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  • 151.
    Harischandra, Nalin
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Building a computer simulator for the study of stepping of the cat2007Rapport (Övrigt vetenskapligt)
    Abstract [en]

    We have developed a 3-dimensional computer simulator for investigation on the neuro-musculo-skeletal system and its interactions during normal walking of the cat. Main components of the cat model are the simulation of skeletal dynamics and the control system that includes a mathematical muscle model and a central pattern generator (CPG) network. The simulator is programmed in Python scripting language with other supported open source libraries such as Open Dynamics Engine (ODE) for body dynamics and Opengl for 3-D graphical representation. Modular structure and the object oriented programming technique allows easy access to the model parameters and the modules can be easily modified without altering the entire program. To test the model’s functionality, a simple experiment, during which the cat was set to walk on a flat surface with only the hind legs’ muscles were controlled by two separate CPGs with no sensory feed back, was carried out. It was possible to obtain a realistic stepping in the hind legs even without sensory feedback to the two controllers for each leg. We conclude that the mechanical linkages between the legs also play a major role in producing alternating gait.

  • 152.
    Harischandra, Nalin
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Computer Simulation of the Neural Control of Locomotion in the Cat2008Licentiatavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Locomotion is one of the most important behaviours and requires interaction between sensors at various levels of the nervous system and the limb muscles of an animal. The basic neural rhythm for locomotion in mammals has been shown to arise from local neural networks residing in the spinal cord and these networks are known as central pattern generators (CPGs). However, during the locomotion, these centres are constantly interacting with the sensory feedback signals coming from muscles, joints and peripheral skin receptors in order to adapt the stepping to varying environmental conditions. Conceptual models of mammalian locomotion have been constructed using

    mathematical models of locomotor subsystems based on the abundance of neurophysiological evidence obtained primarily in the cat. Several aspects of locomotor control using the cat as an animal model have been investigated employing computer simulations and here we use the same approach to address number of questions or/and hypotheses related to rhythmic locomotion in quadrupeds. Some of the involve questions are, role of mechanical linkage during deafferented walking, finding inherent stabilities/instabilities of muscle-joint interactions during normal walking, estimating phase dependent controlability of muscle action over joints.

    This thesis presents the basics of a biologically realistic model of mammalian locomotion and summarises methodological approaches in modelling quadruped locomotor subsystems such as CPGs, limb muscles and sensory pathways. In the first appended article, we extensively discuss the construction details of the three-dimensional computer simulator for the study of the hind leg neuro-musculo-skeletal-control system and its interactions during normal walking of the cat. The simulator with the walking model is programmed in Python scripting language with other supported open source libraries such as Open Dynamics Engine (ODE) for simulating body dynamics and OpenGL for three dimensional graphical representation. We have examined the

    functionality of the simulator and the walking model by simulating deafferented walking. It was possible to obtain a realistic stepping in the hind legs even without sensory feedback to the two controllers (CPGs) for each leg. We conclude that the mechanical linkages between the legs also play a major role in producing alternating gait.

    The use of simulations of walking in the cat for gaining insights into more complex interactions between the environment and the neuro-muscular-skeletal system is important especially for questions where a direct neurophysiological experiment can not be performed on a real walking animal. For instance, it is experimentally hard to isolate individual mechanisms without disrupting the natural walking pattern. In the second article, we introduce a different approach where we use the walking model to identify what control is necessary to maintain stability in the musculo-skeletal system. We show that the actions of most of the hindlimb muscles over the joints have an inherent stability during stepping, even without the involvement of proprioceptive feedback mechanisms. In addition, we observe that muscles generating movements in the ankle joint of the hind leg must be controlled by neural mechanisms, which may involve supraspinal structures, over the whole step cycle.

  • 153.
    Harischandra, Nalin
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Computer Simulation of the Neural Control of Locomotion in the Cat and the Salamander2011Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Locomotion is an integral part of a whole range of animal behaviours. The basic rhythm for locomotion in vertebrates has been shown to arise from local networks residing in the spinal cord and these networks are known as central pattern generators (CPG). However, during the locomotion, these centres are constantly interacting with the sensory feedback signals coming from muscles, joints and peripheral skin receptors in order to adapt the stepping or swimming to varying environmental conditions. Conceptual models of vertebrate locomotion have been constructed using mathematical models of locomotor subsystems based on the neurophysiological evidence obtained primarily in the cat and the salamander, an amphibian with a sprawling posture. Such models provide opportunity for studying the key elements in the transition from aquatic to terrestrial locomotion. Several aspects of locomotor control using the cat or the salamander as an animal model have been investigated employing computer simulations and here we use the same approach to address a number of questions or/and hypotheses related to rhythmic locomotion in quadrupeds. Some of the involved questions are, the role of mechanical linkage during deafferented walking, finding inherent stabilities/instabilities of muscle-joint interactions during normal walking and estimating phase dependent controlability of muscle action over joints. Also we investigate limb and body coordination for different gaits, use of side-stepping in front limbs for turning and the role of sensory feedback in gait generation and transitions in salamanders.

         This thesis presents the basics of the biologically realistic models of cat and salamander locomotion and summarizes computational methods in modeling quadruped locomotor subsystems such as CPG, limb muscles and sensory pathways. In the case of cat hind limb, we conclude that the mechanical linkages between the legs play a major role in producing the alternating gait. In another experiment we use the model to identify open-loop linear transfer functions between muscle activations and joint angles while ongoing locomotion. We hypothesize that the musculo-skeletal system for locomotion in animals, at least in cats, operates under critically damped condition.

         The 3D model of the salamander is successfully used to mimic locomotion on level ground and in water. We compare the walking gait with the trotting gait in simulations. We also found that for turning, the use of side-stepping alone or in combination with trunk bending is more effective than the use of trunk bending alone. The same model together with a more realistic CPG composed of spiking neurons was used to investigate the role of sensory feedback in gait generation and transition. We found that the proprioceptive sensory inputs are essential in obtaining the walking gait, whereas the trotting gait is more under central (CPG) influence compared to that of the peripheral or sensory feedback.

         This thesis work sheds light on understanding the neural control mechanisms behind vertebrate locomotion. Additionally, both neuro-mechanical models can be used for further investigations in finding new control algorithms which give robust, adaptive, efficient and realistic stepping in each leg, which would be advantageous since it can be implemented on a controller of a quadruped-robotic device.

