Ändra sökning
Avgränsa sökresultatet
1 - 50 av 50
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf
Träffar per sida
  • 5
  • 10
  • 20
  • 50
  • 100
  • 250
Sortering
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
  • Standard (Relevans)
  • Författare A-Ö
  • Författare Ö-A
  • Titel A-Ö
  • Titel Ö-A
  • Publikationstyp A-Ö
  • Publikationstyp Ö-A
  • Äldst först
  • Nyast först
  • Skapad (Äldst först)
  • Skapad (Nyast först)
  • Senast uppdaterad (Äldst först)
  • Senast uppdaterad (Nyast först)
  • Disputationsdatum (tidigaste först)
  • Disputationsdatum (senaste först)
Markera
Maxantalet träffar du kan exportera från sökgränssnittet är 250. Vid större uttag använd dig av utsökningar.
  • 1.
    Andersson, Sten
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Petersson, Marcus E.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Ionic mechanisms of action potential propagation velocity changes in peripheral C-fibers. Implications for pain2012Ingår i: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 13, nr Suppl 1, s. P138-Artikel i tidskrift (Refereegranskat)
  • 2. Cervenka, Simon
    et al.
    Varrone, Andrea
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Halldin, Christer
    Farde, Lars
    PET Studies of D2-Receptor Binding in Striatal and Extrastriatal Brain Regions: Biochemical Support In Vivo for Separate Dopaminergic Systems in Humans2010Ingår i: Synapse, ISSN 0887-4476, E-ISSN 1098-2396, Vol. 64, nr 6, s. 478-485Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Most molecular imaging studies of the dopamine (DA) system performed to date have focused on the striatum, a region receiving dense dopaminergic innervation. In clinical research on the DA D2-receptor, striatal binding has often been regarded as an index of global DA function, based on the underlying assumption of common regulatory mechanisms for receptor expression across brain regions. Recent data has challenged this view, suggesting differences in genetic regulation between striatal and extrastriatal brain regions. The relationship between binding levels in brain regions has, however, not been directly examined in the same sample. In this study, we searched for interregional correlations between DA D2-receptor availability as determined with Positron Emission Tomography in 16 control subjects. The radioligands [C-11]raclopride and [C-11]FLB 457 were used for measurements of D2-receptor binding in striatal and extrastriatal regions, respectively. No correlation was observed between D2-receptor availability in striatum and any of the extrastriatal regions, as assessed using both region of interest- and voxel-based analyses. Instead, the pattern of correlations was consistent with the model of separate dopaminergic systems as has been originally observed in rodents. These preliminary results encourage approaches searching for individual patterns of receptor binding across the whole brain volume in clinical studies on the dopamine system.

  • 3. Dickson, C. T.
    et al.
    Magistretti, J.
    Shalinsky, M. H.
    Fransén, Erik
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Hasselmo, M. E.
    Alonso, A.
    Properties and role of I-h in the pacing of subthreshold oscillations in entorhinal cortex layer II neurons2000Ingår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 83, nr 5, s. 2562-2579Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Various subsets of brain neurons express a hyperpolarization-activated inward current (I-h) that has been shown to be instrumental in pacing oscillatory activity at both a single-cell and a network level. A characteristic feature of the stellate cells (SCs) of entorhinal cortex (EC) layer II, those neurons giving rise to the main component of the perforant path input to the hippocampal formation, is their ability to generate persistent, Na+-dependent rhythmic subthreshold membrane potential oscillations, which are thought to be instrumental in implementing theta rhythmicity in the entorhinal-hippocampal network. The SCs also display a robust time-dependent inward rectification in the hyperpolarizing direction that may contribute to the generation of these oscillations. We performed whole cell recordings of SCs in in vitro slices to investigate the specific biophysical and pharmacological properties of the current underlying this inward rectification and to clarify its potential role in the genesis of the subthreshold oscillations. In voltage-clamp conditions, hyperpolarizing voltage steps evoked a slow, noninactivating inward current, which also deactivated slowly on depolarization. This current was identified as I-h because it was resistant to extracellular Ba2+, sensitive to Cs+, completely and selectively abolished by ZD7288, and carried by both Na+ and K+ ions. I-h in the SCs had an activation threshold and reversal potential at approximately -45 and -20 mV, respectively. Its half-activation voltage was -77 mV. Importantly, bath perfusion with ZD7288, but not Ba2+ gradually and completely abolished the subthreshold oscillations, thus directly implicating I-h in their generation. Using experimentally derived biophysical parameters for I-h and the low-threshold persistent Na+ current (I-NaP) present in the SCs, a simplified model of these neurons was constructed and their subthreshold electroresponsiveness simulated. This indicated that the interplay between I-NaP and I-h can sustain persistent subthreshold oscillations in SCs. I-NaP and I-h operate in a push-pull fashion where the delay in the activation/deactivation of I-h gives rise to the oscillatory process.

  • 4. Egorov, A. V.
    et al.
    Hamam, B. N.
    Fransén, Erik
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Hasselmo, M. E.
    Alonso, A. A.
    Graded persistent activity in entorhinal cortex neurons2002Ingår i: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 420, nr 6912, s. 173-178Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Working memory represents the ability of the brain to hold externally or internally driven information for relatively short periods of time(1,2). Persistent neuronal activity is the elementary process underlying working memory but its cellular basis remains unknown. The most widely accepted hypothesis is that persistent activity is based on synaptic reverberations in recurrent circuits. The entorhinal cortex in the parahippocampal region is crucially involved in the acquisition, consolidation and retrieval of long-term memory traces for which working memory operations are essential(2). Here we show that individual neurons from layer V of the entorhinal cortex-which link the hippocampus to extensive cortical regions(3)-respond to consecutive stimuli with graded changes in firing frequency that remain stable after each stimulus presentation. In addition, the sustained levels of firing frequency can be either increased or decreased in an input-specific manner. This firing behaviour displays robustness to distractors; it is linked to cholinergic muscarinic receptor activation, and relies on activity-dependent changes of a Ca2+-sensitive cationic current. Such an intrinsic neuronal ability to generate graded persistent activity constitutes an elementary mechanism for working memory.

  • 5.
    Ekeberg, Örjan
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Herman, Pawel
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Kumar, Arvind
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Lindeberg, Tony
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsvetenskap och beräkningsteknik (CST).
    Computational Brain Science at CST, CSC, KTH2016Övrigt (Övrigt vetenskapligt)
    Abstract [en]

    Mission and Vision - Computational Brain Science Lab at CST, CSC, KTH

    The scientific mission of the Computational Brain Science Lab at CSC is to be at the forefront of mathematical modelling, quantitative analysis and mechanistic understanding of brain function. We perform research on (i) computational modelling of biological brain function and on (ii) developing theory, algorithms and software for building computer systems that can perform brain-like functions. Our research answers scientific questions and develops methods in these fields. We integrate results from our science-driven brain research into our work on brain-like algorithms and likewise use theoretical results about artificial brain-like functions as hypotheses for biological brain research.

    Our research on biological brain function includes sensory perception (vision, hearing, olfaction, pain), cognition (action selection, memory, learning) and motor control at different levels of biological detail (molecular, cellular, network) and mathematical/functional description. Methods development for investigating biological brain function and its dynamics as well as dysfunction comprises biomechanical simulation engines for locomotion and voice, machine learning methods for analysing functional brain images, craniofacial morphology and neuronal multi-scale simulations. Projects are conducted in close collaborations with Karolinska Institutet and Karolinska Hospital in Sweden as well as other laboratories in Europe, U.S., Japan and India.

    Our research on brain-like computing concerns methods development for perceptual systems that extract information from sensory signals (images, video and audio), analysis of functional brain images and EEG data, learning for autonomous agents as well as development of computational architectures (both software and hardware) for neural information processing. Our brain-inspired approach to computing also applies more generically to other computer science problems such as pattern recognition, data analysis and intelligent systems. Recent industrial collaborations include analysis of patient brain data with MentisCura and the startup company 13 Lab bought by Facebook.

