Patrik Krieger

Publications (11)47.2 Total impact

• Article: RipleyGUI: software for analyzing spatial patterns in 3D cell distributions.

  Kristin Hansson, Mehrdad Jafari-Mamaghani, Patrik Krieger
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  ABSTRACT: The true revolution in the age of digital neuroanatomy is the ability to extensively quantify anatomical structures and thus investigate structure-function relationships in great detail. To facilitate the quantification of neuronal cell patterns we have developed RipleyGUI, a MATLAB-based software that can be used to detect patterns in the 3D distribution of cells. RipleyGUI uses Ripley's K-function to analyze spatial distributions. In addition the software contains statistical tools to determine quantitative statistical differences, and tools for spatial transformations that are useful for analyzing non-stationary point patterns. The software has a graphical user interface making it easy to use without programming experience, and an extensive user manual explaining the basic concepts underlying the different statistical tools used to analyze spatial point patterns. The described analysis tool can be used for determining the spatial organization of neurons that is important for a detailed study of structure-function relationships. For example, neocortex that can be subdivided into six layers based on cell density and cell types can also be analyzed in terms of organizational principles distinguishing the layers.
  Frontiers in Neuroinformatics 01/2013; 7:5.
• Source

  Available from: PubMed Central

  Article: Spatial Point Pattern Analysis of Neurons Using Ripley's K-Function in 3D.

  Mehrdad Jafari-Mamaghani, Mikael Andersson, Patrik Krieger
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  ABSTRACT: The aim of this paper is to apply a non-parametric statistical tool, Ripley's K-function, to analyze the 3-dimensional distribution of pyramidal neurons. Ripley's K-function is a widely used tool in spatial point pattern analysis. There are several approaches in 2D domains in which this function is executed and analyzed. Drawing consistent inferences on the underlying 3D point pattern distributions in various applications is of great importance as the acquisition of 3D biological data now poses lesser of a challenge due to technological progress. As of now, most of the applications of Ripley's K-function in 3D domains do not focus on the phenomenon of edge correction, which is discussed thoroughly in this paper. The main goal is to extend the theoretical and practical utilization of Ripley's K-function and corresponding tests based on bootstrap resampling from 2D to 3D domains.
  Frontiers in Neuroinformatics 01/2010; 4:9.
• Article: Experience-dependent increase in spine calcium evoked by backpropagating action potentials in layer 2/3 pyramidal neurons in rat somatosensory cortex.

  Patrik Krieger
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  ABSTRACT: In spines on basal dendrites of layer 2/3 pyramidal neurons in somatosensory barrel cortex, calcium transients evoked by back-propagating action potentials (bAPs) were investigated (i) along the length of the basal dendrite, (ii) with postnatal development and (iii) with sensory deprivation during postnatal development. Layer 2/3 pyramidal neurons were investigated at three different ages. At all ages [postnatal day (P)8, P14, P21] the bAP-evoked calcium transient amplitude increased with distance from the soma with a peak at around 50 microm, followed by a gradual decline in amplitude. The effect of sensory deprivation on the bAP-evoked calcium was investigated using two different protocols. When all whiskers on one side of the rat snout were trimmed daily from P8 to P20-24 there was no difference in the bAP-evoked calcium transient between cells in the contralateral hemisphere, lacking sensory input from the whisker, and cells in the ipsilateral barrel cortex, with intact whisker activation. When, however, only the D-row whiskers on one side were trimmed the distribution of bAP-evoked calcium transients in spines was shifted towards larger amplitudes in cells located in the deprived D-column. In conclusion, (i) the bAP-evoked calcium transient gradient along the dendrite length is established at P8, (ii) the calcium transient increases in amplitude with age and (iii) this increase is enhanced in layer 2/3 pyramidal neurons located in a sensory-deprived barrel column that is bordered by non-deprived barrel columns.
  European Journal of Neuroscience 11/2009; 30(10):1870-7. · 3.63 Impact Factor
• Article: Cell-type specific properties of pyramidal neurons in neocortex underlying a layout that is modifiable depending on the cortical area.

  Alexander Groh, Hanno S Meyer, Eric F Schmidt, Nathaniel Heintz, Bert Sakmann, Patrik Krieger
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  ABSTRACT: To understand sensory representation in cortex, it is crucial to identify its constituent cellular components based on cell-type-specific criteria. With the identification of cell types, an important question can be addressed: to what degree does the cellular properties of neurons depend on cortical location? We tested this question using pyramidal neurons in layer 5 (L5) because of their role in providing major cortical output to subcortical targets. Recently developed transgenic mice with cell-type-specific enhanced green fluorescent protein labeling of neuronal subtypes allow reliable identification of 2 cortical cell types in L5 throughout the entire neocortex. A comprehensive investigation of anatomical and functional properties of these 2 cell types in visual and somatosensory cortex demonstrates that, with important exceptions, most properties appear to be cell-type-specific rather than dependent on cortical area. This result suggests that although cortical output neurons share a basic layout throughout the sensory cortex, fine differences in properties are tuned to the cortical area in which neurons reside.
  Cerebral Cortex 08/2009; 20(4):826-36. · 6.54 Impact Factor
• Article: Identification of a molecular target for glutamate regulation of astrocyte water permeability.

