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  • 1.
    Alstermark, Bror
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Ekerot, Carl-Fredrik
    Department of Experimental Medical Sciences, Section for Neuroscience, Lund.
    The lateral reticular nucleus: a precerebellar centre providing the cerebellum with overview and integration of motor functions at systems level. A new hypothesis.2013In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 591, no 22, p. 5453-5458Article in journal (Refereed)
    Abstract [en]

    The lateral reticular nucleus (LRN) is a major precerebellar centre of mossy fibre information to the cerebellum from the spinal cord that is distinct from the direct spinocerebellar paths. The LRN has traditionally been considered to provide the cerebellum with segregated information from several spinal systems controlling posture, reaching, grasping, locomotion, scratching and respiration. However, results are presented that show extensive convergence on a majority of LRN neurons from spinal systems. We propose a new hypothesis suggesting that the LRN may use extensive convergence from the different input systems to provide overview and integration of linked motor components to the cerebellum. This integrated information is sent in parallel with the segregated information from the individual systems to the cerebellum that finally may compare the activity and make necessary adjustments of various motor behaviours.

  • 2. Druzin, M
    et al.
    Haage, D
    Malinina, Evgenya
    Johansson, S
    Dual and opposing roles of presynaptic Ca2+ influx for spontaneous GABA release from rat medial preoptic nerve terminals2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 542, no 1, p. 131-146Article in journal (Refereed)
  • 3.
    Druzin, Michael
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Haage, David
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Malinina, Evgenya
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Johansson, Staffan
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Dual and opposing roles of presynaptic Ca2+ influx for spontaneous GABA release from rat medial preoptic nerve terminals.2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 542, no Pt 1, p. 131-46Article in journal (Refereed)
    Abstract [en]

    Calcium influx into the presynaptic nerve terminal is well established as a trigger signal for transmitter release by exocytosis. By studying dissociated preoptic neurons with functional adhering nerve terminals, we here show that presynaptic Ca2+ influx plays dual and opposing roles in the control of spontaneous transmitter release. Thus, application of various Ca2+ channel blockers paradoxically increased the frequency of spontaneous (miniature) inhibitory GABA-mediated postsynaptic currents (mIPSCs). Similar effects on mIPSC frequency were recorded upon washout of Cd2+ or EGTA from the external solution. The results are explained by a model with parallel Ca2+ influx through channels coupled to the exocytotic machinery and through channels coupled to Ca2+-activated K+ channels at a distance from the release site.

  • 4.
    Edin, Benoni B
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Cutaneous afferents provide information about knee joint movements in humans.2001In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 531, no Pt 1, p. 289-297Article in journal (Refereed)
    Abstract [en]

    1. Neurophysiological evidence that afferent information from skin receptors is important for proprioception has been gathered mainly in experiments relating to the human hand and finger joints. To investigate if proprioceptive information is also provided by skin mechanoreceptor afferents from skin areas related to large joints of postural importance, microneurography recordings were obtained in humans from skin afferents in the lateral cutaneous femoral nerve to study their responses to knee joint movements. 2. Data were collected from 60 sequentially recorded afferents from slowly (n = 23) and fast (n = 6) adapting low-threshold mechanoreceptors, hair follicle receptors (n = 24), field receptors (n = 1) and C mechanoreceptors (n = 6). Fascicular recordings showed that the lateral cutaneous femoral nerve supplies extensive areas of the thigh: from 5-10 cm below the inguinal ligament down to below and lateral to the knee joint; accordingly, the afferents originated in receptors located in wide areas of the human thigh. 3. All afferents from fast and slowly adapting low-threshold mechanoreceptors, as well as C mechanoreceptors, responded to manually applied skin stretch. In contrast, the same stimulus elicited, at most, feeble responses in hair follicle receptors. 4. Qualitative and quantitative analyses of the responses of a subset of afferents revealed that in particular slowly adapting afferents effectively encode both static and dynamic aspects of passively imposed knee joint movements. 5. It was concluded that receptors in the hairy skin of humans can provide high-fidelity information about knee joint movements. A previously undefined type of slowly adapting receptor (SA III) seemed particularly suited for this task whereas this does not seem to be the case for either hair follicle receptors or C mechanoreceptors.

