPM innervation domain in L4. The multiple subcellular TC innervation domains of L5 pyramidal neurons may partly explain their specific action potential patterns observed in vivo. We conclude that the substantial potential TC innervation of all excitatory neuron types in a Cortical Column constitutes an anatomical basis for the initial near-simultaneous representation of a sensory stimulus in different neuron types.
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Dimensions of a projection Column and architecture of VPM and POm axons in rat vibrissal cortex.
Cerebral Cortex, 2010Co-Authors: Verena C. Wimmer, Randy M. Bruno, Christiaan P. J. De Kock, Thomas Kuner, Bert SakmannAbstract:This is the first article in a series of 3 studies that investigate the anatomical determinants of thalamoCortical (TC) input to excitatory neurons in a Cortical Column of rat primary somatosensory cortex (S1). S1 receives 2 major types of TC inputs, lemiscal and paralemniscal. Lemiscal axons arise from the ventral posteromedial nucleus (VPM) of the thalamus, whereas paralemniscal fibers originate in the posteromedial nucleus (POm). While these 2 TC projections are largely complementary in L4, overlap in other Cortical layers is still a matter of debate. VPM and POm axons were specifically labeled in the same rat by virus-mediated expression of different fluorescent proteins. We show that Columnar and septal projection patterns are maintained throughout most of the Cortical depth with a lower degree of separation in infragranular layers, where TC axons form bands along rows. Finally, we present anatomical dimensions of "TC projection domains" for a standard Column in S1.
Moritz Helmstaedter - One of the best experts on this subject based on the ideXlab platform.
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synaptic conductance estimates of the connection between local inhibitor interneurons and pyramidal neurons in layer 2 3 of a Cortical Column
Cerebral Cortex, 2015Co-Authors: Bert Sakmann, Jochen H O Hoffmann, Hanno S Meyer, Arno C Schmitt, Jakob Straehle, Trinh Weitbrecht, Moritz HelmstaedterAbstract:Stimulation of a principal whisker yields sparse action potential (AP) spiking in layer 2/3 (L2/3) pyramidal neurons in a Cortical Column of rat barrel cortex. The low AP rates in pyramidal neurons could be explained by activation of interneurons in L2/3 providing inhibition onto L2/3 pyramidal neurons. L2/3 interneurons classified as local inhibitors based on their axonal projection in the same Column were reported to receive strong excitatory input from spiny neurons in L4, which are also the main source of the excitatory input to L2/3 pyramidal neurons. Here, we investigated the remaining synaptic connection in this intraColumnar microcircuit. We found strong and reliable inhibitory synaptic transmission between intraColumnar L2/3 local-inhibitor-to-L2/3 pyramidal neuron pairs [inhibitory postsynaptic potential (IPSP) amplitude -0.88 ± 0.67 mV]. On average, 6.2 ± 2 synaptic contacts were made by L2/3 local inhibitors onto L2/3 pyramidal neurons at 107 ± 64 µm path distance from the pyramidal neuron soma, thus overlapping with the distribution of synaptic contacts from L4 spiny neurons onto L2/3 pyramidal neurons (67 ± 34 µm). Finally, using compartmental simulations, we determined the synaptic conductance per synaptic contact to be 0.77 ± 0.4 nS. We conclude that the synaptic circuit from L4 to L2/3 can provide efficient shunting inhibition that is temporally and spatially aligned with the excitatory input from L4 to L2/3.
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cell type specific three dimensional structure of thalamoCortical circuits in a Column of rat vibrissal cortex
Cerebral Cortex, 2012Co-Authors: Marcel Oberlaender, Randy M. Bruno, Christiaan P. J. De Kock, Moritz Helmstaedter, Hanno S Meyer, Alejandro Ramirez, Vincent J Dercksen, Bert SakmannAbstract:Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory-evoked spiking. Here, we reconstruct the 3D circuits formed by thalamoCortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined Cortical Column in rat vibrissal cortex. We objectively classify 9 Cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamoCortical synapses. Somata and dendrites of most cell types intermingle, while thalamoCortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamoCortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location-specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type-specific lemniscal synaptic wiring diagram and elucidates structure-function relationships of this physiologically relevant pathway at single-cell resolution.