    Our long term vision is to contribute to (i) deeper understanding of the computational mechanisms underlying biological brain function and (ii) better theories, methods and algorithms for perceptual and intelligent systems that perform artificial brain-like functions by (iii) performing interdisciplinary and cross-fertilizing research on both biological and artificial brain-like functions. 

    On one hand, biological brains provide existence proofs for guiding our research on artificial perceptual and intelligent systems. On the other hand, applying Richard Feynman’s famous statement ”What I cannot create I do not understand” to brain science implies that we can only claim to fully understand the computational mechanisms underlying biological brain function if we can build and implement corresponding computational mechanisms on a computerized system that performs similar brain-like functions.

  • 6.
    Eriksson, David
    et al.
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Fransén, Erik
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Zilberter, Y.
    Lansner, Anders
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Effects of short-term synaptic plasticity in a local microcircuit on cell firing2003Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 52-54, s. 7-12Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Effects of short-term synaptic plasticity on cell firing properties in a microcircuit formed by a reciprocally connected pyramidal cell and FSN interneuron in layer 2/3 of neocortex were analyzed in a biophysical model. Induction of synaptic depression by backpropagating dendritic action potentials was replicated, as well as the resulting time dependent depression of IPSP amplitudes. Results indicate that the effect of the depression becomes significant above 30 Hz input frequency. The magnitude of the effect depends on the time constant of the dendritic calcium regulating the depression. The frequency range depends on the time constant of the IPSP.

  • 7.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    A synapse which can switch from inhibitory to excitatory and back2005Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 65, s. 39-45Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Co-release of transmitters has recently been observed at synapse terminals and can even be a combination such as glutamate and GABA. A second recent experimental finding is a short-term synaptic plasticity, which depends on postsynaptic depolarization releasing a dendritic transmitter, which affects presynaptic release probability. In this work we are investigating the functional consequences for a synapse if it had both co-release and conditioning depression. If initially the GABA component is larger than the glutamate component, the synapse has an inhibitory net effect. However, if the postsynaptic cell is conditioned, the GABA component will be suppressed yielding an excitatory synapse.

  • 8.
    Fransén, Erik
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Coexistence of synchronized oscillatory and desynchronized rate activity in cortical networks2003Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. apr-52, s. 763-769Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The basis of MRI and PET experiments is the finding that neuronal cell firing levels are modulated in a task dependent manner. Results from EEG and MEG experiments on the other hand point to the importance of synchrony, e.g. the peak frequency may depend on the difficulty of the task. In most models only one of these activity modes of firing is desirable or possible to produce. In this work we show how a cortical microcircuit can produce either synchronized or desynchronized firing, and how this solves problems of present day rate and synchronization models.

  • 9.
    Fransén, Erik
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Functional role of Entorhinal cortex in working memory and information processing of the medial temporal lobe2004Ingår i: 2004 IEEE INTERNATIONAL JOINT CONFERENCE ON NEURAL NETWORKS, VOLS 1-4, PROCEEDINGS, 2004, s. 621-624Konferensbidrag (Refereegranskat)
    Abstract [en]

    Our learning and memory system has the challenge to work in a world where items to learn are dispersed in space and time. From the information extracted by the perceptual systems, the learning system must select and combine information. Both these operations may require a temporary storage where significance and correlations may be assessed. This work builds on the common hypothesis that hippocampus and subicular, entorhinal and parahippocampal/postrhinal areas are essential for these functions. We bring up two examples of models, one modeling in vivo and in vitro data from entorhinal cortex layer II of delay match-to-sample working memory experiments, and one modeling slice data from layer V showing cellular "integrator-like" intrinsically generated stable graded levels of spiking activity. In both cases we discuss how cationic currents might be involved and relate their kinetics and pharmacology to behavioral and cellular experimental results.

  • 10.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Functional role of entorhinal cortex in working memory processing2005Ingår i: Neural Networks, ISSN 0893-6080, E-ISSN 1879-2782, Vol. 18, nr 9, s. 1141-1149Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Our learning and memory system has the challenge to work in a world where items to learn are dispersed in space and time. From the information extracted by the perceptual systems, the learning system must select and combine information. Both these operations may require a temporary storage where significance and correlations could be assessed. This work builds on the common hypothesis that hippocampus and subicular, entorhinal and parahippocampal/postrhinal areas are essential for the above-mentioned functions. We bring up two examples of models: the first one is modeling of in vivo and in vitro data from entorhinal cortex layer 11 of delayed match-to-sample working memory experiments, the second one studying mechanisms in theta rhythmicity in EC. In both cases, we discuss how cationic currents might be involved and relate their kinetics and pharmacology to behavioral and cellular experimental results.

  • 11.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Ionic Mechanisms in Peripheral Pain2014Ingår i: Computational Neuroscience / [ed] Blackwell, K.T., Elsevier, 2014, s. 23-51Kapitel i bok, del av antologi (Refereegranskat)
    Abstract [en]

    Chronic pain constitutes an important and growing problem in society with large unmet needs with respect to treatment and clear implications for quality of life. Computational modeling is used to complement experimental studies to elucidate mechanisms involved in pain states. Models representing the peripheral nerve ending often address questions related to sensitization or reduction in pain detection threshold. In models of the axon or the cell body of the unmyelinated C-fiber, a large body of work concerns the role of particular sodium channels and mutations of these. Furthermore, in central structures: spinal cord or higher structures, sensitization often refers not only to enhanced synaptic efficacy but also to elevated intrinsic neuronal excitability. One of the recent developments in computational neuroscience is the emergence of computational neuropharmacology. In this area, computational modeling is used to study mechanisms of pathology with the objective of finding the means of restoring healthy function. This research has received increased attention from the pharmaceutical industry as ion channels have gained increased interest as drug targets. Computational modeling has several advantages, notably the ability to provide mechanistic links between molecular and cellular levels on the one hand and functions at the systems level on the other hand. These characteristics make computational modeling an additional tool to be used in the process of selecting pharmaceutical targets. Furthermore, large-scale simulations can provide a framework to systematically study the effects of several interacting disease parameters or effects from combinations of drugs.

  • 12.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Neural response profile design: Reducing epileptogenic activity by modifying neuron responses to synchronized input using novel potassium channels obtained by parameter search optimization2007Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 70, nr 10-12, s. 1630-1634Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neurons obtain their dynamical electrical characteristics by a set of ion channels. These properties may not only affect the function of the neuron and the local network it forms part of, but it may also eventually affect behavior. We were interested to study whether epileptogenic activity could be reduced by adding an ion channel. In this work, we used computational search techniques to optimize ion channel properties for the goal of modifying neural response characteristics. Our results show that this type of parameter search is possible and reasonably efficient. Successful searches were generated using the direct method PRAXIS, and by systematic searches in low-dimensional sub-spaces. We also report on unsuccessful searches using a simplex-type method, a gradient-based method, and attempts to reduce goal function evaluation time. Importantly, using this search strategy, our study has shown that it is possible to change a neuron's characteristics selectively with regard to response to degree of synchronicity in synaptic input.