  • 5.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Niclas
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Skin strain patterns provide kinaesthetic information to the human central nervous system.1995In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 487, no 1, p. 243-251Article in journal (Refereed)
    Abstract [en]

    1. We investigated the contribution of skin strain-related sensory inputs to movement perception and execution in five normal volunteers. The dorsal and palmar skin of the middle phalanx and the proximal interphalangeal (PIP) joint were manipulated to generate specific strain patterns in the proximal part of the index finger. To mask sensations directly related to this manipulation, skin and deeper tissues were blocked distal to the mid-portion of the proximal phalanx of the index finger by local anaesthesia. 2. Subjects were asked to move their normal right index finger either to mimic any perceived movements of the anaesthetized finger or to touch the tip of the insentient finger. 3. All subjects readily reproduced actual movements induced by the experimenter at the anaesthetized PIP joint. However, all subjects also generated flexion movements when the experimenter did not induce actual movement but produced deformations in the sentient proximal skin that were similar to those observed during actual PIP joint flexion. Likewise, the subjects indicated extension movement at the PIP joint when strain patterns corresponding to extension movements were induced. 4. In contrast, when the skin strain in the proximal part of the index finger was damped by a ring applied just proximal to the PIP joint within the anaesthetized skin area, both tested subjects failed to perceive PIP movements that actually took place.(ABSTRACT TRUNCATED AT 250 WORDS)

  • 6.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Vallbo, A B
    Stretch sensitization of human muscle spindles.1988In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 400, p. 101-11Article in journal (Refereed)
    Abstract [en]

    1. Sixty-seven afferents from the finger extensor muscles were consecutively recorded by microneurography. 2. The units were classified as primary or secondary muscle spindle afferents or Golgi tendon organ afferents on the basis of their responses to ramp-and-hold stretches, sinusoidals superimposed on ramp-and-hold stretches, maximal twitch contractions and isometric contractions and relaxations. 3. The muscle was repeatedly stretched and then either kept short or long for a few seconds followed by a slow ramp stretch. The responses of the muscle afferents to the slow stretch were compared under the two conditions. 4. Thirty out of thirty-eight units classified as primary spindle afferents and four out of eleven units classified as secondary afferents showed an enhanced response to the slow ramp when the muscle had been kept short compared to the response when the muscle had been kept long. 5. None of the eighteen Golgi tendon organ afferents showed any difference in this respect. 6. It is concluded that stretch sensitization does occur in human muscle spindles and, when present, constitutes firm evidence of the afferent originating from a muscle spindle rather than a Golgi tendon organ. In addition, due to differences in the response characteristics of primaries and secondaries, the test may aid in separating muscle spindle primary afferents from secondary afferents.

  • 7.
    Edin, Benoni B
    et al.
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Westling, Göran
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Johansson, Roland S
    Umeå University, Faculty of Medicine, Integrative Medical Biology, Physiology.
    Independent control of human finger-tip forces at individual digits during precision lifting.1992In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 450, p. 547-64Article in journal (Refereed)
    Abstract [en]

