| 1. |
- Alfven, Gösta, et al.
(author)
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Review of childhood pain highlights the role of negative stress.
- 2019
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In: Acta Paediatrica. - : Wiley-Blackwell. - 0803-5253 .- 1651-2227. ; 108:12, s. 2148-2156
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Research review (peer-reviewed)abstract
- AIM: Recurrent pain of unknown origin is a major problem in children. The aim of the present review was to examine the hypothesis of negative stress as an aetiology of recurrent pain from different aspects.METHODS AND RESULTS: Epidemiological studies, clinical experience and hormonal data give support for such a hypothesis. Negative stress as a tentative aetiology for recurrent pain is reviewed. Stress, muscular tension, the startle reaction and its tentative relation to pain is illuminated. Deviations of hormonal secretion supporting a stress aetiology is mentioned. The role of central sensitization for recurrent pain is discussed. Possible aetiological implications of recurrent pain as a local symptom or a general disorder are presented. Brain changes due to stress is shortly reviewed. Stress and pain in the clinic are highlighted. The importance of biological, psychological and social factors, as well as genetic elements, are-Ddiscussed.CONCLUSION: Stress elicits neurobiological mechanisms. They may lead to many neurophysiological deviances. Increase of muscle tension and neuromuscular excitability and enhanced startle reaction may be of importance for recurring pain. The identification of stress as a primary cause of recurrent pain can have huge implications for understanding signs and treatment in clinical practice. This article is protected by copyright. All rights reserved.
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| 2. |
- Athanassiadis, Tuija, 1971-
(author)
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Neural circuits engaged in mastication and orofacial nociception
- 2009
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Doctoral thesis (other academic/artistic)abstract
- A deeper understanding of both movement control and the effects of nociceptor inputs on our motor systems is critical for proper clinical diagnosis of musculo-skeletal dysfunctions and for development of novel rehabilitation schemes. In the jaw system, masticatory movements are produced by a central pattern generator (CPG) located in the brainstem. Considerable efforts have been made in deciphering this neuronal network. The present thesis contributes towards an increasingly detailed understanding of its essential elements, and presents a hypothesis of how deep somatic pain (i.e. muscle pain) may be evoked and interferes with the masticatory CPG circuitry. In Paper I, the expression of c-Fos-like protein was used as a molecular marker to visualize brainstem neurons that were active during induced fictive mastication in the anesthetized and paralyzed rabbit. Our findings provide a previously lacking detailed record of the neuronal populations that form the masticatory motor pattern. Certain cells were located in brainstem areas previously suggested to be involved in the masticatory CPG. However, it was a new finding that neurons in the dorsal part of the trigeminal main sensory nucleus (NVsnpr-d) may belong to this circuitry. Paper II focused on the discovered neurons in NVsnpr in an in vitro slice preparation from young rats. Intracellular recordings allowed us to define two cell types based on their response to depolarizing current. Microstimulation applied to the trigeminal motor nucleus, its reticular border, the parvocellular reticular formation and the nucleus reticularis pontis caudalis, elicited postsynaptic potentials in 81% of the neurons tested. Responses obtained were predominately excitatory and sensitive to gluta-matergic antagonists DNQX or/and APV. Some inhibitory and biphasic responses were also evoked. Bicuculline methiodide or strychnine blocked the IPSPs indicating that they were mediated by GABAA or glycinergic receptors. About one third of the stimulations activated both types of neurons antidromically. Neurons in NVsnpr-d seem to gather all the conditions that can theoretically account for a role in masticatory rhythm generation. In Paper III, the masticatory model system was used to investigate the possible role of muscle spindle primary afferents in development of persistent musculoskeletal pain. Following intramuscular acidic (pH 4.0) saline injections of rat masseter muscles, in vitro whole cell recordings were done from jaw closing muscle spindle somata located in the trigeminal mesencephalic nucleus (NVmes). Compared to control neurons, the somata of afferents exposed to acid had more hyperpolarized membrane potentials, more hyperpolarized thresholds for firing, high frequency membrane oscillations and ectopic bursting of action potentials. These changes in membrane properties lasted for up to 35 days. Within the same time frame experi-mental animals showed hypersensitivity to touch on the skin covering the injected muscle. Similar saline injections also resulted in a significant increase of activity dependent c-Fos expression in NVmes neurons compared to controls. Immuno-fluorescence and lectin binding studies indicated that small-caliber muscle afferents containing known nociceptor markers (CGRP, SP, P2X3, TRPV1 and IB4) and expressing glutamate receptors are found close to the annulo-spiral endings of the NVmes afferents. Combined, our new observations support the hypothesis that excessive release of glutamate, within muscle spindles due to ectopically evoked antidromic action potentials, could lead to development of persistent musculoskeletal pain by activation and/ or sensitization of adjacent muscle afferent nociceptors.