  • 13.
    Fransén, Erik A.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Mechanisms of Graded Persistent Activity: Implications for Epilepsy2008Ingår i: Computational Neuroscience in Epilepsy, Elsevier, 2008, s. 215-231Kapitel i bok, del av antologi (Övrigt vetenskapligt)
    Abstract [en]

    One major topic in epilepsy is factors contributing to neuronal excitability. This chapter considers depolarizing sources from cationic currents. These ion channels of the TRP-type are permeable to Na, K and sometimes Ca, and show a slow time dynamics. They can therefore provide the dendrites with integrative properties over seconds and perhaps even minutes. This makes them powerful as integrators of synaptic input. Further, their activation depends to a large degree on intracellular calcium. They may therefore during seizures become strongly activated and thereby further contribute to epileptogenic activity directly by depolarization and indirectly by their calcium permeability. Cationic currents are widely distributed throughout the nervous system, including cortical, cerebellar and subcortical neurons. This chapter describes the work in entorhinal cortex and, specifically, the plateau firing characteristics found in pyramidal cells of layer V. These cells show persistent action potential firing at plateaus, which may last over ten minutes. Intriguingly, these plateaus are graded in that input, synaptic or by current injection, can shift them up and down in frequency. After the original finding, graded plateaus have been found also in perirhinal cortex and amygdala. Functionally, cationic neuronal integrator capacity has been shown to be involved in sensory-motor integration. Finally, anticonvulsants like lamotrigine and phenytoin have been found to reduce depolarizations involving cationic currents. Cation currents may therefore be targets in treatments of epilepsy.

  • 14.
    Fransén, Erik
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Ahlström, Peter
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Ionic mechanisms of post spike excitability changes during high-frequency firing rates2014Ingår i: Scandinavian Journal of Pain, ISSN 1877-8860, E-ISSN 1877-8879, Vol. 5, nr 3, s. 208-Artikel i tidskrift (Refereegranskat)
  • 15.
    Fransén, Erik
    et al.
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Alonso, A. A.
    Dickson, C. T.
    Magistretti, J.
    Hasselmo, M. E.
    Ionic mechanisms in the generation of subthreshold oscillations and action potential clustering in entorhinal layer II stellate neurons2004Ingår i: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 14, nr 3, s. 368-384Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A multi compartmental biophysical model of entorhinal cortex layer II stellate cells was developed to analyze the ionic basis of physiological properties, such as subthreshold membrane potential oscillations, action potential clustering, and the medium afterhyperpolarization. In particular, the simulation illustrates the interaction of the persistent sodium current (I-NaP) and the hyperpolarization activated inward current (I-h) in the generation of subthreshold membrane potential oscillations. The potential role of I-h in contributing to the medium hyperpolarization (mAHP) and rebound spiking was studied. The role of I-h and the slow calcium-activated potassium current I-K(AHP) in action potential clustering was also studied. Representations of I-h and I-NaP were developed with parameters based on voltage-clamp data from whole-cell patch and single channel recordings of stellate cells (Dickson et A, J Neurophysiol 83:2562-2579, 2000; Magistretti and Alonso, J Gen Physiol 114:491-509, 1999; Magistretti et al., J Physiol 521:629-636, 1999a; J Neurosci 19:7334-7341, 1999b). These currents interacted to generate robust subthreshold membrane potentials with amplitude and frequency corresponding to data observed in the whole cell patch recordings. The model was also able to account for effects of pharmacological manipulations, including blockade of I-h with ZD7288, partial blockade with cesium, and the influence of barium on oscillations. In a model with a wider range of currents, the transition from oscillations to single spiking, to spike clustering, and finally tonic firing could be replicated. In agreement with experiment, blockade of calcium channels in the model strongly reduced clustering. In the voltage interval during which no data are available, the model predicts that the slow component of I-h does not follow the fast component down to very short time constants. The model also predicts that the fast component of I-h is responsible for the involvement in the generation of subthreshold oscillations, and the slow component dominates in the generation of spike clusters.

  • 16.
    Fransén, Erik
    et al.
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Alonso, A. A.
    Hasselmo, M. E.
    Entorhinal neuronal activity during delayed matching tasks may depend upon muscarinic-induced non-specific cation current I(CANM)2001Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 38, s. 601-606Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Biophysical compartmental models of stellate, pyramidal-like and interneurons in layer II of the rat entorhinal cortex were used to explore cellular and synaptic components involved in neuronal responses to stimuli in a delayed match to sample (DMS) task. Simulations demonstrate that the muscarinic receptor-induced non-specific cation current, I(CANM), could contribute to these phenomena. Facilitation of I(CANM) by calcium influx during spikes induced by the sample stimulus can cause enhanced responses for matches as well as delay activity. In a network, lateral inhibition can produce match suppression, and in conjunction with stimulus selective/non-selective cells produce non-match enhancement and suppression.

  • 17.
    Fransén, Erik
    et al.
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Alonso, A. A.
    Hasselmo, M. E.
    Simulations of the role of the muscarinic-activated calcium-sensitive nonspecific cation current I-NCM in entorhinal neuronal activity during delayed matching tasks2002Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 22, nr 3, s. 1081-1097Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Entorhinal lesions impair performance in delayed matching tasks, and blockade of muscarinic cholinergic receptors also impairs performance in these tasks. Physiological data demonstrate that muscarinic cholinergic receptor stimulation activates intrinsic cellular currents in entorhinal neurons that could underlie the role of entorhinal cortex in performance of these tasks. Here we use a network biophysical simulation of the entorhinal cortex to demonstrate the potential role of this cellular mechanism in the behavioral tasks. Simulations demonstrate how the muscarinic-activated calcium-sensitive nonspecific cation current I-NCM could provide a cellular mechanism for features of the neuronal activity observed during performance of delayed matching tasks. In particular, I-NCM could underlie (1) the maintenance of sustained spiking activity during the delay period, (2) the enhancement of spiking activity during the matching period relative to the sample period, and (3) the resistance of sustained activity to distractors. Simulation of a larger entorhinal network with connectivity chosen randomly within constraints on number, distribution, and weight demonstrates appearance of other phenomena observed in unit recordings from awake animals, including match suppression, non-match enhancement, and non-match suppression.

  • 18.
    Fransén, Erik
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Kozlov, Alexander
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Xie, Yuecong
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Christensen, C.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Djurfeldt, Mikael
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Ekeberg, Örjan
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Evaluation of model scalability in parallel neural simulators2005Konferensbidrag (Refereegranskat)
    Abstract [en]

    A long standing belief in neuroscience has been that the brain and specifically the neocortex obtains its computational power by massive parallelism. Albeit conceptually appealing, this notion that effective processing requires large networks has not been possible to test in detailed simulations. In one project, we intend to study the generation of theta activity in the entorhinal-hippocampal system. Several simulation studies indicate that frequency and synchronization of the oscillation generated may depend on density of connectivity and/or geometry of connections. In a second project, we are studying how a model of early visual processing scales towards realistic sizes. To effectively evaluate the model, it must be scaled up to sizes where processing demands from the input given are sufficiently high, and where network size is made sufficiently large to process this information.

    We have in preliminary studies tested two parallel simulators. One is a version of pGENESIS supporting MPI from University of Sunderland, UK. The other is Split, a software produced in our own laboratory. Both have been tested on an Itanium2 cluster. Tests include variable number of processors and scaling number of neurons/compartments or number of synapses. In these simulations, average spike frequency in the network is also varied. The aim is to identify main bottle-necks. For instance, we foresee the need to parallelize the construction/layout of synapses.

  • 19.
    Fransén, Erik
    et al.
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Lansner, Anders
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    A model of cortical associative memory based on a horizontal network of connected columns1998Ingår i: Network, ISSN 0954-898X, E-ISSN 1361-6536, Vol. 9, nr 2, s. 235-264Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    An attractor network model of cortical associative memory functions has been constructed and simulated. By replacing the single cell as the functional unit by multiple cells in cortical columns connected by long-range fibers, the model is improved in terms of correspondence with cortical connectivity. The connectivity is improved, since the original dense and symmetric connectivity of a standard recurrent network becomes sparse and asymmetric at the cell-to-cell level. Our simulations show that this kind of network, with model neurons of the Hodgkin-Huxley type arranged in columns, can operate as an associative memory in much the same way as previous models having simpler connectivity. The network shows attractor-like behaviour and performs the standard assembly operations despite differences in the dynamics introduced by the more detailed cell model and network structure. Furthermore, the model has become sufficiently detailed to allow evaluation against electrophysiological and anatomical observations. For instance, cell activities comply with experimental findings and reaction times are within biological and psychological ranges. By introducing a scaling model we demonstrate that a network approaching experimentally reported neuron numbers and synaptic distributions also could work like the model studied here.

