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1.
  • Apps, Richard, et al. (författare)
  • Cerebellar Modules and Their Role as Operational Cerebellar Processing Units
  • 2018
  • Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4222. ; 17:5, s. 654-682
  • Tidskriftsartikel (refereegranskat)abstract
    • The compartmentalization of the cerebellum into modules is often used to discuss its function. What, exactly, can be considered a module, how do they operate, can they be subdivided and do they act individually or in concert are only some of the key questions discussed in this consensus paper. Experts studying cerebellar compartmentalization give their insights on the structure and function of cerebellar modules, with the aim of providing an up-to-date review of the extensive literature on this subject. Starting with an historical perspective indicating that the basis of the modular organization is formed by matching olivocorticonuclear connectivity, this is followed by consideration of anatomical and chemical modular boundaries, revealing a relation between anatomical, chemical, and physiological borders. In addition, the question is asked what the smallest operational unit of the cerebellum might be. Furthermore, it has become clear that chemical diversity of Purkinje cells also results in diversity of information processing between cerebellar modules. An additional important consideration is the relation between modular compartmentalization and the organization of the mossy fiber system, resulting in the concept of modular plasticity. Finally, examination of cerebellar output patterns suggesting cooperation between modules and recent work on modular aspects of emotional behavior are discussed. Despite the general consensus that the cerebellum has a modular organization, many questions remain. The authors hope that this joint review will inspire future cerebellar research so that we are better able to understand how this brain structure makes its vital contribution to behavior in its most general form.
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2.
  • Belmeguenai, Amor, et al. (författare)
  • Intrinsic Plasticity Complements Long-Term Potentiation in Parallel Fiber Input Gain Control in Cerebellar Purkinje Cells
  • 2010
  • Ingår i: The Journal of Neuroscience. - 1529-2401. ; 30:41, s. 13630-13643
  • Tidskriftsartikel (refereegranskat)abstract
    • Synaptic gain control and information storage in neural networks are mediated by alterations in synaptic transmission, such as in long-term potentiation (LTP). Here, we show using both in vitro and in vivo recordings from the rat cerebellum that tetanization protocols for the induction of LTP at parallel fiber (PF)-to-Purkinje cell synapses can also evoke increases in intrinsic excitability. This form of intrinsic plasticity shares with LTP a requirement for the activation of protein phosphatases 1, 2A, and 2B for induction. Purkinje cell intrinsic plasticity resembles CA1 hippocampal pyramidal cell intrinsic plasticity in that it requires activity of protein kinaseA (PKA) and case in kinase 2 (CK2) and is mediated by a downregulation of SK-type calcium-sensitive K conductances. In addition, Purkinje cell intrinsic plasticity similarly results in enhanced spine calcium signaling. However, there are fundamental differences: first, while in the hippocampus increases in excitability result in a higher probability for LTP induction, intrinsic plasticity in Purkinje cells lowers the probability for subsequent LTP induction. Second, intrinsic plasticity raises the spontaneous spike frequency of Purkinje cells. The latter effect does not impair tonic spike firing in the target neurons of inhibitory Purkinje cell projections in the deep cerebellar nuclei, but lowers the Purkinje cell signal-to-noise ratio, thus reducing the PF readout. These observations suggest that intrinsic plasticity accompanies LTP of active PF synapses, while it reduces at weaker, nonpotentiated synapses the probability for subsequent potentiation and lowers the impact on the Purkinje cell output.
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3.
  • Bengtsson, Fredrik, et al. (författare)
  • Climbing Fiber Coupling between Adjacent Purkinje Cell Dendrites in Vivo.
  • 2009
  • Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 3
  • Tidskriftsartikel (refereegranskat)abstract
    • Climbing fiber discharges within the rat cerebellar cortex have been shown to display synchrony, especially for climbing fibers terminating in the same parasagittal bands. In addition, Purkinje cells which have the smallest rostrocaudal separation also seem to have the highest degree of synchrony. But this has so far only been investigated for distances down to 250 mum. In the present study, we wanted to investigate whether Purkinje cells that are located immediately next to each other display a particularly pronounced synchrony in their climbing fiber discharges. To this end, we used a previously undescribed type of electrophysiological recording, a single electrode, loose patch, dual dendritic recording, from pairs of adjacent Purkinje cells in the decerebrated, non-anesthetized cat. From each recorded dendrite, this technique provided well isolated, unitary calcium spikes, which we found to have a spontaneous activity that was essentially identical with the pattern of spontaneous climbing fiber discharges. By calculating the coupling in firing between the adjacent dendrites, we found that most climbing fiber responses occurred independently of each other and that the probability of coupled discharges was less than 8%. These values are comparable to those obtained in previous studies for Purkinje cells located within the same parasagittal band and show that climbing fiber coupling within a microzone exists also in non-rodent mammalian species. However, since the degree of synchrony of climbing fiber discharge was not particularly pronounced in adjacent Purkinje cells, it seems unlikely that climbing fiber synchrony has pronounced systematic regional variations within the same microzone.