    1. Subjects lifted an object with two parallel vertical grip surfaces and a low centre of gravity using the precision grip between the tips of the thumb and index finger. The friction between the object and the digits was varied independently at each digit by changing the contact surfaces between lifts. 2. With equal frictional conditions at the two grip surfaces, the finger-tip forces were about equal at the two digits, i.e. similar vertical lifting forces and grip forces were used. With different frictions, the digit touching the most slippery surface exerted less vertical lifting force than the digit in contact with the rougher surface. Thus, the safety margins against slips were similar at the two digits whether they made contact with surfaces of similar or different friction. 3. During digital nerve block, large and variable safety margins were employed, i.e. the finger-tip forces did not reflect the surface conditions. Slips occurred more frequently than under normal conditions (14% of all trials with nerve block, <5% during normal conditions), and they only occasionally elicited compensatory adjustments of the finger-tip forces and then at prolonged latencies. 4. The partitioning of the vertical lifting force between the digits was thus dependent on digital afferent inputs and resulted from active automatic regulation and not just from the mechanics of the task. 5. The safety margin employed at a particular digit was mainly determined by the frictional conditions encountered by the digit, and to a lesser degree by the surface condition at the same digit in the previous lift (anticipatory control), but was barely influenced by the surface condition at the other digit. 6. It was concluded that the finger-tip forces were independently controlled for each digit according to a 'non-slip strategy'. The findings suggest that the force distribution among the digits represents a digit-specific lower-level neural control establishing a stable grasp. This control relies on digit-specific afferent inputs and somatosensory memory information. It is apparently subordinated to a higher-level control that is related to the total vertical lifting and normal forces required by the lifting task and the relevant physical properties of the manipulated object.

  • 8.
    Kalezic, Ivana
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Bugaychenko, Larisa A.
    Department of Movement Physiology, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev, Ukraine.
    Kostyukov, Alexander I.
    Department of Movement Physiology, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev, Ukraine.
    Pilyavskii, Alexander I.
    Department of Movement Physiology, Bogomoletz Institute of Physiology, National Academy of Sciences, Kiev, Ukraine.
    Ljubisavljevic, Milos
    Department of Neurophysiology, Institute for Medical Research, Belgrade, Serbia and Montenegro.
    Windhorst, Uwe
    Centre for Musculoskeletal Research, University of Gävle.
    Johansson, Håkan
    Centre for Musculoskeletal Research, University of Gävle.
    Fatigue-related depression of the feline monosynaptic gastrocnemius-soleus reflex2004In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 556, no 1, p. 293-296Article in journal (Refereed)
    Abstract [en]

    In decerebrate cats, changes in the monosynaptic reflex (MSR) of gastrocnemius-soleus (G-S) motoneurones were studied after fatiguing stimulation (FST) of the G-S muscles. Monosynaptic reflexes were evoked by stimulation of Ia fibres in the G-S nerve and recorded from a filament of ventral root (VR) L7. FST (intermittent 40 s(-1) stimulation for 10-12 min) was applied to the distal part of the cut VR S1. FST reduced MSR amplitudes to 0.64 +/- 0.04 (mean +/-s.e.m.) of the prefatigue values. The suppression remained stable for approximately 25 min and then MSR amplitudes gradually returned towards the normal. To test for the involvement of presynaptic and recurrent inhibition, MSRs were conditioned by stimulation of the nerve to the posterior biceps and semitendinosus (PBSt) muscles or a filament of VR L7, respectively. The intensity of presynaptic inhibition (reduction of the normalized value of MSR amplitude during conditioning) increased from 0.19 +/- 0.02 in prefatigue to 0.44 +/- 0.04 within a 5.3-18.2 min interval after FST, followed by a recovery. In contrast, the intensity of recurrent inhibition first diminished from 0.23 +/- 0.02 in prefatigue to 0.15 +/- 0.01 within 15.6-30.1 min after FST and then gradually recovered. Both primary afferent depolarization and the intensity of antidromic discharges in primary afferents increased with the presynaptic inhibition intensity. These results demonstrate a fatigue-related suppression of Ia excitation of synergistic motoneurones, probably arising from the activation of group III and IV afferents. The effects could in part be due to increased presynaptic inhibition, while recurrent inhibition plays a minor role.

