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  • 1.
    Andersson, Sten
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Petersson, Marcus E.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Ionic mechanisms of action potential propagation velocity changes in peripheral C-fibers. Implications for pain2012In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 13, no Suppl 1, p. P138-Article in journal (Refereed)
  • 2.
    Belic, Jovana
    et al.
    University of Belgrade, Serbia.
    Faisal, Aldo
    Imperial College London.
    The structured variability of finger coordination in daily tasks2011In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 12, p. 102-Article in journal (Refereed)
  • 3.
    Belic, Jovana
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. University of Freiburg, Germany.
    Klaus, Andreas
    National Institute of Mental Health, Bethesda, USA.
    Plenz, Dietmar
    National Institute of Mental Health, Bethesda, USA..
    Hellgren Kotaleski, Jeanette
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. Karolinska Institutet (KI), Sweden.
    Impact of inhibition in striatal decorrelation of cortical neuronal avalanches2013In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 14, p. 165-Article in journal (Refereed)
  • 4.
    Belic, Jovana
    et al.
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab. Bernstein Center Freiburg, University of Freiburg, Freiburg, 79104, Germany.
    Kumar, Arvind
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). Bernstein Center Freiburg, University of Freiburg, Freiburg, 79104, Germany.
    Hellgren Kotaleski, Jeanette
    KTH, School of Electrical Engineering and Computer Science (EECS), Computational Science and Technology (CST). KTH, Centres, Science for Life Laboratory, SciLifeLab. Department of Neuroscience, Karolinska Institute, Solna, 17177, Sweden.
    The role of striatal feedforward inhibition in propagation of cortical oscillations2017In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 18, p. 91-91Article in journal (Refereed)
    Abstract [en]

    Fast spiking interneurons (FSIs) and feedforward (FF) inhibition are a common property of neuronal networks throughout the brain and play crucial role in neural computations. For instance, in the cortex FF inhibition sets the window of temporal integration and spiking and thereby contributes to the control of firing rate and correlations [1]. In the striatum (the main input structure of the basal ganglia) despite their high firing rates and strong synapses, FSIs (comprise 1–2% of striatal neurons) do not seem to play a major role in controlling the firing of medium spiny neurons (MSNs; comprise 95% of striatal neurons) [2] and so far, it has not been possible to attribute a functional role to FSIs in the striatum. Here we use a spiking neuron network model in order to investigate how externally induced oscillations propagate through striatal circuitry. Recordings in the striatum have shown robust oscillatory activity that might be in fact cortical oscillations transmitted by the corticostriatal projections [3–5]. We propose that FSIs can perform an important role in transferring cortical oscillations to the striatum especially to those MSNs that are not directly driven by the cortical oscillations. Strong and divergent connectivity of FSIs implies that even weak oscillations in FSI population activity can be spread to the whole MSN population [6]. Further, we have identified multiple factors that influence the transfer of oscillations to MSNs. The variables such as the number of activated neurons, ongoing activity, connectivity, and synchronicity of inputs influence the transfer of oscillations by modifying the levels of feedforward and feedback inhibitions suggesting that the striatum can exploit different parameters to impact the transfer of oscillatory signals.

    References

    1. Isaacson, J. S., & Scanziani, M. (2011). How inhibition shapes cortical activity. Neuron, 72(2), 231–243. 

    2. Berke, J. D. (2011). Functional properties of striatal fast-spiking interneurons. Frontiers in systems neuroscience, 5.

    3. Belić, J. J., Halje, P., Richter, U., Petersson, P., & Kotaleski, J. H. (2016). Untangling cortico-striatal connectivity and cross-frequency coupling in L-DOPA-induced dyskinesia. Frontiers in systems neuroscience, 10.

    4. Berke, J. D. (2009). Fast oscillations in cortical‐striatal networks switch frequency following rewarding events and stimulant drugs. European Journal of Neuroscience, 30(5), 848–859.

    5. Boraud, T., Brown, P., Goldberg, J. A., Graybiel, A. M., & Magill, P. J. (2005). Oscillations in the basal ganglia: the good, the bad, and the unexpected. In The basal ganglia VIII (pp. 1–24). Springer US.

    6. Belić, J. J., Kumar, A., & Kotaleski, J. H. (2017). Interplay between periodic stimulation and GABAergic inhibition in striatal network oscillations. PloS one, 12(4), e0175135.