  • 20.
    Fransén, Erik
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Petersson, Marcus E.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Tigerholm, Jenny
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Andersson, Sten
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Obreja, O
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Lampert, A
    Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
    Carr, R
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Schmelz, M
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Differences in action potential propagation in mechanosensitive and insensitive C-nociceptors - a modeling approach2012Konferensbidrag (Refereegranskat)
    Abstract [en]

    C-fibers, unmyelinated afferent axons, convey information from the periphery of the nervous system to the spinal cord. They transmit signals originating from noxious stimulation evoking the sensations of itch and pain in the central nervous system. Different classes of C-fibers are characterized by functional, morphological and biochemical characteristics. In pain studies, a classification into mechano-insensitive (CMi) and mechano responsive fibers (CM) has proven useful as changes in proportions and response characteristics of these fibers have been observed in neuropathy patients (Weidner et al. 1999, 2000; Orstavik 2003, 2010). In this study, using computational modeling of a C-fiber, we have studied the possible contribution of different ion channel subtypes (Na-TTXs, Nav1.8, Nav1.9, Kdr, KA, KM, K(Na), h) as well as the Na/K-ATPase pump to conductive properties of C-fibers. In particular we investigated mechanisms that could generate the fiber-specific differences between CM and CMi fibers with regard to activity dependent slowing (ADS) and recovery cycles (RC). In our study we represent the axon by three cylindrical sections, one representing the peripheral thin end (branch, 2.5 cm), one the central part (parent, 10 cm) and a conical section between these (0.5 cm). In total 730 compartments are used. Temperature is set to 32 degrees C in branch and 37 degrees in parent sections. We represent variable ion concentrations of Na and K intra axonally, periaxonally and extracellularly, from which reversal potentials are calculated. We use ion channel models based on Hodgkin Huxley formalism. An ion pump (Na/K-ATPase) is included. We find that TTX-sensitive Na and Nav1.8 have the strongest influence on action potential conduction velocity as is expected since these are the major components of the rising phase of the action potential. Preliminary observations indicate that a small subset of Na and K currents play a key role in determining differences in activity dependent velocity changes (ADS) in the two fiber classes. We plan to also study contributions from morphological characteristics (superficial branch lengths) to activity dependent differences between the fiber classes (Schmidt et al. 2002). We further intend to investigate candidate ion channels which could play a role in changing the functional characteristics of a CMi fiber to that of a CM fiber. Our studies may provide insights into ionic changes underlying changes in the excitability of C-fibers associated with pain.

  • 21.
    Fransén, Erik
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Tahvildari, B.
    Egorov, A. V.
    Hasselmo, M. E.
    Alonso, A. A.
    Mechanism of graded persistent cellular activity of entorhinal cortex layer V neurons2006Ingår i: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 49, nr 5, s. 735-746Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Working memory is an emergent property of neuronal networks, but its cellular basis remains elusive. Recent data show that principal neurons of the entorhinal cortex display persistent firing at graded firing rates that can be shifted up or down in response to brief excitatory or inhibitory stimuli. Here, we present a model of a potential mechanism for graded firing. Our multicompartmental model provides stable plateau firing generated by a nonspecific calcium-sensitive cationic (CAN) current. Sustained firing is insensitive to small variations in Ca2+ concentration in a neutral zone. However, both high and low Ca2+ levels alter firing rates. Specifically, increases in persistent firing rate are triggered only during high levels of calcium, while decreases in rate occur in the presence of low levels of calcium. The model is consistent with detailed experimental observations and provides a mechanism for maintenance of memory-related activity in individual neurons.

  • 22.
    Fransén, Erik
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Tigerholm, Jenny
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Role of A-type potassium currents in excitability, network synchronicity, and epilepsy2010Ingår i: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 20, nr 7, s. 877-887Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A range of ionic currents have been suggested to be involved in distinct aspects of epileptogenesis. Based on pharmacological and genetic studies, potassium currents have been implicated, in particular the transient A-type potassium current (K-A). Epileptogenic activity comprises a rich repertoire of characteristics, one of which is synchronized activity of principal cells as revealed by occurrences of for instance fast ripples. Synchronized activity of this kind is particularly efficient in driving target cells into spiking. In the recipient cell, this synchronized input generates large brief compound excitatory postsynaptic potentials (EPSPs). The fast activation and inactivation of K-A lead us to hypothesize a potential role in suppression of such EPSPs. In this work, using computational modeling, we have studied the activation of K-A by synaptic inputs of different levels of synchronicity. We find that K-A participates particularly in suppressing inputs of high synchronicity. We also show that the selective suppression stems from the current's ability to become activated by potentials with high slopes. We further show that K-A suppresses input mimicking the activity of a fast ripple. Finally, we show that the degree of selectivity of K-A can be modified by changes to its kinetic parameters, changes of the type that are produced by the modulatory action of KChIPs and DPPs. We suggest that the wealth of modulators affecting K-A might be explained by a need to control cellular excitability in general and suppression of responses to synchronicity in particular. We also suggest that compounds changing K-A-kinetics may be used to pharmacologically improve epileptic status.

  • 23.
    Fransén, Erik
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Tigerholm, Jenny
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Petersson, Marcus E.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Carr, R
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, German.
    Obreja, O
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Lampert, A
    Institute of Physiology and Pathophysiology, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany.
    Schmelz, M
    Dept. of Anaesthesiology Mannheim, Heidelberg University, Mannheim, Germany.
    Computational modeling of activity dependent velocity changes in peripheral C-fibers2011Konferensbidrag (Refereegranskat)
    Abstract [en]

    Initiation and propagation of action potentials along unmyelinated C-fibers are the first steps of the pain pathway. Propagation velocity and its fiber class-specific activity-dependent slowing (ADS) is intimately linked to fibre excitability. In chronic pain patients, ADS alterations have been suggested to reflect increased excitability, possibly underlying clinical pain. Due to their small diameter, peripheral axons of nociceptors in patients are not accessible for intraaxonal recordings of their ion channel properties. We have therefore constructed a model of a C-fibre to study the relationship between ion channel composition and velocity changes as well as excitability. Ion channels are modeled from data of DRG somata using a Hodgkin-Huxley formalism (Na currents: TTX-sensitive, Nav1.8, Nav1.9, K currents: Kdr, A-type, Kv7.3, non-specific cationic: HCN). Moreover, ion pumps (Na/K-ATPase) and concentrations of intra and extraaxonal sodium and potassium are also included. The geometry and temperature of the fibre represents a section of the superficial branch and the deeper parent and is represented by a multicompartmental structure where each compartment contains passive as well as ion channel and pump elements. Using parameter estimation techniques, we optimized ion channel and pump expression pattern such that basic electrophysiological characteristics of the action potential and its velocity matched the experimental data. Moreover, we have also replicated activity dependent slowing. In ongoing work, we extend optimization to also include recovery cycles. The model will be used to study hypothesis of the relationship between individual ion channel subtypes and axonal excitability related to pain, generating independent information on impact of selective neuronal targets.

  • 24. Giocomo, Lisa M.
    et al.
    Zilli, Eric A.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hasselmo, Michael E.
    Temporal frequency of subthreshold oscillations scales with entorhinal grid cell field spacing2007Ingår i: Science, ISSN 0036-8075, E-ISSN 1095-9203, Vol. 315, nr 5819, s. 1719-1722Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Grid cells in layer II of rat entorhinal cortex fire to spatial locations in a repeating hexagonal grid, with smaller spacing between grid fields for neurons in more dorsal anatomical locations. Data from in vitro whole-cell patch recordings showed differences in frequency of subthreshold membrane potential oscillations in entorhinal neurons that correspond to different positions along the dorsal-to-ventral axis, supporting a model of physiological mechanisms for grid cell responses.