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Inhibitory interneurons in a Cortical Column form hot zones of inhibition in layers 2 and 5A
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Hanno S Meyer, Bert Sakmann, Verena C. Wimmer, Arno C Schmitt, Daniel Schwarz, Jason N D Kerr, Moritz HelmstaedterAbstract:Although physiological data on microcircuits involving a few inhibitory neurons in the mammalian cerebral cortex are available, data on the quantitative relation between inhibition and excitation in Cortical circuits involving thousands of neurons are largely missing. Because the distribution of neurons is very inhomogeneous in the cerebral cortex, it is critical to map all neurons in a given volume rather than to rely on sparse sampling methods. Here, we report the comprehensive mapping of interneurons (INs) in Cortical Columns of rat somatosensory cortex, immunolabeled for neuron-specific nuclear protein and glutamate decarboxylase. We found that a Column contains ∼2,200 INs (11.5% of ∼19,000 neurons), almost a factor of 2 less than previously estimated. The density of GABAergic neurons was inhomogeneous between layers, with peaks in the upper third of L2/3 and in L5A. IN density therefore defines a distinct layer 2 in the sensory neocortex. In addition, immunohistochemical markers of IN subtypes were layer-specific. The “hot zones” of inhibition in L2 and L5A match the reported low stimulus-evoked spiking rates of excitatory neurons in these layers, suggesting that these inhibitory hot zones substantially suppress activity in the neocortex.
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cell type specific thalamic innervation in a Column of rat vibrissal cortex
Cerebral Cortex, 2010Co-Authors: H S Meyer, Bert Sakmann, Verena C. Wimmer, Randy M. Bruno, Christiaan P. J. De Kock, Mike Hemberger, Andreas Frick, Moritz HelmstaedterAbstract:This is the concluding article in a series of 3 studies that investigate the anatomical determinants of thalamoCortical (TC) input to excitatory neurons in a Cortical Column of rat primary somatosensory cortex (S1). We used viral synaptophysin-enhanced green fluorescent protein expression in thalamic neurons and reconstructions of biocytin-labeled Cortical neurons in TC slices to quantify the number and distribution of boutons from the ventral posterior medial (VPM) and posteromedial (POm) nuclei potentially innervating dendritic arbors of excitatory neurons located in layers (L)2-6 of a Cortical Column in rat somatosensory cortex. We found that 1) all types of excitatory neurons potentially receive substantial TC input (90-580 boutons per neuron); 2) pyramidal neurons in L3-L6 receive dual TC input from both VPM and POm that is potentially of equal magnitude for thick-tufted L5 pyramidal neurons (ca. 300 boutons each from VPM and POm); 3) L3, L4, and L5 pyramidal neurons have multiple (2-4) subcellular TC innervation domains that match the dendritic compartments of pyramidal cells; and 4) a subtype of thick-tufted L5 pyramidal neurons has an additional VPM innervation domain in L4. The multiple subcellular TC innervation domains of L5 pyramidal neurons may partly explain their specific action potential patterns observed in vivo. We conclude that the substantial potential TC innervation of all excitatory neuron types in a Cortical Column constitutes an anatomical basis for the initial near-simultaneous representation of a sensory stimulus in different neuron types.
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axons predict neuronal connectivity within and between Cortical Columns and serve as primary classifiers of interneurons in a Cortical Column
2010Co-Authors: Moritz Helmstaedter, Dirk FeldmeyerAbstract:The axonal projections of nerve cells have been used to infer synaptic connectivity ever since the drawings of Ramon y Cajal more than a hundred years ago. Here we review the assumptions behind these studies and report how axonal projections of thalamic and Cortical neurons can be used to anatomically define Cortical Columns as innervation volumes in rat barrel cortex. We then apply this analysis to Cortical interneurons and illustrate that it is the axonal projections of interneurons which best permit their functional classification with reference to Cortical Columns. We conclude that the axons of Cortical nerve cells should serve as their primary classifiers, because they best indicate their function in the neoCortical neuronal network.
Dirk Feldmeyer - One of the best experts on this subject based on the ideXlab platform.
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axons predict neuronal connectivity within and between Cortical Columns and serve as primary classifiers of interneurons in a Cortical Column
2010Co-Authors: Moritz Helmstaedter, Dirk FeldmeyerAbstract:The axonal projections of nerve cells have been used to infer synaptic connectivity ever since the drawings of Ramon y Cajal more than a hundred years ago. Here we review the assumptions behind these studies and report how axonal projections of thalamic and Cortical neurons can be used to anatomically define Cortical Columns as innervation volumes in rat barrel cortex. We then apply this analysis to Cortical interneurons and illustrate that it is the axonal projections of interneurons which best permit their functional classification with reference to Cortical Columns. We conclude that the axons of Cortical nerve cells should serve as their primary classifiers, because they best indicate their function in the neoCortical neuronal network.