  • 154.
    Harischandra, Nalin
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Cabelguen, Jean-Marie
    Neurocentre Magendie, Bordeaux University, Bordeaux Cedex, France.
    Ekeberg, Örjan
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    A 3D musculo-mechanical model of the salamander for the study of different gaits and modes of locomotion2010Ingår i: Frontiers in neurorobotics, ISSN 1662-5218, Vol. 4, s. 112-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Computer simulation has been used to investigate several aspects of locomotion in salamanders. Here we introduce a three-dimensional forward dynamics mechanical model of a salamander, with physically realistic weight and size parameters. Movements of the four limbs and of the trunk and tail are generated by sets of linearly modeled skeletal muscles. In this study, activation of these muscles were driven by prescribed neural output patterns. The model was successfully used to mimic locomotion on level ground and in water. We compare the walking gait where a wave of activity in the axial muscles travels between the girdles, with the trotting gait in simulations using the musculo-mechanical model. In a separate experiment, the model is used to compare different strategies for turning while stepping; either by bending the trunk or by using side-stepping in the front legs. We found that for turning, the use of side-stepping alone or in combination with trunk bending, was more effective than the use of trunk bending alone. We conclude that the musculo-mechanical model described here together with a proper neural controller is useful for neuro-physiological experiments in silico.

  • 155.
    Harischandra, Nalin
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Ekeberg, Örjan
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    System identification of muscle-joint interactions of the cat hind limb during locomotion2008Ingår i: Biological Cybernetics, ISSN 0340-1200, E-ISSN 1432-0770, Vol. 99, nr 2, s. 125-138Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Neurophysiological experiments in walking cats have shown that a number of neural control mechanisms are involved in regulating the movements of the hind legs during locomotion. It is experimentally hard to isolate individual mechanisms without disrupting the natural walking pattern and we therefore introduce a different approach where we use a model to identify what control is necessary to maintain stability in the musculo-skeletal system. We developed a computer simulation model of the cat hind legs in which the movements of each leg are produced by eight limb muscles whose activations follow a centrally generated pattern with no proprioceptive feedback. All linear transfer functions, from each muscle activation to each joint angle, were identified using the response of the joint angle to an impulse in the muscle activation at 65 postures of the leg covering the entire step cycle. We analyzed the sensitivity and stability of each muscle action on the joint angles by studying the gain and pole plots of these transfer functions. We found that the actions of most of the hindlimb muscles display inherent stability during stepping, even without the involvement of any proprioceptive feedback mechanisms, and that those musculo-skeletal systems are acting in a critically damped manner, enabling them to react quickly without unnecessary oscillations. We also found that during the late swing, the activity of the posterior biceps/semitendinosus (PB/ST) muscles causes the joints to be unstable. In addition, vastus lateralis (VL), tibialis anterior (TA) and sartorius (SAT) muscle-joint systems were found to be unstable during the late stance phase, and we conclude that those muscles require neuronal feedback to maintain stable stepping, especially during late swing and late stance phases. Moreover, we could see a clear distinction in the pole distribution (along the step cycle) for the systems related to the ankle joint from that of the other two joints, hip or knee. A similar pattern, i.e., a pattern in which the poles were scattered over the s-plane with no clear clustering according to the phase of the leg position, could be seen in the systems related to soleus (SOL) and TA muscles which would indicate that these muscles depend on neural control mechanisms, which may involve supraspinal structures, over the whole step cycle.

  • 156.
    Harischandra, Nalin
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Knuesel, Jeremei
    EPFL.
    Kozlov, Alexander
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Bicanski, Andrej
    EPFL.
    Cabelguen, Jean-Marie
    Neurocentre Magendie, Bordeaux University, Bordeaux Cedex, France.
    Ijspeert, Auke
    EPFL.
    Ekeberg, Örjan
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Sensory feedback plays a significant role in generating walking gait and in gait transition in salamanders: a simulation study2011Ingår i: Frontiers in Neurorobotics, ISSN 1662-5218, Vol. 5, s. 3:1-3:13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Here, we investigate the role of sensory feedback in gait generation and transition by using a three-dimensional, neuro-musculo-mechanical model of a salamander with realistic physical parameters. Activation of limb and axial muscles were driven by neural output patterns obtained from a central pattern generator (CPG) which is composed of simulated spiking neurons with adaptation. The CPG consists of a body-CPG and four limb-CPGs that are interconnected via synapses both ipsilaterally and contralaterally. We use the model both with and without sensory modulation and four different combinations of ipsilateral and contralateral coupling between the limb-CPGs. We found that the proprioceptive sensory inputs are essential in obtaining a coordinated lateral sequence walking gait (walking). The sensory feedback includes the signals coming from the stretch receptor like intraspinal neurons located in the girdle regions and the limb stretch receptors residing in the hip and scapula regions of the salamander. On the other hand, walking trot gait (trotting) is more under central (CPG) influence compared to that of the peripheral or sensory feedback. We found that the gait transition from walking to trotting can be induced by increased activity of the descending drive coming from the mesencephalic locomotor region and is helped by the sensory inputs at the hip and scapula regions detecting the late stance phase. More neurophysiological experiments are required to identify the precise type of mechanoreceptors in the salamander and the neural mechanisms mediating the sensory modulation.

  • 157. 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.

  • 158.
    Hellgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Blackwell, K.T
    Organization of synatic inputs to striatal fast spiking interneurons2002Konferensbidrag (Refereegranskat)
  • 159.
    Hellgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Grillner, S
    Lansner, A
    Computer simulation of the segmental neural network generating locomotion in lamprey by using populations of network interneurons1992Ingår i: Biological Cybernetics, ISSN 0340-1200, E-ISSN 1432-0770, Vol. 68, s. 1-13Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Realistic computer simulations of the experimentally established local spinal cord neural network generating swimming in the lamprey have been performed. Populations of network interneurons were used in which cellular properties, like cell size and membrane conductance including voltage dependent ion channels were randomly distributed around experimentally obtained mean values, as were synaptic conductances (kainate/AMPA, NMDA, glycine) and delays. This population model displayed more robust burst activity over a wider frequency range than the more simple subsample model used previously, and the pattern of interneuronal activity was appropriate. The strength of the reciprocal inhibition played a very important role in the regulation of burst frequency, and just by changing the inhibitory bias the entire physiological range could be covered. At the lower frequency range of bursting the segmental excitatory interneurons provide stability as does the activation of voltage dependent NMDA receptors. Spike frequency adaptation by means of summation of afterhyperpolarization (AHP) serves as a major burst terminating factor, and at lower rates the membrane properties conferred by the NMDA receptor activation. The lateral interneurons were not of critical importance for the burst termination. They may, however, be of particular importance for inducing a rapid burst termination during for instance steering and righting reactions. Several cellular factors combine to provide a secure and stable motor pattern in the entire frequency range.