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| 3. |
- Ekeberg, Örjan, 1954-, et al.
(author)
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Simulations of neuromuscular control in lamprey swimming
- 1999
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In: Philosophical Transactions of the Royal Society of London. Biological Sciences. - : The Royal Society. - 0962-8436 .- 1471-2970. ; 354:1385, s. 895-902
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Journal article (peer-reviewed)abstract
- The neuronal generation of vertebrate locomotion has been extensively studied in the lamprey. Models at different levels of abstraction are being used to describe this system, from abstract nonlinear oscillators to interconnected model neurons comprising multiple compartments and a Hodgkin-Huxley representation of the most relevant ion channels. To study the role of sensory feedback by simulation, it eventually also becomes necessary to incorporate the mechanical movements in the models. By using simplifying models of muscle activation, body mechanics, counteracting water forces, and sensory feedback through stretch receptors and vestibular organs, we have been able to close the feedback loop to enable studies of the interaction between the neuronal and the mechanical systems. The neuromechanical simulations reveal that the currently known network is sufficient for generating a whole repertoire of swimming patterns. Swimming at different speeds and with different wavelengths, together with the performance of lateral turns can all be achieved by simply varying the brainstem input. The neuronal mechanisms behind pitch and roll manoeuvres are less clear. We have put forward a 'crossed-oscillators' hypothesis where partly separate dorsal and ventral circuits are postulated. Neuromechanical simulations of this system show that it is also capable of generating realistic pitch turns and rolls, and that vestibular signals can stabilize the posture during swimming.
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| 4. |
- Ekeberg, Örjan, 1954-, et al.
(author)
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The Neural Control of Fish Swimming studied through Numerical Simulations
- 1995
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In: Adaptive Behavior. - : SAGE Publications. - 1059-7123 .- 1741-2633. ; 3:4, s. 363-384
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Journal article (peer-reviewed)abstract
- The neuronal generation of vertebrate locomotion has been extensively studied in the lamprey. Computer simulations of this system have been carried out with different aims and with different techniques. in this article, we review some of these simulations, particularly those leading toward models that describe She interaction that occurs between the neuronal system and its mechanical environment during swimming. Here we extend these models, enabling two new experiments to be conducted. The first one addresses the role of sensory feedback by exposing the neuromechanical system to unexpected perturbations. The second one tests the validity of an earlier proposed hypothesis for the neural generation of three-dimensional (3D) steering by coupling this central pattern generator to a mechanical 3D simulation.
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| 5. |
- Frost Nylén, Johanna, et al.
(author)
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The roles of surround inhibition for the intrinsic function of the striatum, analyzed in silico
- 2023
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424 .- 1091-6490. ; 120:45
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Journal article (peer-reviewed)abstract
- The basal ganglia are important for action initiation, selection, and motor learning. The input level, the striatum, receives input preferentially from the cortex and thalamus and is to 95% composed of striatal projection neurons (SPNs) with sparse GABAergic collaterals targeting distal dendrites of neighboring SPNs, in a distance-dependent manner. The remaining 5% are GABAergic and cholinergic interneurons. Our aim here is to investigate the role of surround inhibition for the intrinsic function of the striatum. Large-scale striatal networks of 20 to 40 thousand neurons were simulated with detailed multicompartmental models of different cell types, corresponding to the size of a module of the dorsolateral striatum, like the forelimb area (mouse). The effect of surround inhibition on dendritic computation and network activity was investigated, while groups of SPNs were activated. The SPN-induced surround inhibition in distal dendrites shunted effectively the corticostriatal EPSPs. The size of dendritic plateau-like potentials within the specific dendritic segment was both reduced and enhanced by inhibition, due to the hyperpolarized membrane potential of SPNs and the reversal-potential of GABA. On a population level, the competition between two subpopulations of SPNs was found to depend on the distance between the two units, the size of each unit, the activity level in each subgroup and the dopaminergic modulation of the dSPNs and iSPNs. The SPNs provided the dominating source of inhibition within the striatum, while the fast-spiking interneuron mainly had an initial effect due to short-term synaptic plasticity as shown in with ablation of the synaptic interaction.
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| 6. |
- González-Redondo, Álvaro, et al.