  • 25. Hasselmo, M. E.
    et al.
    Fransén, Erik
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Dickson, C.
    Alonso, A. A.
    Computational modeling of entorhinal cortex2000Ingår i: PARAHIPPOCAMPAL REGION: IMPLICATIONS FOR NEUROLOGICAL AND PSYCHIATRIC DISEASES / [ed] Scharfman, HE; Witter, MP; Schwarcz, R, NEW YORK: New York Academy of Sciences, 2000, Vol. 911, s. 418-446Konferensbidrag (Refereegranskat)
    Abstract [en]

    Computational modeling provides a means for linking the physiological and anatomical characteristics of entorhinal cortex at a cellular level to the functional role of this region in behavior. We have developed detailed simulations of entorhinal cortical neurons and networks, with an emphasis on the role of acetylcholine in entorhinal cortical function. Computational modeling suggests that when acetylcholine levels are high, this sets appropriate dynamics for the storage of stimuli during performance of delayed matching tasks. In particular, acetylcholine activates a calcium-sensitive nonspecific cation current which provides an intrinsic cellular mechanism which could maintain neuronal activity across a delay period. Simulations demonstrate how this phenomena could underlie entorhinal cortex delay activity as described in previous unit recordings. Acetylcholine also induces theta rhythm oscillations which may be appropriate for timing of afferent input to be encoded in hippocampus and for extraction of individual stored sequences from multiple stored sequences. Lower levels of acetylcholine may allow sharp wave dynamics which can reactivate associations encoded in hippocampus and drive the formation of additional traces in hippocampus and entorhinal cortex during consolidation.

  • 26. Hasselmo, Michael E.
    et al.
    Brandon, Mark P.
    Yoshida, Motoharu
    Giocomo, Lisa M.
    Heys, James G.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Newman, Ehren L.
    Zilli, Eric A.
    A phase code for memory could arise from circuit mechanisms in entorhinal cortex2009Ingår i: Neural Networks, ISSN 0893-6080, E-ISSN 1879-2782, Vol. 22, nr 8, s. 1129-1138Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neurophysiological data reveals intrinsic cellular properties that suggest how entorhinal cortical neurons could code memory by the phase of their firing. Potential cellular mechanisms for this phase coding in models of entorhinal function are reviewed. This mechanism for phase coding provides a substrate for modeling the responses of entorhinal grid cells, as well as the replay of neural spiking activity during waking and sleep. Efforts to implement these abstract models in more detailed biophysical compartmental simulations raise specific issues that could be addressed in larger scale population models incorporating mechanisms of inhibition.

  • 27.
    Lansner, Anders
    et al.
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Fransén, Erik
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Sandberg, Anders
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Cell assembly dynamics in detailed and abstract attractor models of cortical associative memory2003Ingår i: Theory in biosciences, ISSN 1431-7613, E-ISSN 1611-7530, Vol. 122, nr 1, s. 19-36Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    During the last few decades we have seen a convergence among ideas and hypotheses regarding functional principles underlying human memory. Hebb's now more than fifty years old conjecture concerning synaptic plasticity and cell assemblies, formalized mathematically as attractor neural networks, has remained among the most viable and productive theoretical frameworks. It suggests plausible explanations for Gestalt aspects of active memory like perceptual completion, reconstruction and rivalry. We review the biological plausibility of these theories and discuss some critical issues concerning their associative memory functionality in the light of simulation studies of models with palimpsest memory properties. The focus is on memory properties and dynamics of networks modularized in terms of cortical minicolumns and hypercolumns. Biophysical compartmental models demonstrate attractor dynamics that support cell assembly operations with fast convergence and low firing rates. Using a scaling model we obtain reasonable relative connection densities and amplitudes. An abstract attractor network model reproduces systems level psychological phenomena seen in human memory experiments as the Sternberg and von Restorff effects. We conclude that there is today considerable substance in Hebb's theory of cell assemblies and its attractor network formulations, and that they have contributed to increasing our understanding of cortical associative memory function. The criticism raised with regard to biological and psychological plausibility as well as low storage capacity, slow retrieval etc has largely been disproved. Rather, this paradigm has gained further support from new experimental data as well as computational modeling.

  • 28.
    Llorens, Vicente Charcos
    et al.
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Fransén, Erik
    KTH, Tidigare Institutioner, Numerisk analys och datalogi, NADA.
    Intrinsic desynchronization properties of neurons containing dendritic rapidly activating K-currents2004Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 58, s. 137-143Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In this work, we investigate the role of the potassium A-current (K-A) in linking network synchrony to cellular excitability and firing frequency. We present an analysis of the notion of synchrony and we describe its conceptual and modeling implications. An full synchronization, K-A enables a control over the timing, or even a suppression, of spikes. For completely desynchronized activity, we show how K-A affects fast changes in amplitude of the summed EPSPs as well as amount of depolarization caused by the input. Simulations at intermediate levels of synchrony suggest that activity resulting from the interaction between cellular excitability and network synchrony could be altered through K-A modulation.

  • 29.
    Petersson, Marcus E.
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Role of TRP channels in dendritic integration and subthreshold membrane potential plateaus2011Ingår i: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 12, nr Suppl 1, s. P110-Artikel i tidskrift (Övrigt vetenskapligt)
  • 30.
    Petersson, Marcus E.
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Stable subthreshold dendritic membrane potential plateaus maintained by TRP currents2011Konferensbidrag (Refereegranskat)
  • 31.
    Petersson, Marcus E.
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    TRPC channels activated by group 1 mG1uR in Entorhinal pyramidal neurons support integration of low frequency (<10 Hz) synaptic inputs2009Ingår i: BMC Neuroscience, ISSN 1471-2202, Vol. 10, nr Suppl 1, s. P26-Artikel i tidskrift (Refereegranskat)
  • 32.
    Petersson, Marcus E.
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm Brain Institute, Stockholm, Sweden.
    Obreja, Otilia
    Lampert, Angelika
    Carr, Richard W.
    Schmelz, Martin
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm Brain Institute, Stockholm, Sweden.
    Differential Axonal Conduction Patterns of Mechano-Sensitive and Mechano-Insensitive Nociceptors - A Combined Experimental and Modelling Study2014Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, nr 8, s. e103556-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Cutaneous pain sensations are mediated largely by C-nociceptors consisting of both mechano-sensitive (CM) and mechano-insensitive (CMi) fibres that can be distinguished from one another according to their characteristic axonal properties. In healthy skin and relative to CMi fibres, CM fibres show a higher initial conduction velocity, less activity-dependent conduction velocity slowing, and less prominent post-spike supernormality. However, after sensitization with nerve growth factor, the electrical signature of CMi fibres changes towards a profile similar to that of CM fibres. Here we take a combined experimental and modelling approach to examine the molecular basis of such alterations to the excitation thresholds. Changes in electrical activation thresholds and activity-dependent slowing were examined in vivo using single-fibre recordings of CM and CMi fibres in domestic pigs following NGF application. Using computational modelling, we investigated which axonal mechanisms contribute most to the electrophysiological differences between the fibre classes. Simulations of axonal conduction suggest that the differences between CMi and CM fibres are strongly influenced by the densities of the delayed rectifier potassium channel (Kdr), the voltage-gated sodium channels Na(V)1.7 and Na(V)1.8, and the Na+/K+-ATPase. Specifically, the CM fibre profile required less K-dr and Na(V)1.8 in combination with more Na(V)1.7 and Na+/ K(+)AT-Pase. The difference between CM and CMi fibres is thus likely to reflect a relative rather than an absolute difference in protein expression. In support of this, it was possible to replicate the experimental reduction of the ADS pattern of CMi nociceptors towards a CM-like pattern following intradermal injection of nerve growth factor by decreasing the contribution of Kdr (by 50%), increasing the Na+/K+-ATPase (by 10%), and reducing the branch length from 2 cm to 1 cm. The findings highlight key molecules that potentially contribute to the NGF-induced switch in nociceptors phenotype, in particular NaV1.7 which has already been identified clinically as a principal contributor to chronic pain states such as inherited erythromelalgia.