  • 160.
    Hellgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Kellerth, J-O
    A physiological study of the monosynaptic reflex responses of cat spinal alpha-motoneurons after lumbusacral deafferentation1989Ingår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 488, s. 149-162Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In adult cats the whole S1 and rostral half of the L7 dorsal roots were cut on the left side of the spinal cord to produce a partial monosynaptic deafferentation of the ipsilateral alpha-motoneurons. Three, 6 or 12 weeks later, monosynaptic reflexes (MSRs) were recorded from the L6, L7 and S1 ventral roots or from various peripheral nerves during stimulation of the L6 and remaining parts of the L7 dorsal roots. Also, monosynaptic excitatory postsynaptic potentials (EPSPs) were recorded intracellularly in different types of medial gastrocnemius alpha-motoneurons of the L7 segment during stimulation of various hind limb muscle nerves. The right side with an identical acute deafferentation served as control. On the chronically lesioned side the MSRs were increased in size, also during post-tetanic potentiation. The monosynaptic EPSPs had increased amplitudes in all motoneuron types, but the relation in EPSP size between different motoneuron types as well as between different synergistic inputs remained largely unchanged. EPSP rise times were not changed, and aberrant monosynaptic connections from non-synergist muscles were not observed. It is concluded that the extent of reactive reflex changes may be related to both the number of vacant synaptic sites and the degree of functional synergism between the eliminated and remaining monosynaptic pathways. Possible underlying mechanisms are discussed.

  • 161.
    Hellgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Kellerth, J-O
    Reflex plasticity following lesion of afferent input versus target neurons1987Konferensbidrag (Refereegranskat)
  • 162.
    Hellgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Plenz, D.
    Blackwell, K. T.
    The role of background synaptic noise in striatal fast spiking interneurons2005Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 65, s. 727-732Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Striatal fast spiking (FS) interneurons provide inhibition to each other as well as to medium spiny projection (SP) neurons. They exhibit up-states synchronously with SP neurons, and receive GABAergic and AMPA synaptic input during both up- and down-states. The synaptic input during down-states can be considered noise and might affect detection of up-states. We investigate what role this background noise might play for up-state firing in a 127 compartment FS model neuron. The model has Na, KDr and KA conductances, and is activated through AMPA and GABA synapses. The model's response to current injection and synaptic inputs resembled experimental data. We show that intermediate levels of noise neither facilitates nor degrades the ability of the FS neuron model to detect up-states.

  • 163.
    Hellgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Plenz, D.
    Blackwell, K. T.
    Using potassium currents to solve signal-to-noise problems in inhibitory feedforward networks of the striatum2006Ingår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 95, nr 1, s. 331-341Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Using potassium currents to solve signal-to-noise problems in inhibitory feedforward networks of the striatum. J Neurophysiol 95: 331 - 341, 2006. First published September 28, 2005; doi: 10.1152/jn. 00063.2005. Fast-spiking (FS) interneurons provide the main route of feedforward inhibition from cortex to spiny projection neurons in the striatum. A steep current-firing frequency curve and a dense local axonal arbor suggest that even small excitatory inputs could translate into powerful feedforward inhibition, although such an arrangement is also sensitive to amplification of spurious synaptic inputs. We show that a transient potassium (KA) current allows the FS interneuron to strike a balance between sensitivity to correlated input and robustness to noise, thereby increasing its signal-to-noise ratio (SNR). First, a compartmental FS neuron model was created to match experimental data from striatal FS interneurons in cortex - striatum - substantia nigra organotypic cultures. Densities of sodium, delayed rectifier, and KA channels were optimized to replicate responses to somatic current injection. Spontaneous alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and gamma-aminobutyric acid ( GABA) synaptic currents were adjusted to the experimentally measured amplitude, rise time, and interevent interval histograms. Second, two additional adjustments were required to emulate the remaining experimental observations. GABA channels were localized closer to the soma than AMPA channels to match the synaptic population reversal potential. Correlation among inputs was required to produce the observed firing rate during up-states. In this final model, KA channels were essential for suppressing down-state spikes while allowing reliable spike generation during up-states. This mechanism was particularly important under conditions of high dopamine. Our results suggest that KA channels allow FS interneurons to operate without a decrease in SNR during conditions of increased dopamine, as occurs in response to reward or anticipated reward.

  • 164.
    Hellgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Tegner, J
    Lansner, A
    Grillner, S
    Control of burst proportion and frequency range by drive-dependent modulation of adaptation1999Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 26-27, s. 185-191Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Factors controlling burst proportion in oscillatory networks are analyzed. This question is motivated by the lamprey swimming motor pattern which, independently on burst frequency, is characterized by a constant burst proportion. We investigate the effect of active modulation of the relative influence of a slower and faster adaptation controlling the depolarized phase. Using Morris–Lecar oscillators, NMDA-dependent oscillations or a network of mutually excitatory neurons, it is shown that the burst proportion can be controlled by increasing what corresponds to adaptation. Oscillations occur over an extended range of background stimulation values, leading to a higher maximal frequency.

  • 165.
    Hellgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Wadden, A
    Lansner, A
    Grillner, S
    A continuous network model of the lamprey swimming rhythm generator - intersegmental coordination1994Konferensbidrag (Refereegranskat)
  • 166.
    Herman, Pawel Andrzej
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm University.
    Lundqvist, Mikael
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm University.
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Stockholm University.
    Nested theta to gamma oscillations and precise spatiotemporal firing during memory retrieval in a simulated attractor network2013Ingår i: Brain Research, ISSN 0006-8993, E-ISSN 1872-6240, Vol. 1536, nr SI, s. 68-87Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Nested oscillations, where the phase of the underlying slow rhythm modulates the power of faster oscillations, have recently attracted considerable research attention as the increased phase-coupling of cross-frequency oscillations has been shown to relate to memory processes. Here we investigate the hypothesis that reactivations of memory patterns, induced by either external stimuli or internal dynamics, are manifested as distributed cell assemblies oscillating at gamma-like frequencies with life-times on a theta scale. For this purpose, we study the spatiotemporal oscillatory dynamics of a previously developed meso-scale attractor network model as a correlate of its memory function. The focus is on a hierarchical nested organization of neural oscillations in delta/theta (2-5Hz) and gamma frequency bands (25-35Hz), and in some conditions even in lower alpha band (8-12Hz), which emerge in the synthesized field potentials during attractor memory retrieval. We also examine spiking behavior of the network in close relation to oscillations. Despite highly irregular firing during memory retrieval and random connectivity within each cell assembly, we observe precise spatiotemporal firing patterns that repeat across memory activations at a rate higher than expected from random firing. In contrast to earlier studies aimed at modeling neural oscillations, our attractor memory network allows us to elaborate on the functional context of emerging rhythms and discuss their relevance. We provide support for the hypothesis that the dynamics of coherent delta/theta oscillations constitute an important aspect of the formation and replay of neuronal assemblies. This article is part of a Special Issue entitled Neural Coding 2012.