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l2 3 interneuron groups defined by multiparameter analysis of axonal projection dendritic geometry and electrical excitability
Cerebral Cortex, 2009Co-Authors: Moritz Helmstaedter, Bert Sakmann, Dirk FeldmeyerAbstract:For a detailed description of the circuitry of Cortical Columns at the level of single neurons, it is essential to define the identities of the cell types that constitute these Columns. For interneurons (INs), we described 4 "types of axonal projection patterns" in layer 2/3 (L2/3) with reference to the outlines of a Cortical Column (Helmstaedter et al. 2008a). In addition we quantified the dendritic geometry and electrical excitability of 3 types of the L2/3 INs: "local," "lateral," and "translaminar" inhibitors (Helmstaedter et al. 2008b). Here, we used an iterated cluster analysis (iCA) that combines axonal projection patterns with dendritic geometry and electrical excitability parameters to identify "groups" of INs, from a sample of 39 cells. The iCA defined 9 groups of INs. We propose a hierarchical scheme for identifying L2/3 INs. First, L2/3 INs can be classified as 4 types of axonal projections. Second, L2/3 INs can be subclassified as 9 groups with a high within-group similarity of dendritic, axonal, and electrical parameters. This scheme of identifying L2/3 INs may help to quantitatively describe inhibitory effects on sensory stimulus representations in L2/3 of Cortical Columns.
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reconstruction of an average Cortical Column in silico
Brain Research Reviews, 2007Co-Authors: Moritz Helmstaedter, Dirk Feldmeyer, Randy M. Bruno, C P J De Kock, Bert SakmannAbstract:The characterization of individual neurons by Golgi and Cajal has been the basis of neuroanatomy for a century. A new challenge is to anatomically describe, at cellular resolution, complete local circuits that can drive behavior. In this essay, we review the possibilities to obtain a model Cortical Column by using in vitro and in vivo pair recordings, followed by anatomical reconstructions of the projecting and target cells. These pairs establish connection modules that eventually may be useful to synthesize an average Cortical Column in silico. Together with data on sensory evoked neuronal activity measured in vivo, this will allow to model the anatomical and functional cellular basis of behavior based on more realistic assumptions than previously attempted.
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Excitatory signal flow and connectivity in a Cortical Column: focus on barrel cortex
Brain Structure and Function, 2007Co-Authors: Joachim Lübke, Dirk FeldmeyerAbstract:A basic feature of the neocortex is its organization in functional, vertically oriented Columns, recurring modules of signal processing and a system of transColumnar long-range horizontal connections. These Columns, together with their network of neurons, present in all sensory cortices, are the cellular substrate for sensory perception in the brain. Cortical Columns contain thousands of neurons and span all Cortical layers. They receive input from other Cortical areas and subCortical brain regions and in turn their neurons provide output to various areas of the brain. The modular concept presumes that the neuronal network in a Cortical Column performs basic signal transformations, which are then integrated with the activity in other networks and more extended brain areas. To understand how sensory signals from the periphery are transformed into electrical activity in the neocortex it is essential to elucidate the spatial-temporal dynamics of Cortical signal processing and the underlying neuronal ‘microcircuits’. In the last decade the ‘barrel’ field in the rodent somatosensory cortex, which processes sensory information arriving from the mysticial vibrissae, has become a quite attractive model system because here the Columnar structure is clearly visible. In the neocortex and in particular the barrel cortex, numerous neuronal connections within or between Cortical layers have been studied both at the functional and structural level. Besides similarities, clear differences with respect to both physiology and morphology of synaptic transmission and connectivity were found. It is therefore necessary to investigate each neuronal connection individually, in order to develop a realistic model of neuronal connectivity and organization of a Cortical Column. This review attempts to summarize recent advances in the study of individual microcircuits and their functional relevance within the framework of a Cortical Column, with emphasis on excitatory signal flow.