  Eli Gunnarson, Marina Zelenina, Gustav Axehult, Yutong Song, Alexander Bondar, Patrik Krieger, Hjalmar Brismar, Sergey Zelenin, Anita Aperia
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  ABSTRACT: Astrocytes play a key role for maintenance of brain water homeostasis, but little is known about mechanisms of short-term regulation of astrocyte water permeability. Here, we report that glutamate increases astrocyte water permeability and that the molecular target for this effect is the aquaporin-4 (AQP4) serine 111 residue, which is in a strategic position for control of the water channel gating. The glutamate effect involves activation of group I metabotropic glutamate receptors (mGluR), intracellular calcium release, and activation of calcium/calmodulin-dependent protein kinase II (CaMKII) and nitric oxide synthase (NOS). The physiological impact of our results is underlined by the finding that mGluR activation increases the rate of hypoosmotic tissue swelling in acute rat hippocampal slices. Cerebral ischemia is associated with an excessive release of glutamate, and in postischemic cerebral edema ablation of AQP4 attenuates the degree of damage. Thus, we have identified AQP4 as the molecular target for drugs that may attenuate the development of brain edema.
  Glia 05/2008; 56(6):587-96. · 4.82 Impact Factor
• Article: Synaptic connections between layer 5B pyramidal neurons in mouse somatosensory cortex are independent of apical dendrite bundling.

  Patrik Krieger, Thomas Kuner, Bert Sakmann
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  ABSTRACT: Rodent somatosensory barrel cortex is organized both physiologically and anatomically in columns with a cross-sectional diameter of 100-400 microm. The underlying anatomical correlate of physiologically defined, much narrower minicolumns (20-60 microm in diameter) remains unclear. The minicolumn has been proposed to be a fundamental functional unit in the cortex, and one anatomical component of a minicolumn is thought to be a cluster of pyramidal cells in layer 5B (L5B) that contribute their apical dendrite to distinct bundles. In transgenic mice with fluorescently labeled L5B pyramidal cells, which project to the pons and thalamus, we investigated whether the pyramidal cells of a cluster also share functional properties. We found that apical dendrite bundles in the transgenic mice were anatomically similar to apical dendrite bundles previously proposed to be part of minicolumns. We made targeted whole-cell recordings in acute brain slices from pairs of fluorescently labeled L5B pyramidal cells that were located either in the same cluster or in adjacent clusters and subsequently reconstructed their dendritic arbors. Pyramids within the same cluster had larger common dendritic domains compared with pyramids in adjacent clusters but did not receive more correlated synaptic inputs. L5B pyramids within and between clusters have similar connection probabilities and unitary EPSP amplitudes. Furthermore, intrinsically bursting and regular spiking pyramidal cells were both present within the same cluster. In conclusion, intrinsic electrical excitability and the properties of synaptic connections between this subtype of L5B pyramidal cells are independent of the cell clusters defined by bundling of their apical dendrites.
  Journal of Neuroscience 11/2007; 27(43):11473-82. · 7.11 Impact Factor
• Article: Na,K-ATPase generates calcium oscillations in hippocampal astrocytes.

  Xiao Li Liu, Ayako Miyakawa, Anita Aperia, Patrik Krieger
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  ABSTRACT: Na,K-ATPase maintains not only ionic homeostasis, but also participates in a multiprotein complex mediating intracellular signalling. We show that ouabain, a specific ligand for Na,K-ATPase, evokes calcium oscillations in hippocampal astrocytes in primary cultures. Coimmunoprecipitation studies suggest that the mechanism underlying these calcium oscillations involves a multiprotein complex consisting of ankyrin-B, the inositol 1,4,5-trisphosphate receptor and Na,K-ATPase. The ouabain/Na,K-ATPase multi-protein complex induced calcium-dependent downstream activation of the transcription factor nuclear factor-kappaB. Calcium oscillations and nuclear factor-kappaB activation were blocked following intracellular calcium store depletion. Thus, the specific Na,K-ATPase ligand ouabain induced inositol 1,4,5-trisphosphate receptor-dependent calcium oscillations in hippocampal astrocytes, which mediates nuclear factor-kappaB activation.
  Neuroreport 05/2007; 18(6):597-600. · 1.66 Impact Factor
• Article: Imaging synaptic inhibition in transgenic mice expressing the chloride indicator, Clomeleon.