  • 167.
    Herman, Pawel
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Odor recognition framework for evaluating olfactory codes2011Konferensbidrag (Övrigt vetenskapligt)
  • 168.
    Herman, Pawel
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lundqvist, Mikael
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Oscillations in a simulated meso-scale memory network: origin and function of theta to gamma rhythmsArtikel i tidskrift (Övrigt vetenskapligt)
  • 169. Hill, R
    et al.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Grillner, S
    Whole cell voltage clamp techniques in intact lamprey spinal cord and brainstem1994Konferensbidrag (Refereegranskat)
  • 170. Hjorth, J
    et al.
    Blackwell, K.T.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    FS networks as population detectors of correlated input activity2010Konferensbidrag (Refereegranskat)
  • 171.
    Hjorth, Johannes
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Computer Modelling of Neuronal Interactions in the Striatum2009Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Large parts of the cortex and the thalamus project into the striatum,which serves as the input stage of the basal ganglia. Information isintegrated in the striatal neural network and then passed on, via themedium spiny (MS) projection neurons, to the output stages of thebasal ganglia. In addition to the MS neurons there are also severaltypes of interneurons in the striatum, such as the fast spiking (FS)interneurons. I focused my research on the FS neurons, which formstrong inhibitory synapses onto the MS neurons. These striatal FSneurons are sparsely connected by electrical synapses (gap junctions),which are commonly presumed to synchronise their activity.Computational modelling with the GENESIS simulator was used toinvestigate the effect of gap junctions on a network of synapticallydriven striatal FS neurons. The simulations predicted a reduction infiring frequency dependent on the correlation between synaptic inputsto the neighbouring neurons, but only a slight synchronisation. Thegap junction effects on modelled FS neurons showing sub-thresholdoscillations and stuttering behaviour confirm these results andfurther indicate that hyperpolarising inputs might regulate the onsetof stuttering.The interactions between MS and FS neurons were investigated byincluding a computer model of the MS neuron. The hypothesis was thatdistal GABAergic input would lower the amplitude of back propagatingaction potentials, thereby reducing the calcium influx in thedendrites. The model verified this and further predicted that proximalGABAergic input controls spike timing, but not the amplitude ofdendritic calcium influx after initiation.Connecting models of neurons written in different simulators intonetworks raised technical problems which were resolved by integratingthe simulators within the MUSIC framework. This thesis discusses theissues encountered by using this implementation and gives instructionsfor modifying MOOSE scripts to use MUSIC and provides guidelines forachieving compatibility between MUSIC and other simulators.This work sheds light on the interactions between striatal FS and MSneurons. The quantitative results presented could be used to developa large scale striatal network model in the future, which would beapplicable to both the healthy and pathological striatum.

  • 172.
    Hjorth, Johannes
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Blackwell, Kim T
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Gap Junctions between Striatal Fast-Spiking Interneurons Regulate Spiking Activity and Synchronization as a Function of Cortical Activity2009Ingår i: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 29, nr 16, s. 5276-5286Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Striatal fast-spiking (FS) interneurons are interconnected by gap junctions into sparsely connected networks. As demonstrated for cortical FS interneurons, these gap junctions in the striatum may cause synchronized spiking, which would increase the influence that FS neurons have on spiking by the striatal medium spiny (MS) neurons. Dysfunction of the basal ganglia is characterized by changes in synchrony or periodicity, thus gap junctions between FS interneurons may modulate synchrony and thereby influence behavior such as reward learning and motor control. To explore the roles of gap junctions on activity and spike synchronization in a striatal FS population, we built a network model of FS interneurons. Each FS connects to 30-40% of its neighbors, as found experimentally, and each FS interneuron in the network is activated by simulated corticostriatal synaptic inputs. Our simulations show that the proportion of synchronous spikes in FS networks with gap junctions increases with increased conductance of the electrical synapse; however, the synchronization effects are moderate for experimentally estimated conductances. Instead, the main tendency is that the presence of gap junctions reduces the total number of spikes generated in response to synaptic inputs in the network. The reduction in spike firing is due to shunting through the gap junctions; which is minimized or absent when the neurons receive coincident inputs. Together these findings suggest that a population of electrically coupled FS interneurons may function collectively as input detectors that are especially sensitive to synchronized synaptic inputs received from the cortex.

  • 173.
    Hjorth, Johannes
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Blackwell, Kim T.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Gap junctions on striatal fast spiking interneurons reduce firing for non-correlated inputs2008Konferensbidrag (Refereegranskat)
  • 174.
    Hjorth, Johannes
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Elias, Alex Hanna
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    The significance of gap junction location in striatal fast spiking interneurons2007Ingår i: Neurocomputing, ISSN 0925-2312, E-ISSN 1872-8286, Vol. 70, nr 10-12, s. 1887-1891Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Fast spiking (FS) interneurons in the striatunt are hypothesised to control spike timing in the numerous medium spiny (MS) projection neurons by inhibiting or delaying firing in the MS neurons. The FS neurons are connected to each other through electrical gap junctions. This might synchronise the FS neurons, leading to increased influence on target neurons. Here, we explore the possible difference between proximal and distal gap junction locations. Somatic and distal dendritic gap junctions with equal effective coupling coefficient, as defined for steady-state somatic inputs, showed significantly different effective coupling coefficient with transient inputs. However, the ability to synchronise spiking in pairwise coupled FS neurons, which received synaptic inputs as during striatal up-state periods, was as effective with distal gap junctions as with proximal ones. Proximal gap junctions, however, caused synchronisation within a more precise time window.