  • 33.
    Petersson, Marcus E.
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Yoshida, Motoharu
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Low-frequency summation of synaptically activated transient receptor potential channel-mediated depolarizations2011Ingår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 34, nr 4, s. 578-593Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neurons sum their input by spatial and temporal integration. Temporally, presynaptic firing rates are converted to dendritic membrane depolarizations by postsynaptic receptors and ion channels. In several regions of the brain, including higher association areas, the majority of firing rates are low. For rates below 20 Hz, the ionotropic receptors alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor and N-methyl-d-aspartate (NMDA) receptor will not produce effective temporal summation. We hypothesized that depolarization mediated by transient receptor potential (TRP) channels activated by metabotropic glutamate receptors would be more effective, owing to their slow kinetics. On the basis of voltage-clamp and current-clamp recordings from a rat slice preparation, we constructed a computational model of the TRP channel and its intracellular activation pathway, including the metabotropic glutamate receptor. We show that synaptic input frequencies down to 3-4 Hz and inputs consisting of as few as three to five pulses can be effectively summed. We further show that the time constant of integration increases with increasing stimulation frequency and duration. We suggest that the temporal summation characteristics of TRP channels may be important at distal dendritic arbors, where spatial summation is limited by the number of concurrently active synapses. It may be particularly important in regions characterized by low and irregular rates.

  • 34.
    Petersson, Marcus
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Long-lasting small-amplitude TRP-mediated dendritic depolarizations in CA1 pyramidal neurons are intrinsically stable and originate from distal tuft regions2012Ingår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 36, nr 7, s. 2917-2925Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In several regions of the nervous system, neurons display bi- or multistable intrinsic properties. Such stable states may be subthreshold and long-lasting, and can appear as a sustained afterdepolarization. In hippocampal CA1 pyramidal neurons, small-amplitude (1 mV) long-lasting (seconds) afterdepolarizations have been reported and are thought to depend on calcium-activated nonselective (CAN) currents recently identified as transient receptor potential (TRP) channels. Continuing our previous experimental and computational work on synaptically metabotropic glutamate receptor (mGluR)-activated TRP currents, we here explore small-amplitude long-lasting depolarizations in a detailed multicompartmental model of a CA1 pyramidal neuron. We confirm a previous hypothesis suggesting that the depolarization results from an interplay of TRP and voltage-gated calcium channels, and contribute to the understanding of the depolarization in several ways. Specifically, we show that: (i) the long-lasting depolarization may be intrinsically stable to weak excitatory and inhibitory input, (ii) the phenomenon is essentially located in distal apical dendrites, (iii) induction is facilitated if simultaneous input arrives at several dendritic branches, and if calcium- and/or mGluR-evoked signals undergo summation, suggesting that both spatial and temporal synaptic summation might be required for the depolarization to occur and (iv) we also show that the integration of inputs to oblique dendrites is strongly modulated by the presence of small-amplitude long-lasting depolarizations in distal tuft dendrites. To conclude, we suggest that small-amplitude long-lasting dendritic depolarizations may contribute to sustaining neural information during behavioural tasks in cases where information is separated in time, as in trace conditioning and delay tasks.

  • 35.
    Petersson, Marcus
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Obreja, Otilia
    Lampert, Angelika
    Carr, Richard
    Schmelz, Martin
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    C-type peripheral nociceptors differ in axonal ion channel densitiesManuskript (preprint) (Övrigt vetenskapligt)
  • 36.
    Roos, Mikael
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Yamamoto, Shin-Ichiro
    Fransen, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Ekeberg, Örjan
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Tasuku, Miyoshi
    Modeling and controlling a gait training system utilizing a biarticular muscle model2006Ingår i: Japan Society of Mechanical Engineers Symposium on Welfare Engineering, Vol. 2006, s. 234-235Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In the purpose of rehabilitation for people unable to perform a normal gait pattern a pneumatically operated gait training system with a biarticular muscle model utilizing rubbertuators have been developed. The pneumatics and the biarticular characteristics make the system difficult to control. In this research paper machine learning techniques have been used in an attempt to design a control system for the pneumatic gait. Preliminary results indicate that inverse plant modeling using Artificial Neural Networks (ANN) might be a successful approach.

  • 37.
    Sandberg, Anders
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    An autocatalytic model of STDP timing from slow calcium-dependent signals2005Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 65-66, s. 603-608Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Data of spike timing-dependent plasticity (STDP) show a sharp temporal transition between potentiation and depression despite a relatively slow time course of calcium concentration. We show how autocatalytic amplification of initial concentration differences can enable a high degree of temporal selectivity and produce the sharp STDP weight change curve despite having a relatively slow time constant. This simple model is robust to parameter changes, noise and details of the model. The model correctly predicts the location of the maximum and minimum for STDP at +/- 10ms from coincidence.

  • 38.
    Smolinski, T.
    et al.
    Department of Psychology, Boston University, MA, USA.
    Patel, P.
    Department of Psychology, Boston University, MA, USA.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hasselmo, M.
    Department of Psychology, Boston University, MA, USA.
    Schultheiss, N.
    Department of Psychology, Boston University, MA, USA.
    A computational intelligence approach to evaluation of membrane conductance interactions underlying persistent spiking, the f-I curve, and adaptive properties of medial entorhinal cortex neurons2012Konferensbidrag (Refereegranskat)
  • 39. Tahvildari, Babak
    et al.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Alonso, Angel A.
    Hasselmo, Michael E.
    Switching between on and off states of persistent activity in lateral entorhinal layer III neurons2007Ingår i: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 17, nr 4, s. 257-263Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Persistent neural spiking maintains information during a, working memory task when a stimulus is no longer present. During I retention, this activity needs to be stable to distractors. More importantly, when retention is no longer relevant, cessation of the activity is necessary to enable processing and retention of subsequent information. Here, by means of intracellular recording with sharp microelectrode in in vitro rat brain slices, we demonstrate that single principal layer III neurons of the lateral entorhinal cortex (EC) generate persistent spiking activity with a novel ability to reliably toggle between spiking activity and a silent state. Our data indicates that in the presence of muscarmic receptor activation, persistent activity following an excitatory input may be induced and that a subsequent excitatory input can terminate this activity and cause the neuron to return to a silent state. Moreover, application of inhibitory hyperpolarizing stimuli is neither able to decrease the frequency of the persistent activity nor terminate it. The persistent activity can also be initiated and terminated by synchronized synaptic stimuli of layer II/III of the perirhinal cortex. The neuronal ability to switch On and Off persistent activity may facilitate the concurrent representation of temporally segregated information arriving in the EC and being directed toward the hippocampus.