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synaptic connections between layer 4 spiny neurone layer 2 3 pyramidal cell pairs in juvenile rat barrel cortex physiology and anatomy of interlaminar signalling within a Cortical Column
The Journal of Physiology, 2002Co-Authors: Dirk Feldmeyer, Joachim H R Lubke, Angus R Silver, Bert SakmannAbstract:Whole-cell voltage recordings were obtained from 64 synaptically coupled excitatory layer 4 (L4) spiny neurones and L2/3 pyramidal cells in acute slices of the somatosensory cortex ('barrel' cortex) of 17- to 23-days-old rats. Single action potentials (APs) in the L4 spiny neurone evoked single unitary EPSPs in the L2/3 pyramidal cell with a peak amplitude of 0.7 +/- 0.6 mV. The average latency was 2.1 +/- 0.6 ms, the rise time was 0.8 +/- 0.3 ms and the decay time constant was 12.7 +/- 3.5 ms. The percentage of failures of an AP in a L4 spiny neurone to evoke a unitary EPSP in the L2/3 pyramidal cell was 4.9 +/- 8.8 % and the coefficient of variation (c.v.) of the unitary EPSP amplitude was 0.27 +/- 0.13. Both c.v. and percentage of failures decreased with increased average EPSP amplitude. Postsynaptic glutamate receptors (GluRs) in L2/3 pyramidal cells were of the N-methyl-D-aspartate (NMDA) receptor (NMDAR) and the non-NMDAR type. At -60 mV in the presence of extracellular Mg2+ (1 mM), 29 +/- 15 % of the EPSP voltage-time integral was blocked by NMDAR antagonists. In 0 Mg2+, the NMDAR/AMPAR ratio of the EPSC was 0.50 +/- 0.29, about half the value obtained for L4 spiny neurone connections. Burst stimulation of L4 spiny neurones showed that EPSPs in L2/3 pyramidal cells depressed over a wide range of frequencies (1-100 s(-1) ). However, at higher frequencies (30 s(-1)) EPSP summation overcame synaptic depression so that the summed EPSP was larger than the first EPSP amplitude in the train. The number of putative synaptic contacts established by the axonal collaterals of the L4 projection neurone with the target neurone in layer 2/3 varied between 4 and 5, with an average of 4.5 +/- 0.5 (n = 13 pairs). Synapses were established on basal dendrites of the pyramidal cell. Their mean geometric distance from the pyramidal cell soma was 67 +/- 34 microm (range, 16-196 microm). The results suggest that each connected L4 spiny neurone produces a weak but reliable EPSP in the pyramidal cell. Therefore transmission of signals to layer 2/3 is likely to have a high threshold requiring simultaneous activation of many L4 neurons, implying that L4 spiny neurone to L2/3 pyramidal cell synapses act as a gate for the lateral spread of excitation in layer 2/3.
Randy M. Bruno - One of the best experts on this subject based on the ideXlab platform.
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deep Cortical layers are activated directly by thalamus
Science, 2013Co-Authors: Christine M Constantinople, Randy M. BrunoAbstract:The thalamoCortical (TC) projection to layer 4 (L4) is thought to be the main route by which sensory organs communicate with cortex. Sensory information is believed to then propagate through the Cortical Column along the L4→L2/3→L5/6 pathway. Here, we show that sensory-evoked responses of L5/6 neurons in rats derive instead from direct TC synapses. Many L5/6 neurons exhibited sensory-evoked postsynaptic potentials with the same latencies as L4. Paired in vivo recordings from L5/6 neurons and thalamic neurons revealed substantial convergence of direct TC synapses onto diverse types of infragranular neurons, particularly in L5B. Pharmacological inactivation of L4 had no effect on sensory-evoked synaptic input to L5/6 neurons. L4 is thus not an obligatory distribution hub for Cortical activity, and thalamus activates two separate, independent "strata" of cortex in parallel.
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cell type specific three dimensional structure of thalamoCortical circuits in a Column of rat vibrissal cortex
Cerebral Cortex, 2012Co-Authors: Marcel Oberlaender, Randy M. Bruno, Christiaan P. J. De Kock, Moritz Helmstaedter, Hanno S Meyer, Alejandro Ramirez, Vincent J Dercksen, Bert SakmannAbstract:Soma location, dendrite morphology, and synaptic innervation may represent key determinants of functional responses of individual neurons, such as sensory-evoked spiking. Here, we reconstruct the 3D circuits formed by thalamoCortical afferents from the lemniscal pathway and excitatory neurons of an anatomically defined Cortical Column in rat vibrissal cortex. We objectively classify 9 Cortical cell types and estimate the number and distribution of their somata, dendrites, and thalamoCortical synapses. Somata and dendrites of most cell types intermingle, while thalamoCortical connectivity depends strongly upon the cell type and the 3D soma location of the postsynaptic neuron. Correlating dendrite morphology and thalamoCortical connectivity to functional responses revealed that the lemniscal afferents can account for some of the cell type- and location-specific subthreshold and spiking responses after passive whisker touch (e.g., in layer 4, but not for other cell types, e.g., in layer 5). Our data provides a quantitative 3D prediction of the cell type-specific lemniscal synaptic wiring diagram and elucidates structure-function relationships of this physiologically relevant pathway at single-cell resolution.