  • 175.
    Hjorth, Johannes
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Hedlund, Lennart
    KTH, Skolan för datavetenskap och kommunikation (CSC).
    Blackwell, Kim T
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Synchronization Effects in Networks of Striatal Fast Spiking Interneurons - Role of Gap Junctions2008Ingår i: ADVANCES IN COGNITIVE NEURODYNAMICS, PROCEEDINGS / [ed] Wang R, Gu F, Shen E, TOTOWA: HUMANA PRESS INC , 2008, s. 63-66Konferensbidrag (Refereegranskat)
    Abstract [en]

    Recent studies have found gap junctions between striatal fast spiking interneurons (FSN). Gap junctions between neocortical FSNs cause increased synchrony of firing in response to current injection, but the effect of gap junctions in response to synaptic input is unknown. To explore this issue, we built a network model of FSNs. Each FSN connects to 30-40% of its neighbours, as found experimentally, and each FSN in the network is activated by simulated up-state synaptic inputs. Simulation experiments show that the proportion of synchronous spikes in coupled FSNs increases with gap junction conductance. Proximal gap junctions increase the synchronization more than distal gap junctions. During up-states the synchronization effects in FSNs coupled pairwise with proximal gap junctions are small for experimentally estimated gap junction conductances; however, higher order correlations are significantly increased in larger FSN networks.

  • 176.
    Hjorth, Johannes
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Klaus, Andreas
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    The influence of stuttering properties for firing activity in pairs of electrically coupled striatal fast-spiking interneurons2009Ingår i: Neuroinformatics 2009. Pilsen, Czech Republic, September 06 - 08,  2009, 2009Konferensbidrag (Övrigt vetenskapligt)
    Abstract [en]

    The striatum is the main input stage of the basal ganglia system, which is involved in executive functions of the forebrain – such as the planning and the selection of motor behavior. Feedforward inhibition of medium-sized spiny projection neurons in the striatum by fast-spiking interneurons is supposed to be an important determinant of controlling striatal output to later stages of the basal ganglia [1]. Striatal fast-spiking interneurons, which constitute approximately 1-2 % of all striatal neurons, show many similarities to cortical fast-spiking cells. In response to somatic current injection, for example, some of these neurons exhibit spike bursts with a variable number of action potentials (so called stuttering) [2-4]. Interestingly, the membrane potential between such stuttering episodes oscillates in the range of 20-100 Hz [3,5]. The first spike of each stuttering episode invariably occurs at a peak of the underlying subthreshold oscillation. In both cortex and striatum, fast-spiking cells have been shown to be inter-connected by gap junctions [6,7]. In vitro measurements as well as theoretical studies indicate that electrical coupling via gap junctions might be able to promote synchronous activity among these neurons [6,8].Here we use computational modeling to investigate how the presence of subthreshold oscillations and stuttering properties influence the synchronization of activity in pairs of electrically coupled fast-spiking neurons. We use the model of Golomb et al. [3], which we have extended with a dendritic tree in order to be able to simulate distal synaptic input. We show that gap junctions are able to synchronize both subthreshold membrane potential fluctuations as well as the stuttering periods in response to somatic current injection. In response to synaptic input, however, our model neuron rarely shows subthreshold oscillations, and the stuttering behavior changes to a firing pattern with single spikes or spike doublets. We furthermore investigate the effect of GABAergic (i.e. inhibitory) input to the model of the fast-spiking neuron and predict that inhibitory input is able to induce overlapping stuttering episodes in these cells. We finally discuss our results in the context of the feedforward inhibitory network which is likely to play an important role in striatal and basal ganglia function.

  • 177. Hjorth, Johannes
    et al.
    Krieger, P
    Oliveira, R.F.
    Blackwell, Kim T
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    GABAergic control of dendritic calcium dynamics in striatal medium spiny neurons2008Konferensbidrag (Refereegranskat)
    Abstract [en]

    Experiments have demonstrated the ability of action potentials to actively backpropagate in striatal medium spiny (MS) neurons, affecting the calcium levels in the dendrites [1, 2, 3]. Increased calcium levels trigger changes in plasticity [4, 5], which is important for learning and other functions [6]. Studies in the hippocampus have shown that GABAergic input can modulate the backpropagation of action potentials from the soma to the distal dendrites [7]. The MS neurons receive both proximal feedforward GABAergic inhibition from fast spiking interneurons (FS), and distal feedback inhibition from other neighbouring MS neurons. In the present study the effect of GABAergic inputs on the dendritic calcium dynamics is investigated.

  • 178.
    Hjorth, Johannes
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Zilberter, M
    Oliveria, R.F.
    Blackwell, Kim T.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    GABAergic control of backpropagating action potentials in striatal medium spiny neurons2008Konferensbidrag (Refereegranskat)
    Abstract [en]

    Experiments have demonstrated the ability of action potentials to actively backpropagate in striatal medium spiny (MS) neurons, affecting the calcium levels in the dendrites[1-3]. Increased calcium levels trigger changes in plasticity[4,5], which is important for learning and other functions[6]. Studies in the hippocampus have shown that GABAergic input can modulate the backpropagation of action potentials from the soma to the distal dendrites[7]. The MS neurons receive both proximal feedforward GABAergic inhibition from fast spiking interneurons (FS), and distal feedback inhibition from other neighbouring MS neurons. In the present study the effect of these GABAergic inputs on the dendritic calcium dynamics is investigated.

  • 179.
    Holme, Petter
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Model validation of simple-graph representations of metabolism2009Ingår i: Journal of the Royal Society Interface, ISSN 1742-5689, E-ISSN 1742-5662, Vol. 6, nr 40, s. 1027-1034Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The large-scale properties of chemical reaction systems, such as metabolism, can be studied with graph-based methods. To do this, one needs to reduce the information, lists of chemical reactions, available in databases. Even for the simplest type of graph representation, this reduction can be done in several ways. We investigate different simple network representations by testing how well they encode information about one biologically important network structure-network modularity (the propensity for edges to be clustered into dense groups that are sparsely connected between each other). To achieve this goal, we design a model of reaction systems where network modularity can be controlled and measure how well the reduction to simple graphs captures the modular structure of the model reaction system. We find that the network types that best capture the modular structure of the reaction system are substrate-product networks (where substrates are linked to products of a reaction) and substance networks (with edges between all substances participating in a reaction). Furthermore, we argue that the proposed model for reaction systems with tunable clustering is a general framework for studies of how reaction systems are affected by modularity. To this end, we investigate statistical properties of the model and find, among other things, that it recreates correlations between degree and mass of the molecules.