  • 40.
    Tigerholm, Jenny
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Börjesson, Sara
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University.
    Lundberg, Linnea
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Elinder, Fredrik
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Dampening of Hyperexcitability in CA1 Pyramidal Neurons by Polyunsaturated Fatty Acids Acting on Voltage-Gated Ion Channels2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 9, s. e44388-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    A ketogenic diet is an alternative treatment of epilepsy in infants. The diet, rich in fat and low in carbohydrates, elevates the level of polyunsaturated fatty acids (PUFAs) in plasma. These substances have therefore been suggested to contribute to the anticonvulsive effect of the diet. PUFAs modulate the properties of a range of ion channels, including K and Na channels, and it has been hypothesized that these changes may be part of a mechanistic explanation of the ketogenic diet. Using computational modelling, we here study how experimentally observed PUFA-induced changes of ion channel activity affect neuronal excitability in CA1, in particular responses to synaptic input of high synchronicity. The PUFA effects were studied in two pathological models of cellular hyperexcitability associated with epileptogenesis. We found that experimentally derived PUFA modulation of the A-type K (K-A) channel, but not the delayed-rectifier K channel, restored healthy excitability by selectively reducing the response to inputs of high synchronicity. We also found that PUFA modulation of the transient Na channel was effective in this respect if the channel's steady-state inactivation was selectively affected. Furthermore, PUFA-induced hyperpolarization of the resting membrane potential was an effective approach to prevent hyperexcitability. When the combined effect of PUFA on the K-A channel, the Na channel, and the resting membrane potential, was simulated, a lower concentration of PUFA was needed to restore healthy excitability. We therefore propose that one explanation of the beneficial effect of PUFAs lies in its simultaneous action on a range of ion-channel targets. Furthermore, this work suggests that a pharmacological cocktail acting on the voltage dependence of the Na-channel inactivation, the voltage dependences of K-A channels, and the resting potential can be an effective treatment of epilepsy.

  • 41.
    Tigerholm, Jenny
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    KA channels reduce dendritic depolarization from synchronized synaptic input: implication for neural processing and epilepsy2008Ingår i: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 9, nr Suppl 1, s. P45-Artikel i tidskrift (Refereegranskat)
  • 42.
    Tigerholm, Jenny
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    KA channels suppress cellular responses to fast ripple activity – implications for epilepsy2009Ingår i: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 10, nr Suppl 1, s. P226-Artikel i tidskrift (Refereegranskat)
  • 43.
    Tigerholm, Jenny
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Restoring ion channel pathology by parameter optimization2011Ingår i: BMC neuroscience (Online), ISSN 1471-2202, E-ISSN 1471-2202, Vol. 12, nr Suppl 1, s. P334-Artikel i tidskrift (Refereegranskat)
  • 44.
    Tigerholm, Jenny
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Reversing Nerve Cell Pathology by Optimizing Modulatory Action on Target Ion Channels2011Ingår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 101, nr 8, s. 1871-1879Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In diseases of the brain, the distribution and properties of ion channels display deviations from healthy control subjects. We studied three cases of ion channel alteration related to epileptogenesis. The first case of ion channel alteration represents an enhanced sodium current, the second case addresses the downregulation of the transient potassium current K(A), and the third case relates to kinetic properties of K(A) in a patient with temporal lobe epilepsy. Using computational modeling and optimization, we aimed at reversing the pathological characteristics and restoring normal neural function by altering ion channel properties. We identified two key aspects of neural dysfunction in epileptogenesis: an enhanced response to synaptic input in general and to highly synchronized synaptic input in particular. In previous studies, we showed that the potassium channel K(A) played a major role in neural responses to highly synchronized input. It was therefore selected as the target upon which modulators would act. In biophysical simulations, five experimentally characterized endogenous modulations on the K(A) channel were included. Relative concentrations of these modulators were controlled by a numerical optimizer that compared model output to predefined neural output, which represented a normal physiological response. Several solutions that restored the neuron function were found. In particular, distinct subtype compositions of the auxiliary proteins Kv channel-interacting proteins 1 and dipeptidyl aminopeptidase-like protein 6 were able to restore changes imposed by the enhanced sodium conductance or suppressed K(A) conductance. Moreover, particular combinations of protein kinese C, calmodulin-dependent protein kinase II, and arachidonic acid were also able to restore these changes as well as the channel pathology found in a patient with temporal lobe epilepsy. The solutions were further analyzed for sensitivity and robustness. We suggest that the optimization procedure can be used not only for neurons, but also for other organs with excitable cells, such as the heart and pancreas where channelopathies are found.

  • 45.
    Tigerholm, Jenny
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Migliore, Michele
    Institute of Biophysics, National Research Council.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Integration of synchronous synaptic input in CA1 pyramidal neuron depends on spatial and temporal distributions of the input2013Ingår i: Hippocampus, ISSN 1050-9631, E-ISSN 1098-1063, Vol. 23, nr 1, s. 87-99Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Highly synchronized neural firing has been discussed in relation to learning and memory, for instance sharp-wave activity in hippocampus. We were interested to study how a postsynaptic CA1 pyramidal neuron would integrate input of different levels of synchronicity. In previous work using computational modeling we studied how the integration depends on dendritic conductances. We found that the transient A-type potassium channel KA was able to selectively suppress input of high synchronicity. In recent years, compartmentalization of dendritic integration has been shown. We were therefore interested to study the influence of localization and pattern of synaptic input over the dendritic tree of the CA1 pyramidal neuron. We find that the selective suppression increases when synaptic inputs are placed on oblique dendrites further out from the soma. The suppression also increases along the radial axis from the apical trunk out to the end of oblique dendrites. We also find that the KA channel suppresses the occurrence of dendritic spikes. Moreover, recent studies have shown interaction between synaptic inputs. We therefore studied the influence of apical tuft input on the integration studied above. We find that excitatory input provides a modulatory influence reducing the capacity of KA to suppress synchronized activity, thus facilitating the excitatory drive of oblique dendritic input. Conversely, inhibitory tuft input increases the suppression by KA providing a larger control of oblique depolarizing factors on the CA1 pyramidal neuron in terms of what constitutes the most effective level of synchronicity. Furthermore, we show that the selective suppression studied above depends on the conductance of the KA channel. KA, as several other potassium channels, is modulated by several neuromodulators, for instance acetylcholine and dopamine, both of which have been discussed in relation to learning and memory. We suggest that dendritic conductances and their modulatory systems may be part of the regulation of processing of information, in particular for how network synchronicity affects learning and memory.

  • 46.
    Tigerholm, Jenny
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm Brain Institute, Sweden.
    Petersson, Marcus E.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm Brain Institute, Sweden.
    Obreja, Otilia
    Eberhardt, Esther
    Namer, Barbara
    Weidner, Christian
    Lampert, Angelika
    Carr, Richard
    Schmelz, Martin
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm Brain Institute, Sweden.
    C-Fiber Recovery Cycle Supernormality Depends on Ion Concentration and Ion Channel Permeability2015Ingår i: Biophysical Journal, ISSN 0006-3495, E-ISSN 1542-0086, Vol. 108, nr 5, s. 1057-1071Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Following each action potential, C-fiber nociceptors undergo cyclical changes in excitability, including a period of superexcitability, before recovering their basal excitability state. The increase in superexcitability during this recovery cycle depends upon their immediate firing history of the axon, but also determines the instantaneous firing frequency that encodes pain intensity. To explore the mechanistic underpinnings of the recovery cycle phenomenon a biophysical model of a C-fiber has been developed. The model represents the spatial extent of the axon including its passive properties as well as ion channels and the Na/K-ATPase ion pump. Ionic concentrations were represented inside and outside the membrane. The model was able to replicate the typical transitions in excitability from subnormal to supernormal observed empirically following a conducted action potential. In the model, supernormality depended on the degree of conduction slowing which in turn depends upon the frequency of stimulation, in accordance with experimental findings. In particular, we show that activity-dependent conduction slowing is produced by the accumulation of intraaxonal sodium. We further show that the supernormal phase results from a reduced potassium current K-dr as a result of accumulation of periaxonal potassium in concert with a reduced influx of sodium through Na(v)1.7 relative to Na(v)1.8 current. This theoretical prediction was supported by data from an in vitro preparation of small rat dorsal root ganglion somata showing a reduction in the magnitude of tetrodotoxin-sensitive relative to tetrodotoxin - resistant whole cell current. Furthermore, our studies provide support for the role of depolarization in supernormality, as previously suggested, but we suggest that the basic mechanism depends on changes in ionic concentrations inside and outside the axon. The understanding of the mechanisms underlying repetitive discharges in recovery cycles may provide insight into mechanisms of spontaneous activity, which recently has been shown to correlate to a perceived level of pain.