(author)
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Reinforcement learning in a spiking neural model of striatum plasticity
- 2023
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In: Neurocomputing. - : Elsevier BV. - 0925-2312 .- 1872-8286. ; 548
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Journal article (peer-reviewed)abstract
- The basal ganglia (BG), and more specifically the striatum, have long been proposed to play an essential role in action-selection based on a reinforcement learning (RL) paradigm. However, some recent findings, such as striatal spike-timing-dependent plasticity (STDP) or striatal lateral connectivity, require further research and modelling as their respective roles are still not well understood. Theoretical models of spiking neurons with homeostatic mechanisms, lateral connectivity, and reward-modulated STDP have demonstrated a remarkable capability to learn sensorial patterns that statistically correlate with a rewarding signal. In this article, we implement a functional and biologically inspired network model of the striatum, where learning is based on a previously proposed learning rule called spike-timing-dependent eligibility (STDE), which captures important experimental features in the striatum. The proposed computational model can recognize complex input patterns and consistently choose rewarded actions to respond to such sensorial inputs. Moreover, we assess the role different neuronal and network features, such as homeostatic mechanisms and lateral inhibitory connections, play in action-selection with the proposed model. The homeostatic mechanisms make learning more robust (in terms of suitable parameters) and facilitate recovery after rewarding policy swapping, while lateral inhibitory connections are important when multiple input patterns are associated with the same rewarded action. Finally, according to our simulations, the optimal delay between the action and the dopaminergic feedback is obtained around 300 ms, as demonstrated in previous studies of RL and in biological studies.
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| 7. |
- Grillner, Sten, et al.
(author)
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Basal Ganglia-A Motion Perspective
- 2020
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In: Comprehensive Physiology. - : Wiley. - 2040-4603. ; 10:4, s. 1241-1275
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Journal article (peer-reviewed)abstract
- The basal ganglia represent an ancient part of the nervous system that have remained organized in a similar way over the last 500 million years and are of importance for our ability to determine which actions to choose at any given moment in time. Salient or reward stimuli act via the dopamine system and contribute to motor or procedural learning (reinforcement learning). The input stage of the basal ganglia, the striatum, is shaped by glutamatergic input from the cortex and thalamus and by the dopamine system. All intrinsic neurons of the striatum are GABAergic and inhibitory except for the cholinergic interneurons. Too little dopamine and all vertebrates show symptoms similar to that of a Parkinsonian patient, whereas too much dopamine results in hyperkinesia with involuntary movements. In this article, we discuss the detailed organization of the basal ganglia, with the different cell types, their properties, and contributions to basal ganglia functions. The striatal projection neurons represent 95% of all neurons in the striatum and are subdivided into two types, one that projects directly to the output stage, referred to as the "direct" pathway that promotes action, and the other subtype that targets the output nuclei via intercalated basal ganglia nuclei. This "indirect" pathway has an opposite effect. The striatal projection neurons express a set of ion channels that give them a high threshold for activation, whereas neurons in all other parts of the basal ganglia have a resting discharge that allows for modulation in both an increased and decreased direction.
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| 8. |
- Grillner, Sten, et al.
(author)
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Mechanisms for selection of basic motor programs : roles for the striatum and pallidum
- 2005
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In: TINS - Trends in Neurosciences. - : Elsevier BV. - 0166-2236 .- 1878-108X. ; 28:7, s. 364-370
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Research review (peer-reviewed)abstract
- The nervous system contains a toolbox of motor programs in the brainstem and spinal cord--that is, neuronal networks designed to handle the basic motor repertoire required for survival, including locomotion, posture, eye movements, breathing, chewing, swallowing and expression of emotions. The neural mechanisms responsible for selecting which motor program should be recruited at a given instant are the focus of this review. Motor programs are kept under tonic inhibition by GABAergic pallidal neurons (the output nuclei of the basal ganglia). The motor programs can be relieved from pallidal inhibition through activation of striatal neurons at the input stage of the basal ganglia. It is argued that the striatum has a prominent role in selecting which motor program should be called into action.
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| 9. |
- Grillner, Sten, et al.
(author)
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Modeling a vertebrate motor system : pattern generation, steering and control of body orientation
- 2007
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In: Progress in Brain Research. - 0079-6123 .- 1875-7855. ; 165, s. 221-234
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Research review (peer-reviewed)abstract
- The lamprey is one of the few vertebrates in which the neural control system for goal-directed locomotion including steering and control of body orientation is well described at a cellular level. In this report we review the modeling of the central pattern-generating network, which has been carried out based on detailed experimentation. In the same way the modeling of the control system for steering and control of body orientation is reviewed, including neuromechanical simulations and robotic devices.
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| 10. |
- Grillner, Sten, et al.
(author)
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Neural basis of goal-directed locomotion : An overview
- 2007
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In: Brain Research Reviews. - : Elsevier BV. - 0165-0173 .- 1872-6321. ; 57:1, s. 2-12
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Journal article (peer-reviewed)abstract
- The different neural control systems involved in goal-directed vertebrate locomotion are reviewed. They include not only the central pattern generator networks in the spinal cord that generate the basic locomotor synergy and the brainstem command systems for locomotion but also the control systems for steering and control of body orientation (posture) and finally the neural structures responsible for determining which motor programs should be turned on in a given instant. The role of the basal ganglia is considered in this context. The review summarizes the available information from a general vertebrate perspective, but specific examples are often derived from the lamprey, which provides the most detailed information when considering cellular and network perspectives.
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