  • 180.
    Holme, Petter
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Signatures of Currency Vertices2009Ingår i: Journal of the Physical Society of Japan, ISSN 0031-9015, E-ISSN 1347-4073, Vol. 78, nr 3, s. 034801-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Many real-world networks have broad degree distributions. For some systems, this means that the functional of the vertices is also broadly distributed, in other cases the vertices are equally significant, but in different ways. One example of the latter case is metabolic networks, where the high-degree vertices the currency metabolites-supply the molecular groups to the low-degree metabolites, and the latter are responsible for the higher-order biological function, Of Vital importance to the organism. In this paper, we propose a generalization of currency metabolites to currency vertices. We investigate the network structural characteristics of such systems, both in model networks and in sonic empirical systems. fit addition to metabolic networks, we find that a network of music collaborations and a network of e-mail exchange could be described by a division of the vertices into currency vertices and others.

  • 181.
    Holme, Petter
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Huss, Mikael
    Comment on "Regularizing capacity of metabolic networks"2008Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In a recent paper, Marr, Muller-Linow, and Hutt [Phys. Rev. E 75, 041917 (2007)] investigate an artificial dynamic system on metabolic networks. They find a less complex time evolution of this dynamic system in real networks, compared to networks of null models. The authors argue that this suggests that metabolic network structure is a major factor behind the stability of biochemical steady states. We reanalyze the same kind of data using a dynamic system modeling actual reaction kinetics. The conclusions about stability, from our analysis, are inconsistent with those of Marr We argue that this issue calls for a more detailed type of modeling.

  • 182.
    Holme, Petter
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Karlin, Josh
    Forrest, Stephanie
    An integrated model of traffic, geography and economy in the internet2008Ingår i: Computer communication review, ISSN 0146-4833, E-ISSN 1943-5819, Vol. 38, nr 3, s. 7-15Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Modeling Internet growth is important both for understanding the current network and to predict and improve its future. To date, Internet models have typically attempted to explain a subset of the following characteristics: network structure, traffic flow, geography, and economy. In this paper we present a discrete, agent-based model, that integrates all of them. We show that the model generates networks with topologies, dynamics, and more speculatively spatial distributions that are similar to the Internet.

  • 183.
    Holme, Petter
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Kim, Beom Jun
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fodor, Viktoria
    KTH, Skolan för elektro- och systemteknik (EES), Kommunikationsnät.
    Heterogeneous attachment strategies optimize the topology of dynamic wireless networks2010Ingår i: European Physical Journal B: Condensed Matter Physics, ISSN 1434-6028, E-ISSN 1434-6036, Vol. 73, nr 4, s. 597-604Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    In optimizing the topology of wireless networks built of a dynamic set of spatially embedded agents, there are many trade-offs to be dealt with. The network should preferably be as small (in the sense that the average, or maximal, pathlength is short) as possible, it should be robust to failures, not consume too much power, and so on. In this paper, we investigate simple models of how agents can choose their neighbors in such an environment. In our model of attachment, we can tune from one situation where agents prefer to attach to others in closest proximity, to a situation where agents attach to random others regardless of distance (which thus are, on average, further away than the connections to the spatial neighbors). We evaluate this scenario with several performance measures and find that the optimal topologies, for most of the quantities, is obtained for strategies resulting in a mix of most local and a few random connections.

  • 184.
    Holst, Anders
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Swedish Institute of Computer Science, Sweden.
    Bohlin, M.
    Ekman, J.
    Sellin, O.
    Lindström, B.
    Larsen, S.
    Statistical anomaly detection for train fleets2013Ingår i: The AI Magazine, ISSN 0738-4602, Vol. 34, nr 1, s. 33-42Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    We have developed a method for statistical anomaly detection that has been deployed in a tool for condition monitoring of train fleets. The tool is currently used by several railway operators across the world to inspect and visualize the occurrence of "event messages" generated on the trains. The anomaly detection component helps the operators quickly to find significant deviations from normal behavior and to detect early indications for possible problems. The method used is based on Bayesian principal anomaly, which is a framework for parametric anomaly detection using Bayesian statistics. The savings in maintenance costs of using the tool comes mainly from avoiding costly breakdowns and have been estimated to be several million Euros per year for the tool. In the long run, it is expected that maintenance costs can be reduced by between 5 and 10 percent with the help of the tool.

  • 185.
    Huss, Mikael
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA. KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Wallén, Peter
    Department of Neuroscience, Nobel Institute for Neurophysiology, Karolinska Institutet.
    El Manira, Abdeljabbar
    Department of Neuroscience, Nobel Institute for Neurophysiology, Karolinska Institutet.
    Grillner, Sten
    Department of Neuroscience, Nobel Institute for Neurophysiology, Karolinska Institutet.
    Hellgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Roles of ionic currents in lamprey CPG neurons: a modeling study2007Ingår i: Journal of Neurophysiology, ISSN 0022-3077, E-ISSN 1522-1598, Vol. 97, nr 4, s. 2696-2711Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The spinal network underlying locomotion in the lamprey consists of a core network of glutamatergic and glycinergic interneurons, previously studied experimentally and through mathematical modeling. We present a new and more detailed computational model of lamprey locomotor network neurons, based primarily on detailed electrophysiological measurements and incorporating new experimental findings. The model uses a Hodgkin Huxley-like formalism and consists of 86 membrane compartments containing 12 types of ion currents. One of the goals was to introduce a fast, transient potassium current (K-t) and two sodium-dependent potassium currents, one faster (K-NaF) and one slower (K-NaS), in the model. Not only has the model lent support to the interpretation of experimental results but it has also provided predictions for further experimental analysis of single-network neurons. For example, K-t was shown to be one critical factor for controlling action potential duration. In addition, the model has proved helpful in investigating the possible influence of the slow afterhyperpolarization on repetitive firing during ongoing activation. In particular, the balance between the simulated slow sodium-dependent and calcium-dependent potassium currents has been explored, as well as the possible involvement of dendritic conductances.