  • 5.
    Blom, Hans
    et al.
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Ronnlund, Daniel
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Scott, Lena
    Spicarova, Zuzana
    Widengren, Jerker
    KTH, School of Engineering Sciences (SCI), Applied Physics, Experimental Biomolecular Physics.
    Bondar, Alexander
    Aperia, Anita
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics.
    Spatial distribution of Na+-K+-ATPase in dendritic spines dissected by nanoscale superresolution STED microscopy2011In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 12, p. 16-Article in journal (Refereed)
    Abstract [en]

    Background: The Na+,K+-ATPase plays an important role for ion homeostasis in virtually all mammalian cells, including neurons. Despite this, there is as yet little known about the isoform specific distribution in neurons. Results: With help of superresolving stimulated emission depletion microscopy the spatial distribution of Na+,K+-ATPase in dendritic spines of cultured striatum neurons have been dissected. The found compartmentalized distribution provides a strong evidence for the confinement of neuronal Na+,K+-ATPase (alpha 3 isoform) in the postsynaptic region of the spine. Conclusions: A compartmentalized distribution may have implications for the generation of local sodium gradients within the spine and for the structural and functional interaction between the sodium pump and other synaptic proteins. Superresolution microscopy has thus opened up a new perspective to elucidate the nature of the physiological function, regulation and signaling role of Na+,K+-ATPase from its topological distribution in dendritic spines.

  • 6.
    Lindahl, Mikael
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Hellgren Kotaleski, Jeanette
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Short term plasticity within the basal ganglia - a systems level computational investigation2011In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 12, no Suppl 1, p. P145-Article in journal (Refereed)
    Abstract [en]

    Striatal direct pathway medium spiny neurons (MSNs) converge, with inhibitory synapses onto output nuclei substantia nigra reticulata (SNr), which keep neurons in the thalamus, superior colliculus and pendunculopontine nuclei under tonic inhibition[1]. Recent experimental findings[2] have found short term facilitation in MSN synapses onto SNr neurons. We investigate the functional consequences of these findings using a basal ganglia system level model, with spiking MSNs modeled according to Izhikevich’s simple model[3] and with facilitating synapses[4] fitted to data in[2]. The model is implemented in the NEST[5] simulator. We quantify how striatal populations of MSNs can control activity in SNr neurons, and to what extent this depends on having weak static, strong static and facilitating synapses between MSNs and SNr neurons.

    Our simulation experiments predict that facilitating synapses allow baseline firing of presynaptic MSNs without suppressing target SNr neurons, while burst activation of only a few of these presynaptic striatal neurons can suppress the activity of one SNr neuron. This is in accordance with extracellular recordings in awake animals[6], where task dependent activity is transferred from a broad striatal population to a smaller subpopulation, responding increasingly stronger during learning of a task dependent behavior.

  • 7.
    Nazem, Ali
    et al.
    KTH, School of Computer Science and Communication (CSC), Computer Vision and Active Perception, CVAP.
    Kootstra, Geert
    KTH, School of Computer Science and Communication (CSC), Computer Vision and Active Perception, CVAP.
    Kragic, Danica
    KTH, School of Computer Science and Communication (CSC), Computer Vision and Active Perception, CVAP.
    Djurfeldt, Mikael
    KTH, School of Computer Science and Communication (CSC), Centres, Centre for High Performance Computing, PDC. KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Interfacing a parallel simulation of a neuronal network to robotic hardware using MUSIC, with application to real-time figure-ground segregation.2011In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 12, no Suppl 1, p. 78-78Article in journal (Refereed)
  • 8.
    Petersson, Marcus E.
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Role of TRP channels in dendritic integration and subthreshold membrane potential plateaus2011In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 12, no Suppl 1, p. P110-Article in journal (Other academic)
  • 9.
    Sievertzon, Maria
    et al.
    KTH, School of Biotechnology (BIO).
    Wirta, Valtteri
    KTH, School of Biotechnology (BIO).
    Mercer, Alex
    Frisén, Jonas
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Gene Technology.
    Epidermal growth factor (EGF) withdrawal masks gene expression differences in the study of pituitary adenylate cyclase-activating polypeptide (PACAP) activation of primary neural stem cell proliferation2005In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 6, p. 55-Article in journal (Refereed)
    Abstract [en]

    Background: The recently discovered adult neural stem cells, which maintain continuous generation of new neuronal and glial cells throughout adulthood, are a promising and expandable source of cells for use in cell replacement therapies within the central nervous system. These cells could either be induced to proliferate and differentiate endogenously, or expanded and differentiated in culture before being transplanted into the damaged site of the brain. In order to achieve these goals effective strategies to isolate, expand and differentiate neural stem cells into the desired specific phenotypes must be developed. However, little is known as yet about the factors and mechanisms influencing these processes. It has recently been reported that pituitary adenylate cyclase-activating polypeptide (PACAP) promotes neural stem cell proliferation both in vivo and in vitro.

    Results: We used cDNA microarrays with the aim of analysing the transcriptional changes underlying PACAP induced proliferation of neural stem cells. The primary neural stem/progenitor cells used were neurospheres, generated from the lateral ventricle wall of the adult mouse brain. The results were compared to both differentiation and proliferation controls, which revealed an unexpected and significant differential expression relating to withdrawal of epidermal growth factor (EGF) from the neurosphere growth medium. The effect of EGF removal was so pronounced that it masked the changes in gene expression patterns produced by the addition of PACAP.