  • 9.
    Kokinovic, Bojana
    et al.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology. epartment of Neuroscience and Brain Technologies (NBT), Italian Institute of Technology (IIT), Genova, Italy.
    Medini, Paolo
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB), Physiology.
    Loss of GABAB-mediated interhemispheric synaptic inhibition in stroke periphery2018In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 596, no 10, p. 1949-1964Article in journal (Refereed)
    Abstract [en]

    Recovery after stroke is mediated by plastic changes largely occurring in the lesion periphery. However, little is known about the microcircuit changes underlying recovery, the extent to which perilesional plasticity occurs at synaptic input vs. spike output level, and the connectivity behind such synaptic plasticity. We combined intrinsic imaging with extracellular and intracellular recordings and pharmacological inactivation in a focal stroke in mouse somatosensory cortex (S1). In vivo whole-cell recordings in hindlimb S1 (hS1) showed synaptic responses also to forelimb stimulation in controls, and such responses were abolished by stroke in the neighbouring forelimb area (fS1), suggesting that, under normal conditions, they originate via horizontal connections from the neighbouring fS1. Synaptic and spike responses to forelimb stimulation in hS1 recovered to quasi-normal levels 2weeks after stroke, without changes in intrinsic excitability and hindlimb-evoked spike responses. Recovered synaptic responses had longer latencies, suggesting a long-range origin of the recovery, prompting us to investigate the role of callosal inputs in the recovery process. Contralesional S1 silencing unmasked significantly larger responses to both limbs in controls, a phenomenon that was not observed when GABAB receptors were antagonized in the recorded area. Conversely, such GABAB-mediated interhemispheric inhibition was not detectable after stroke: callosal input silencing failed to change hindlimb responses, whereas it robustly reduced recovered forelimb responses. Thus, recovery of subthreshold responsiveness in the stroke periphery is accompanied by a loss of interhemispheric inhibition and this is a result of pathway-specific facilitatory action on the affected sensory response from the contralateral cortex.

  • 10. Sahlin, Kent
    et al.
    Fernström, Maria
    Svensson, Michael
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Tonkonogi, Michail
    No evidence of an intracellular lactate shuttle in rat skeletal muscle.2002In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 541, no Pt 2, p. 569-74Article in journal (Refereed)
    Abstract [en]

    The concerted view is that cytosolic pyruvate is transferred into mitochondria and after oxidative decarboxylation further metabolized in the tricarboxylic acid cycle. Recently this view has been challenged. Based on experimental evidence from rat skeletal muscle it has been concluded that mitochondria predominantly oxidize lactate in vivo and that this constitutes part of an 'intracellular lactate shuttle'. This view appears to be gaining acceptance in the scientific community and due to its conceptual importance, confirmation by independent experiments is required. We have repeated the experiments in mitochondria isolated from rat soleus muscle. Contrary to the previously published findings we cannot find any mitochondrial respiration with lactate. Analysis of lactate dehydrogenase (LDH) by spectrophotometry demonstrated that the activity in the mitochondrial fraction was only 0.7 % of total activity. However, even when external LDH was added to mitochondria, there were no signs of respiration with lactate. In the presence of conditions where lactate is converted to pyruvate (external additions of both LDH and NAD(+)), mitochondrial oxygen consumption increased. Furthermore, we provide theoretical evidence that direct mitochondrial lactate oxidation is energetically unlikely. Based on the present data we conclude that direct mitochondrial lactate oxidation does not occur in skeletal muscle. The presence of an 'intracellular lactate shuttle' can therefore be questioned.

  • 11. Sjåland, Cecilie
    et al.
    Lunde, Per Kristian
    Swift, Fredrik
    Munkvik, Morten
    Ericsson, Madelene
    Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
    Lunde, Marianne
    Boye, Sigurd
    Christensen, Geir
    Ellingsen, Øyvind
    Sejersted, Ole M
    Andersson, Kristin B
    Slowed relaxation and preserved maximal force in soleus muscles of mice with targeted disruption of the Serca2 gene in skeletal muscle2011In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 589, no Pt 24, p. 6139-6155Article in journal (Refereed)
    Abstract [en]