  • 186.
    Huss, Mikael
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA. KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lansner, Anders
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Wallén, Peter
    El Manira, Abdeljabbar
    Grillner, Sten
    Kotaleski, Jeanette Hellgren
    KTH, Skolan för datavetenskap och kommunikation (CSC), Numerisk Analys och Datalogi, NADA.
    Functional roles of ionic currents in lamprey CPG neurons: a model studyManuskript (preprint) (Övrigt vetenskapligt)
  • 187.
    Hällgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Modelling of motor systems including the dynamics in intracellular signaling networks involved in learning and synaptic plasticity2009Konferensbidrag (Övrigt vetenskapligt)
  • 188.
    Hällgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Subcellular temporal computation and its role for synaptic plasticity2007Konferensbidrag (Övrigt vetenskapligt)
  • 189.
    Hällgren Kotaleski, Jeanette
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    The functions of the striatal microcircuitry: a modeling approach2010Konferensbidrag (Övrigt vetenskapligt)
  • 190.
    Hällgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Blackwell, Kim T.
    Modelling the molecular mechanisms of synaptic plasticity using systems biology approaches2010Ingår i: Nature Reviews Neuroscience, ISSN 1471-003X, E-ISSN 1471-0048, Vol. 11, nr 4, s. 239-251Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Synaptic plasticity is thought to underlie learning and memory, but the complexity of the interactions between the ion channels, enzymes and genes that are involved in synaptic plasticity impedes a deep understanding of this phenomenon. Computer modelling has been used to investigate the information processing that is performed by the signalling pathways involved in synaptic plasticity in principal neurons of the hippocampus, striatum and cerebellum. In the past few years, new software developments that combine computational neuroscience techniques with systems biology techniques have allowed large-scale, kinetic models of the molecular mechanisms underlying long-term potentiation and long-term depression. We highlight important advancements produced by these quantitative modelling efforts and introduce promising approaches that use advancements in live-cell imaging.

  • 191.
    Hällgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Grillner, S
    Networks in motion: bridging between intrinsic mechanisms and systems level function2010Konferensbidrag (Övrigt vetenskapligt)
  • 192.
    Hällgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lindskog, M
    Blackwell, K.T
    DARPP-32 acts as a temporal integrator: Results from a computer model2004Konferensbidrag (Övrigt vetenskapligt)
  • 193.
    Hällgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lindskog, M
    Blackwell, K.T
    Effect of temporal pattern on dopamine activated second messenger pathways2005Konferensbidrag (Övrigt vetenskapligt)
  • 194.
    Hällgren Kotaleski, Jeanette
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Plenz, D
    Blackwell, K.T.
    Background inputs and KA current influence firing of striatal fast spiking interneurons2004Konferensbidrag (Övrigt vetenskapligt)
  • 195. Iglesias, Maria Jesus
    et al.
    Reilly, Sarah-Jayne
    Emanuelsson, Olof
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Sennblad, Bengt
    Najafabadi, Mohammad Pirmoradian
    KTH, Skolan för bioteknologi (BIO), Genteknologi. KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Folkersen, Lasse
    Mälarstig, Anders
    Lagergren, Jens
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Eriksson, Per
    Hamsten, Anders
    Odeberg, Jacob
    KTH, Skolan för bioteknologi (BIO), Proteomik (stängd 20130101). KTH, Centra, Science for Life Laboratory, SciLifeLab.
    Combined Chromatin and Expression Analysis Reveals Specific Regulatory Mechanisms within Cytokine Genes in the Macrophage Early Immune Response2012Ingår i: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 7, nr 2, s. e32306-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Macrophages play a critical role in innate immunity, and the expression of early response genes orchestrate much of the initial response of the immune system. Macrophages undergo extensive transcriptional reprogramming in response to inflammatory stimuli such as Lipopolysaccharide (LPS). To identify gene transcription regulation patterns involved in early innate immune responses, we used two genome-wide approaches - gene expression profiling and chromatin immunoprecipitation-sequencing (ChIP-seq) analysis. We examined the effect of 2 hrs LPS stimulation on early gene expression and its relation to chromatin remodeling (H3 acetylation; H3Ac) and promoter binding of Sp1 and RNA polymerase II phosphorylated at serine 5 (S5P RNAPII), which is a marker for transcriptional initiation. Our results indicate novel and alternative gene regulatory mechanisms for certain proinflammatory genes. We identified two groups of upregulated inflammatory genes with respect to chromatin modification and promoter features. One group, including highly up-regulated genes such as tumor necrosis factor (TNF), was characterized by H3Ac, high CpG content and lack of TATA boxes. The second group, containing inflammatory mediators (interleukins and CCL chemokines), was up-regulated upon LPS stimulation despite lacking H3Ac in their annotated promoters, which were low in CpG content but did contain TATA boxes. Genome-wide analysis showed that few H3Ac peaks were unique to either +/-LPS condition. However, within these, an unpacking/expansion of already existing H3Ac peaks was observed upon LPS stimulation. In contrast, a significant proportion of S5P RNAPII peaks (approx 40%) was unique to either condition. Furthermore, data indicated a large portion of previously unannotated TSSs, particularly in LPS-stimulated macrophages, where only 28% of unique S5P RNAPII peaks overlap annotated promoters. The regulation of the inflammatory response appears to occur in a very specific manner at the chromatin level for specific genes and this study highlights the level of fine-tuning that occurs in the immune response.

  • 196.
    Innocenti, Nicolas
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Data Analysis and Next Generation Sequencing : Applications in Microbiology.2015Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Next Generation Sequencing (NGS) is a new technology that has revolutionized the way we study living organisms. Where previously only a few genes could be studied at a time through targeted direct probing, NGS offers the possibility to perform measurements for a whole genome at once. The drawback is that the amount of data generated in the process is large and extracting useful information from it requires new methods to process and analyze it.

    The main contribution of this thesis is the development of a novel experimental method coined tagRNA-seq, combining 5’tagRACE, a previously developed technique, with RNA-sequencing technology. Briefly, tagRNA-seq makes it possible to identify the 5’ ends of RNAs in bacteria and directly probe for their type, primary or processed, by ligating short RNA sequences, the tags, to the beginnings of RNA molecules. We used the method to directly probe for transcription start and processing sites in two bacterial species, Escherichiacoli and Enterococcus faecalis. It was also used to study polyadenylation in E. coli, where the ability to identify processed RNA molecules proved to be useful to separate direct and indirect regulatory effects of this mechanism. We also demonstrate how data from tagRNA-seq experiments can be used to increase confidence on the discovery of anti-sense transcripts in bacteria. Analyses of RNA-seq data obtained in the context of these experiments revealed subtle artifacts in the coverage signal towards gene ends, that we were able to explain and quantify based Kolmogorov’s broken stick model. We also discovered evidences for circularization of a few RNA transcripts, both in our own data sets and publicly available data.