  Ken Berglund, Wolfram Schleich, Patrik Krieger, Li Shen Loo, Dongqing Wang, Nell B Cant, Guoping Feng, George J Augustine, Thomas Kuner
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  ABSTRACT: We describe here a molecular genetic approach for imaging synaptic inhibition. The thy-1 promoter was used to express high levels of Clomeleon, a ratiometric fluorescent indicator for chloride ions, in discrete populations of neurons in the brains of transgenic mice. Clomeleon was functional after chronic expression and provided non-invasive readouts of intracellular chloride concentration ([Cl(-)](i)) in brain slices, allowing us to quantify age-dependent declines in resting [Cl(-)](i) during neuronal development. Activation of hippocampal interneurons caused [Cl(-)](i) to rise transiently in individual postsynaptic pyramidal neurons. [Cl(-)](i) increased in direct proportion to the amount of inhibitory transmission, with peak changes as large as 4 mM. Integrating responses over populations of pyramidal neurons allowed sensitive detection of synaptic inhibition. Thus, Clomeleon imaging permits non-invasive, spatiotemporally resolved recordings of [Cl(-)](i) in a large variety of neurons, opening up new opportunities for imaging synaptic inhibition and other forms of chloride signaling.
  Brain Cell Biology 01/2007; 35(4-6):207-28. · 3.25 Impact Factor
• Article: Metabotropic glutamate receptors provide intrinsic modulation of the lamprey locomotor network.

  Abdeljabbar El Manira, Petronella Kettunen, Dietmar Hess, Patrik Krieger
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  ABSTRACT: Spinal networks generate the motor pattern underlying locomotion. These are subject to modulatory systems that influence their operation and thereby result in a flexible network organization. In this review, we have summarized the mechanisms by which the different metabotropic glutamate receptor subtypes fine-tune the cellular and synaptic properties and thus underlie intrinsic modulation of the activity of the locomotor network in the lamprey.
  Brain Research Reviews 11/2002; 40(1-3):9-18. · 10.34 Impact Factor
• Article: Group III mGluR-mediated depression of sensory synaptic transmission.

  Patrik Krieger, Abdeljabbar El Manira
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  ABSTRACT: The effect of L-AP4, a group III mGluR agonist, on sensory synaptic transmission in the lamprey spinal cord has been analyzed. Paired recordings were made between cutaneous mechanosensory neurons (dorsal cells) and postsynaptic spinobulbar giant interneurons. L-AP4 reduced the monosynaptic dorsal cell-evoked EPSP, but at concentrations higher (200-500 microM) than those necessary to depress reticulospinal axon-evoked EPSPs. Stimulation of the dorsal column, which contains dorsal cell axons and the axons of putative nociceptive and theromosensory axons, elicited compound EPSPs that were consistently depressed by L-AP4. Sensory inputs in the lamprey are thus inhibited by group III mGluRs.
  Brain Research 06/2002; 937(1-2):41-4. · 2.73 Impact Factor
• Article: Signaling mechanisms of metabotropic glutamate receptor 5 subtype and its endogenous role in a locomotor network.

  Petronella Kettunen, Patrik Krieger, Dietmar Hess, Abdeljabbar El Manira
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  ABSTRACT: Metabotropic glutamate receptors (mGluRs) act as modulators in the CNS of vertebrates, but their role in motor pattern generation in particular is primarily unknown. The intracellular signaling mechanisms of the group I mGluRs (mGluR1 and mGluR5), and their endogenous role in regulating locomotor pattern generation have been investigated in the spinal cord of the lamprey. Application of the group I mGluR agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) produced oscillations of the intracellular Ca2+ concentration ([Ca2+]i) in neurons. The oscillations were blocked by the mGluR5 antagonist 2-methyl-6-(phenylethynyl)pyridine (MPEP) but not by the mGluR1 antagonist 7-(hydroxyimino)cyclopropa[b]chromen-1a-carboxylate ethyl ester. These [Ca2+]i oscillations were abolished by a phospholipase C blocker and after depletion of internal Ca2+ stores by thapsigargin but did not involve protein kinase C activation. Furthermore, they were dependent on Ca2+ influx, because no [Ca2+]i oscillations were produced by DHPG in a Ca2+-free solution or after blockade of L-type Ca2+ channels. The mGluR5 is activated by an endogenous release of glutamate during locomotion, and a receptor blockade by MPEP caused an increase in the burst frequency. Thus, our results show that mGluR5 induces [Ca2+]i oscillations and regulates the activity of locomotor networks through endogenous activation.
  Journal of Neuroscience 04/2002; 22(5):1868-73. · 7.11 Impact Factor