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cell type specific thalamic innervation in a Column of rat vibrissal cortex
Cerebral Cortex, 2010Co-Authors: H S Meyer, Bert Sakmann, Verena C. Wimmer, Randy M. Bruno, Christiaan P. J. De Kock, Mike Hemberger, Andreas Frick, Moritz HelmstaedterAbstract:This is the concluding article in a series of 3 studies that investigate the anatomical determinants of thalamoCortical (TC) input to excitatory neurons in a Cortical Column of rat primary somatosensory cortex (S1). We used viral synaptophysin-enhanced green fluorescent protein expression in thalamic neurons and reconstructions of biocytin-labeled Cortical neurons in TC slices to quantify the number and distribution of boutons from the ventral posterior medial (VPM) and posteromedial (POm) nuclei potentially innervating dendritic arbors of excitatory neurons located in layers (L)2-6 of a Cortical Column in rat somatosensory cortex. We found that 1) all types of excitatory neurons potentially receive substantial TC input (90-580 boutons per neuron); 2) pyramidal neurons in L3-L6 receive dual TC input from both VPM and POm that is potentially of equal magnitude for thick-tufted L5 pyramidal neurons (ca. 300 boutons each from VPM and POm); 3) L3, L4, and L5 pyramidal neurons have multiple (2-4) subcellular TC innervation domains that match the dendritic compartments of pyramidal cells; and 4) a subtype of thick-tufted L5 pyramidal neurons has an additional VPM innervation domain in L4. The multiple subcellular TC innervation domains of L5 pyramidal neurons may partly explain their specific action potential patterns observed in vivo. We conclude that the substantial potential TC innervation of all excitatory neuron types in a Cortical Column constitutes an anatomical basis for the initial near-simultaneous representation of a sensory stimulus in different neuron types.
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Dimensions of a projection Column and architecture of VPM and POm axons in rat vibrissal cortex.
Cerebral Cortex, 2010Co-Authors: Verena C. Wimmer, Randy M. Bruno, Christiaan P. J. De Kock, Thomas Kuner, Bert SakmannAbstract:This is the first article in a series of 3 studies that investigate the anatomical determinants of thalamoCortical (TC) input to excitatory neurons in a Cortical Column of rat primary somatosensory cortex (S1). S1 receives 2 major types of TC inputs, lemiscal and paralemniscal. Lemiscal axons arise from the ventral posteromedial nucleus (VPM) of the thalamus, whereas paralemniscal fibers originate in the posteromedial nucleus (POm). While these 2 TC projections are largely complementary in L4, overlap in other Cortical layers is still a matter of debate. VPM and POm axons were specifically labeled in the same rat by virus-mediated expression of different fluorescent proteins. We show that Columnar and septal projection patterns are maintained throughout most of the Cortical depth with a lower degree of separation in infragranular layers, where TC axons form bands along rows. Finally, we present anatomical dimensions of "TC projection domains" for a standard Column in S1.
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reconstruction of an average Cortical Column in silico
Brain Research Reviews, 2007Co-Authors: Moritz Helmstaedter, Dirk Feldmeyer, Randy M. Bruno, C P J De Kock, Bert SakmannAbstract:The characterization of individual neurons by Golgi and Cajal has been the basis of neuroanatomy for a century. A new challenge is to anatomically describe, at cellular resolution, complete local circuits that can drive behavior. In this essay, we review the possibilities to obtain a model Cortical Column by using in vitro and in vivo pair recordings, followed by anatomical reconstructions of the projecting and target cells. These pairs establish connection modules that eventually may be useful to synthesize an average Cortical Column in silico. Together with data on sensory evoked neuronal activity measured in vivo, this will allow to model the anatomical and functional cellular basis of behavior based on more realistic assumptions than previously attempted.
Christof Koch - One of the best experts on this subject based on the ideXlab platform.