    Designing the tags used in tagRNA-seq led us to the problem of words absent from a text. We focus on a particular subset of these, the minimal absent words (MAWs), and develop a theory providing a complete description of their size distribution in random text. We also show that MAWs in genomes from viruses and living organisms almost always exhibit a behavior different from random texts in the tail of the distribution, and that MAWs from this tail are closely related to sequences present in the genome that preferentially appear in regions with important regulatory functions.

    Finally, and independently from tagRNA-seq, we propose a new approach to the problem of bacterial community reconstruction in metagenomic, based on techniques from compressed sensing. We provide a novel algorithm competing with state-of-the-art techniques in the field.

  • 197.
    Innocenti, Nicolas
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. KTH, Skolan för informations- och kommunikationsteknik (ICT), Mikroelektronik och tillämpad fysik, MAP.
    What microcavities can do in photonics : coupling resonances and optical gain2009Självständigt arbete på avancerad nivå (masterexamen), 20 poäng / 30 hpStudentuppsats (Examensarbete)
    Abstract [en]

    The present master's thesis deals with numerical modeling of solid-state micrometrical-sized polymeric dye lasers, commonly denoted as microcavities. It is part of a large research initiative carried out in the optics group, at the MAP (Microelectronics and Applied Physics) department in KTH (Kungliga Tekniska Högskolan - Royal Technical School) and targeted towards the design and manufacturing of micro- and nano-scaled polymeric components for nano-photonics, primarily lasers. The finite element method (FEM) in frequency domain is used as a primary modeling tool through the simulation software COMSOL Multiphysics. Models for spontaneous emission, optical losses and gain are developed and demonstrated. A specic layout is studied: the double hexagonal microcavity. While it was expected to be a good candidate for a laser, the design shows unexpected properties making it useful for sensing applications. Finally, the transposition of models to time domain is initiated : a replacement solution for the lacking perfectly matched layer (PML) in Comsol is developed and demonstrated. Methods for modeling materials parameters in time domain are investigated, together with the possible use of a more suitable algorithm : finite dierences in time domain (FDTD) or Yee's scheme.

  • 198.
    Innocenti, Nicolas
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Lognormality and oscillations in the coverage of high-throughput transcriptomic data towards gene ends2013Ingår i: Journal of Statistical Mechanics: Theory and Experiment, ISSN 1742-5468, E-ISSN 1742-5468, Vol. 2013, nr 10, s. P10013-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    High-throughput transcriptomics experiments have reached the stage where the count of the number of reads alignable to a given position can be treated as an almost-continuous signal. This allows us to ask questions of biophysical/biotechnical nature, but which may still have biological implications. Here we show that when sequencing RNA fragments from one end, as is the case on most platforms, an oscillation in the read count is observed at the other end. We further show that these oscillations can be well described by Kolmogorov's 1941 broken stick model. We investigate how the model can be used to improve predictions of gene ends (3' transcript ends), but conclude that with present data the improvement is only marginal. The results highlight subtle effects in high-throughput transcriptomics experiments which do not have a biological origin, but which may still be used to obtain biological information.

  • 199.
    Innocenti, Nicolas
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Golumbeanu, Monica
    Department of Biosystems Science and Engineering, ETH Zürich, CH-4058, Basel, Switzerland.
    Fouquier d'Hérouël, Aymeric
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB. Luxembourg Centre for Systems Biomedicine, University of Luxembourg, L-4362, Esch-sur-Alzette, Luxembourg.
    Lacoux, Caroline
    INRA, UMR1319 Micalis, Domaine de Vilvert, F-78352, Jouy-en-Josas, France.
    Bonnin, Rémy A.
    Institut de Génétique et Microbiologie, Université Paris-Sud, CNRS, UMR8621, F-91405, Orsay, France.
    Kennedy, Sean P.
    INRA, MetaGenoPolis US1367, Domaine de Vilvert, F-78350, Jouy-en-Josas, France.
    Wessner, Francoise
    INRA, UMR1319 Micalis, Domaine de Vilvert, F-78352, Jouy-en-Josas, France.
    Serror, Pascale
    INRA, UMR1319 Micalis, Domaine de Vilvert, F-78352, Jouy-en-Josas, France.
    Bouloc, Philippe
    Institut de Génétique et Microbiologie, Université Paris-Sud, CNRS, UMR8621, F-91405, Orsay, France.
    Repoila, Francis
    INRA, UMR1319 Micalis, Domaine de Vilvert, F-78352, Jouy-en-Josas, France.
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Whole-genome mapping of 5′ RNA ends in bacteria by tagged sequencing: a comprehensive view in Enterococcus faecalis2015Ingår i: RNA, ISSN 1355-8382Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Enterococcus faecalis is the third cause of nosocomial infections. To obtain the first snapshot of transcriptional organizations in this bacterium, we used a modified RNA-seq approach enabling to discriminate primary from processed 5' RNA ends. We also validated our approach by confirming known features in Escherichia coli. We mapped 559 transcription start sites (TSSs) and 352 processing sites (PSSs) in E. faecalis. A blind motif search retrieved canonical features of SigA-and SigN-dependent promoters preceding transcription start sites mapped. We discovered 85 novel putative regulatory RNAs, small-and antisense RNAs, and 72 transcriptional antisense organizations. Presented data constitute a significant insight into bacterial RNA landscapes and a step toward the inference of regulatory processes at transcriptional and post-transcriptional levels in a comprehensive manner.

  • 200.
    Innocenti, Nicolas
    et al.
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Nguyen, Hoang-Son
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    Fouquier d'Hérouël, Aymeric
    Luxembourg Centre for Systems Biomedicine, University of Luxembourg.
    Aurell, Erik
    KTH, Skolan för datavetenskap och kommunikation (CSC), Beräkningsbiologi, CB.
    An observation of circular RNAs in bacterial RNA-seq data.2015Manuskript (preprint) (Övrigt vetenskapligt)
    Abstract [en]

    Circular RNAs (circRNAs) are a class of RNA with an important role in micro RNA (miRNA) regulation recently discovered in Human and various other eukaryotes as well as in archaea. Here, we have analyzed RNA-seq data obtained from Enterococcus faecalis and Escherichia coli in a way similar to previous studies performed on eukaryotes. We report observations of circRNAs in RNA-seq data that are reproducible across multiple experiments performed with different protocols or growth conditions.

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