    Sarcoplasmic reticulum Ca(2+) ATPases (SERCAs) play a major role in muscle contractility by pumping Ca(2+) from the cytosol into the sarcoplasmic reticulum (SR) Ca(2+) store, allowing muscle relaxation and refilling of the SR with releasable Ca(2+). Decreased SERCA function has been shown to result in impaired muscle function and disease in human and animal models. In this study, we present a new mouse model with targeted disruption of the Serca2 gene in skeletal muscle (skKO) to investigate the functional consequences of reduced SERCA2 expression in skeletal muscle. SkKO mice were viable and basic muscle structure was intact. SERCA2 abundance was reduced in multiple muscles, and by as much as 95% in soleus muscle, having the highest content of slow-twitch fibres (40%). The Ca(2+) uptake rate was significantly reduced in SR vesicles in total homogenates. We did not find any compensatory increase in SERCA1 or SERCA3 abundance, or altered expression of several other Ca(2+)-handling proteins. Ultrastructural analysis revealed generally well-preserved muscle morphology, but a reduced volume of the longitudinal SR. In contracting soleus muscle in vitro preparations, skKO muscles were able to fully relax, but with a significantly slowed relaxation time compared to controls. Surprisingly, the maximal force and contraction rate were preserved, suggesting that skKO slow-twitch fibres may be able to contribute to the total muscle force despite loss of SERCA2 protein. Thus it is possible that SERCA-independent mechanisms can contribute to muscle contractile function.

  • 12. Tonkonogi, M
    et al.
    Walsh, B
    Svensson, M
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Sports Medicine.
    Sahlin, K
    Mitochondrial function and antioxidative defence in human muscle: effects of endurance training and oxidative stress.2000In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 528 Pt 2, p. 379-88Article in journal (Refereed)
    Abstract [en]

    The influence of endurance training on oxidative phosphorylation and the susceptibility of mitochondrial oxidative function to reactive oxygen species (ROS) was investigated in skeletal muscle of four men and four women. Mitochondria were isolated from muscle biopsies taken before and after 6 weeks of endurance training. Mitochondrial respiration was measured before and after exposure of mitochondria to exogenous ROS (H2O2 + FeCl2). Endurance training increased peak pulmonary O2 uptake (VO2,peak) by 24 % and maximal ADP-stimulated mitochondrial oxygen consumption (state 3) by 40% (P<0.05). Respiration in the absence of ADP (state 4), the respiratory control ratio (RCR = state 3/state 4) and the ratio between added ADP and consumed oxygen (P/O) remained unchanged by the training programme. Exposure to ROS reduced state 3 respiration but the effect was not significantly different between pre- and post-training samples. State 4 oxygen consumption increased after exposure to ROS both before (+189 %, P< 0.05) and after training (+243 %, P<0.05) and the effect was significantly higher after training (P<0.05, pre- vs. post-training). The augmented state 4 respiration could in part be attenuated by atractyloside, which indicates that ADP/ATP translocase was affected by ROS. The P/O ratio in ROS-treated mitochondria was significantly lower (P<0.05) compared to control conditions, both before (-18.6+/-2.2 %) and after training (-18.5+/-1.1%). Muscle activities of superoxide dismutase (mitochondrial and cytosolic), glutathione peroxidase and muscle glutathione status were unaffected by training. There was a positive correlation between muscle superoxide dismutase activity and age (r = 0.75; P<0.05; range of age 20-37 years), which may reflect an adaptation to increased generation of ROS in senescent muscle. The muscle glutathione pool was more reduced in subjects with high activity of glutathione peroxidase (r = 0.81; P<0.05). The influence of short-term training on mitochondrial oxygen consumption has for the first time been investigated in human skeletal muscle. The results showed that maximal mitochondrial oxidative power is increased after endurance training but that the efficiency of energy transfer (P/O ratio) remained unchanged. Antioxidative defence was unchanged after training when expressed relative to muscle weight. Although this corresponds to a reduced antioxidant protection per individual mitochondrion, the sensitivity of aerobic energy transfer to ROS was unchanged. However, the augmented ROS-induced non-coupled respiration after training indicates an increased susceptibility of mitochondrial membrane proton conductance to oxidative stress.

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