  • 47.
    Tigerholm, Jenny
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm Brain Institute, Stockholm, Sweden.
    Petersson, Marcus
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm Brain Institute, Stockholm, Sweden.
    Obreja, Otilia
    Anaesthesiology, Universitaetsmedizin Mannheim, Univ. of Heidelberg.
    Lampert, Angelika
    Inst. of Physiol. and Pathophysiology, Friedrich-Alexander-Uni versität Erlangen-Nürnberg.
    Carr, Richard
    Anaesthesiology, Universitaetsmedizin Mannheim, Univ. of Heidelberg.
    Schmelz, Martin
    Anaesthesiology, Universitaetsmedizin Mannheim, Univ. of Heidelberg,.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm Brain Institute, Stockholm, Sweden.
    Modeling activity-dependent changes of axonal spike conduction in primary afferent C-nociceptors2014Ingår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 111, nr 9, s. 1721-1735Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Action potential initiation and conduction along peripheral axons is a dynamic process that displays pronounced activity dependence. In patients with neuropathic pain, differences in the modulation of axonal conduction velocity by activity suggest that this property may provide insight into some of the pathomechanisms. To date, direct recordings of axonal membrane potential have been hampered by the small diameter of the fibers. We have therefore adopted an alternative approach to examine the basis of activity-dependent changes in axonal conduction by constructing a comprehensive mathematical model of human cutaneous C-fibers. Our model reproduced axonal spike propagation at a velocity of 0.69 m/s commensurate with recordings from human C-nociceptors. Activity-dependent slowing (ADS) of axonal propagation velocity was adequately simulated by the model. Interestingly, the property most readily associated with ADS was an increase in the concentration of intra-axonal sodium. This affected the driving potential of sodium currents, thereby producing latency changes comparable to those observed for experimental ADS. The model also adequately reproduced post-action potential excitability changes (i.e., recovery cycles) observed in vivo. We performed a series of control experiments replicating blockade of particular ion channels as well as changing temperature and extracellular ion concentrations. In the absence of direct experimental approaches, the model allows specific hypotheses to be formulated regarding the mechanisms underlying activity-dependent changes in C-fiber conduction. Because ADS might functionally act as a negative feedback to limit trains of nociceptor activity, we envisage that identifying its mechanisms may also direct efforts aimed at alleviating neuronal hyperexcitability in pain patients.

  • 48.
    Tigerholm, Jenny
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Petersson, Marcus
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Obreja, Otilia
    Lampert, Angelika
    Carr, Richard
    Schmelz, Martin
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Modelling post spike excitability changes in peripheral C-fibres2012Manuskript (preprint) (Övrigt vetenskapligt)
  • 49. Yoshida, Motoharu
    et al.
    Fransén, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hasselmo, Michael E.
    mGluR-dependent persistent firing in entorhinal cortex layer III neurons2008Ingår i: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 28, nr 6, s. 1116-1126Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Persistent firing is believed to be a crucial mechanism for memory function including working memory. Recent in vivo and in vitro findings suggest an involvement of metabotropic glutamate receptors (mGluRs) in persistent firing. Using whole-cell patch-recording techniques in a rat entorhinal cortex (EC) slice preparation, we tested whether EC layer III neurons display persistent firing due to mGluR activation, independently of cholinergic activation. Stimulation of the angular bundle drove persistent firing in 90% of the cells in the absence of a cholinergic agonist. The persistent firing was typically stable for > 4.5 min at which point persistent firing was terminated by the experimenter. The average frequency of the persistent firing was 2.1 Hz, ranging from 0.4 to 5.5 Hz. This persistent firing was observed even in the presence of atropine (2 mu M), suggesting that the persistent firing can occur independent of cholinergic activation. Furthermore, ionotropic glutamate and GABAergic synaptic blockers (2 mm kynurenic acid, 100 mu M picrotoxin and 1 mu M CGP55845) did not block the persistent firing. On the other hand, blockers of group I mGluRs (100 mu M LY367385 and 20 mu M MPEP) completely blocked or suppressed the persistent firing. An agonist of group I mGluRs (20 mu M DHPG) greatly enhanced the persistent firing induced by current injection. These results indicate that persistent firing can be driven through group I mGluRs in entorhinal layer III neurons, suggesting that glutamatergic synaptic input alone could enable postsynaptic neurons to hold input signals in the form of persistent firing.

  • 50.
    Zhu, Fei
    et al.
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland.;UCL Inst Neurol, Queen Sq, London WC1N 3BG, England..
    Cizeron, Melissa
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland.;Univ Claude Bernard Lyon 1, Univ Lyon, Inst NeuroMyoGene, CNRS,UMR 5310,INSERM,U1217, F-69008 Lyon, France..
    Qiu, Zhen
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland..
    Benavides-Piccione, Ruth
    CSIC, Inst Cajal, E-28002 Madrid, Spain.;UPM, Ctr Tecnol Biomed, Madrid 28223, Spain.;ISCIII, CIBERNED, Madrid 28031, Spain..
    Kopanitsa, Maksym V.
    Synome Ltd, Babraham Res Campus, Cambridge CB22 3AT, England.;Imperial Coll London, UK Dementia Res Inst, London W12 0NN, England..
    Skene, Nathan G.
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland.;UCL Inst Neurol, Queen Sq, London WC1N 3BG, England.;Karolinska Inst, Dept Med Biochem & Biophys, Lab Mol Neurobiol, S-17177 Stockholm, Sweden..
    Koniaris, Babis
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland..
    DeFelipe, Javier
    CSIC, Inst Cajal, E-28002 Madrid, Spain.;UPM, Ctr Tecnol Biomed, Madrid 28223, Spain.;ISCIII, CIBERNED, Madrid 28031, Spain..
    Fransén, Erik
    KTH, Skolan för elektroteknik och datavetenskap (EECS), Beräkningsvetenskap och beräkningsteknik (CST).
    Komiyama, Noboru H.
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland..
    Grant, Seth G. N.
    Univ Edinburgh, Genes Cognit Program, Ctr Clin Brain Sci, Edinburgh EH16 4SB, Midlothian, Scotland..
    Architecture of the Mouse Brain Synaptome2018Ingår i: Neuron, ISSN 0896-6273, E-ISSN 1097-4199, Vol. 99, nr 4, s. 781-+Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Synapses are found in vast numbers in the brain and contain complex proteomes. We developed genetic labeling and imaging methods to examine synaptic proteins in individual excitatory synapses across all regions of the mouse brain. Synapse catalogs were generated from the molecular and morphological features of a billion synapses. Each synapse subtype showed a unique anatomical distribution, and each brain region showed a distinct signature of synapse subtypes. Whole-brain synaptome cartography revealed spatial architecture from dendritic to global systems levels and previously unknown anatomical features. Synaptome mapping of circuits showed correspondence between synapse diversity and structural and functional connectomes. Behaviorally relevant patterns of neuronal activity trigger spatio-temporal postsynaptic responses sensitive to the structure of synaptome maps. Areas controlling higher cognitive function contain the greatest synapse diversity, and mutations causing cognitive disorders reorganized synaptome maps. Synaptome technology and resources have wide-ranging application in studies of the normal and diseased brain.

1 - 50 av 50
RefereraExporteraLänk till träfflistan
Permanent länk
Referera
Referensformat
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Annat format
Fler format
Språk
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Annat språk
Fler språk
Utmatningsformat
  • html
  • text
  • asciidoc
  • rtf