    Conclusion: Experimental models aiming at transcriptional analysis of induced proliferation in primary neural stem cells need to take into consideration the significant effect on transcription caused by removal of EGF. Alternatively, EGF-free culture conditions need to be developed.

  • 10.
    Sievertzon, Maria
    et al.
    KTH, School of Biotechnology (BIO), Centres, KTH Genome Center.
    Wirta, Valtteri
    KTH, School of Biotechnology (BIO), Centres, KTH Genome Center.
    Mercer, Alex
    Meletis, Konstantinos
    Erlandsson, Rikard
    Wikström, Lilian
    Frisén, Jonas
    Lundeberg, Joakim
    KTH, School of Biotechnology (BIO), Centres, KTH Genome Center.
    Transcriptome analysis in primary neural stem cells using a tag cDNA amplification method2005In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 6, no 28, p. 13-Article in journal (Refereed)
    Abstract [en]

    Background: Neural stem cells ( NSCs) can be isolated from the adult mammalian brain and expanded in culture, in the form of cellular aggregates called neurospheres. Neurospheres provide an in vitro model for studying NSC behaviour and give information on the factors and mechanisms that govern their proliferation and differentiation. They are also a promising source for cell replacement therapies of the central nervous system. Neurospheres are complex structures consisting of several cell types of varying degrees of differentiation. One way of characterising neurospheres is to analyse their gene expression profiles. The value of such studies is however uncertain since they are heterogeneous structures and different populations of neurospheres may vary significantly in their gene expression.

    Results: To address this issue, we have used cDNA microarrays and a recently reported tag cDNA amplification method to analyse the gene expression profiles of neurospheres originating from separate isolations of the lateral ventricle wall of adult mice and passaged to varying degrees. Separate isolations as well as consecutive passages yield a high variability in gene expression while parallel cultures yield the lowest variability.

    Conclusions: We demonstrate a low technical amplification variability using the employed amplification strategy and conclude that neurospheres from the same isolation and passage are sufficiently similar to be used for comparative gene expression analysis.

  • 11.
    Tigerholm, Jenny
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    KA channels reduce dendritic depolarization from synchronized synaptic input: implication for neural processing and epilepsy2008In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 9, no Suppl 1, p. P45-Article in journal (Refereed)
  • 12.
    Tigerholm, Jenny
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    KA channels suppress cellular responses to fast ripple activity – implications for epilepsy2009In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 10, no Suppl 1, p. P226-Article in journal (Refereed)
  • 13.
    Tigerholm, Jenny
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Fransén, Erik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB.
    Restoring ion channel pathology by parameter optimization2011In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 12, no Suppl 1, p. P334-Article in journal (Refereed)
  • 14.
    Tully, Philip
    et al.
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. Karolinska Institutet, Sweden; University of Edinburgh, UK.
    Lindén, Henrik
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. Karolinska Institutet, Sweden.
    Hennig, Matthias
    Lansner, Anders
    KTH, School of Computer Science and Communication (CSC), Computational Biology, CB. Stockholm University, Stockholm; Karolinska Institutet, Sweden.
    Probabilistic computation underlying sequence learning in a spiking attractor memory network2013In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, no 14 (Suppl 1)Article in journal (Refereed)
  • 15. Westin, Linda
    et al.
    Reuss, Matthias
    KTH, School of Engineering Sciences (SCI), Applied Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Lindskog, Maria
    Aperia, Anita
    Brismar, Hjalmar
    KTH, School of Engineering Sciences (SCI), Applied Physics, Cell Physics. KTH, Centres, Science for Life Laboratory, SciLifeLab.
    Nanoscopic spine localization of Norbin, an mGluR5 accessory protein2014In: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 15, p. 45-Article in journal (Refereed)
    Abstract [en]

    Background: Norbin is a neuron-specific, cytosolic protein that interacts with the metabotropic glutamate receptor 5 (mGluR5) and has a profound impact on mGluR5 signaling. Yet, little is known about its synaptic distribution. Results: Here we have analyzed the spatial relationship between Norbin, postsynaptic density protein 95 (PSD-95), actin and mGluR5 in spines using super-resolution microscopy. Norbin was found to have a high degree of colocalization with actin and a lower degree of colocalization with PSD-95. Co-immunoprecipitation studies confirmed that interaction occurs between Norbin and actin, but not between Norbin and PSD-95. Norbin was also found to have a high degree of colocalization with the perisynaptically located mGluR5. Findings based on structured illumination microscopy (3D-SIM) of exogenous expressed Norbin-GFP were confirmed by stimulated emission depletion microscopy (STED) of immunolabeled endogenous Norbin. Conclusions: Norbin associates with actin rather than with PSD-95 in dendritic spines. Results regarding protein localization and colocalization performed with conventional confocal microscopy must be interpreted with great caution. The now available super-resolution microscopy techniques provide more accurate information about sub-cellular protein localization than previously was possible.

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