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the computational properties of a simplified Cortical Column model
PLOS Computational Biology, 2016Co-Authors: Nicholas Cain, Ramakrishnan Iyer, Christof Koch, Stefan MihalasAbstract:The mammalian neocortex has a repetitious, laminar structure and performs functions integral to higher cognitive processes, including sensory perception, memory, and coordinated motor output. What computations does this circuitry subserve that link these unique structural elements to their function? Potjans and Diesmann (2014) parameterized a four-layer, two cell type (i.e. excitatory and inhibitory) model of a Cortical Column with homogeneous populations and cell type dependent connection probabilities. We implement a version of their model using a displacement integro-partial differential equation (DiPDE) population density model. This approach, exact in the limit of large homogeneous populations, provides a fast numerical method to solve equations describing the full probability density distribution of neuronal membrane potentials. It lends itself to quickly analyzing the mean response properties of population-scale firing rate dynamics. We use this strategy to examine the input-output relationship of the Potjans and Diesmann Cortical Column model to understand its computational properties. When inputs are constrained to jointly and equally target excitatory and inhibitory neurons, we find a large linear regime where the effect of a multi-layer input signal can be reduced to a linear combination of component signals. One of these, a simple subtractive operation, can act as an error signal passed between hierarchical processing stages.
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POSTER PRESENTATION Open Access The computational properties of a simplified Cortical
2016Co-Authors: Column Model, Nicholas Cain, Christof Koch, Ram Iyer, Stefan MihalasAbstract:The mammalian neocortex generally has a repetitious, laminar structure and performs functions integral to higher cognitive processes, including sensory percep-tion, memory, and coordinated motor output. What computations does this circuitry subserve, that might connect these unique structural elements with their biological function? Potjans and Diesmann [1] para-meterize a four- layer, two cell-type (i.e excitatory and inhibitory) model of a Cortical Column. Beginning with their detailed model description, we implement their model using a displacement PDE (DiPDE) population statistic approach. This approach affords fast semi-analytic numerical method to solve equations describ-ing homogeneous neuronal populations [2] (see also [3])
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physiology of layer 5 pyramidal neurons in mouse primary visual cortex coincidence detection through bursting
PLOS Computational Biology, 2015Co-Authors: Adam S Shai, Matthew E Larkum, Costas A Anastassiou, Christof KochAbstract:L5 pyramidal neurons are the only neoCortical cell type with dendrites reaching all six layers of cortex, casting them as one of the main integrators in the Cortical Column. What is the nature and mode of computation performed in mouse primary visual cortex (V1) given the physiology of L5 pyramidal neurons? First, we experimentally establish active properties of the dendrites of L5 pyramidal neurons of mouse V1 using patch-clamp recordings. Using a detailed multi-compartmental model, we show this physiological setup to be well suited for coincidence detection between basal and apical tuft inputs by controlling the frequency of spike output. We further show how direct inhibition of calcium channels in the dendrites modulates such coincidence detection. To establish the singe-cell computation that this biophysics supports, we show that the combination of frequency-modulation of somatic output by tuft input and (simulated) calcium-channel blockage functionally acts as a composite sigmoidal function. Finally, we explore how this computation provides a mechanism whereby dendritic spiking contributes to orientation tuning in pyramidal neurons.
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the computational properties of a simplified Cortical Column model
BMC Neuroscience, 2014Co-Authors: Nicholas Cain, Ramakrishnan Iyer, Christof Koch, Stefan MihalasAbstract:The mammalian neocortex generally has a repetitious, laminar structure and performs functions integral to higher cognitive processes, including sensory perception, memory, and coordinated motor output. What computations does this circuitry subserve, that might connect these unique structural elements with their biological function? Potjans and Diesmann [1] parameterize a four- layer, two cell-type (i.e excitatory and inhibitory) model of a Cortical Column. Beginning with their detailed model description, we implement their model using a displacement PDE (DiPDE) population statistic approach. This approach affords fast semi-analytic numerical method to solve equations describing homogeneous neuronal populations [2] (see also [3]). This population statistic approach lends itself to quickly analyzing the response properties of population-scale dynamics of neural tissue. We use this strategy to examine the input-output relationship of the Potjans and Diesmann Column model (see also [4]), in an attempt to uncover canonical computations [5] that it might implement. We find that excitatory perturbations to layers 4 (a site of primarily ”bottom-up” thalamic input in sensory areas) and 2/3 (a site of primarily ”top-down” Cortical input) elicit an attenuated, additive perturbation in layer 23 activity, yet offset subtractively in their effect on layer 5 (see Figure Figure1).1). This computation might subserve, for example, an inferential update of prior experience with new sensory information. We generalize this finding by computing a linear kernel that describes the response of the Column circuit to time varying stimuli. Figure 1 The effect of excitatory perturbations on the firing rate of subpopulations of the Cortical Column model. Three different excitatory perturbations of 20 Hz were applied to layers of the model. The first two excited neurons in only layer 2/3, while the ...