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4.
  • Bengtsson, Fredrik, et al. (författare)
  • Cross-correlations between pairs of neurons in cerebellar cortex in vivo.
  • 2013
  • Ingår i: Neural Networks. - : Elsevier BV. - 1879-2782 .- 0893-6080. ; 47:Dec.,06, s. 88-94
  • Tidskriftsartikel (refereegranskat)abstract
    • In the present paper we apply a new neurophysiological technique to make single-electrode, dual loose-patch recordings from pairs of neuronal elements in the cerebellar cortex in vivo. The analyzed cell pairs consisted of an inhibitory molecular layer interneuron and a Purkinje cell (PC) or a Golgi cell and a granule cell, respectively. To detect the magnitude of the unitary inhibitory synaptic inputs we used histograms of the spike activity of the target cell, triggered by the spikes of the inhibitory cell. Using this analysis, we found that single interneurons had no detectable effect on PC firing, which could be explained by an expected very low synaptic weight of individual interneuron-PC connections. However, interneurons did have a weak delaying effect on the overall series of interspike intervals of PCs. Due to the very high number of inhibitory synapses on each PC, a concerted activation of the interneurons could still achieve potent PC inhibition as previously shown. In contrast, in the histograms of the Golgi cell-granule cell pairs, we found a weak inhibitory effect on the granule cell but only at the time period defined as the temporal domain of the slow IPSP previously described for this connection. Surprisingly, the average granule cell firing frequency sampled at one second was strongly modulated with a negative correlation to the overall firing level of the Golgi cell when the latter was modified through current injection via the patch pipette. These findings are compatible with that tonic inhibition is the dominant form of Golgi cell-granule cell inhibition in the adult cerebellum in vivo.
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5.
  • Bengtsson, Fredrik, et al. (författare)
  • In Vivo Analysis of Inhibitory Synaptic Inputs and Rebounds in Deep Cerebellar Nuclear Neurons
  • 2011
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Neuronal function depends on the properties of the synaptic inputs the neuron receive and on its intrinsic responsive properties. However, the conditions for synaptic integration and activation of intrinsic responses may to a large extent depend on the level of background synaptic input. In this respect, the deep cerebellar nuclear (DCN) neurons are of particular interest: they feature a massive background synaptic input and an intrinsic, postinhibitory rebound depolarization with profound effects on the synaptic integration. Using in vivo whole cell patch clamp recordings from DCN cells in the cat, we find that the background of Purkinje cell input provides a tonic inhibitory synaptic noise in the DCN cell. Under these conditions, individual Purkinje cells appear to have a near negligible influence on the DCN cell and clear-cut rebounds are difficult to induce. Peripheral input that drives the simple spike output of the afferent PCs to the DCN cell generates a relatively strong DCN cell inhibition, but do not induce rebounds. In contrast, synchronized climbing fiber activation, which leads to a synchronized input from a large number of Purkinje cells, can induce profound rebound responses. In light of what is known about climbing fiber activation under behaviour, the present findings suggest that DCN cell rebound responses may be an unusual event. Our results also suggest that cortical modulation of DCN cell output require a substantial co-modulation of a large proportion of the PCs that innervate the cell, which is a possible rationale for the existence of the cerebellar microcomplex.
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6.
  • Bengtsson, Fredrik, et al. (författare)
  • Integration of sensory quanta in cuneate nucleus neurons in vivo
  • 2013
  • Ingår i: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2, s. e56630-
  • Tidskriftsartikel (refereegranskat)abstract
    • Discriminative touch relies on afferent information carried to the central nervous system by action potentials (spikes) in ensembles of primary afferents bundled in peripheral nerves. These sensory quanta are first processed by the cuneate nucleus before the afferent information is transmitted to brain networks serving specific perceptual and sensorimotor functions. Here we report data on the integration of primary afferent synaptic inputs obtained with in vivo whole cell patch clamp recordings from the neurons of this nucleus. We find that the synaptic integration in individual cuneate neurons is dominated by 4-8 primary afferent inputs with large synaptic weights. In a simulation we show that the arrangement with a low number of primary afferent inputs can maximize transfer over the cuneate nucleus of information encoded in the spatiotemporal patterns of spikes generated when a human fingertip contact objects. Hence, the observed distributions of synaptic weights support high fidelity transfer of signals from ensembles of tactile afferents. Various anatomical estimates suggest that a cuneate neuron may receive hundreds of primary afferents rather than 4-8. Therefore, we discuss the possibility that adaptation of synaptic weight distribution, possibly involving silent synapses, may function to maximize information transfer in somatosensory pathways.
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7.
  • Bengtsson, Fredrik, et al. (författare)
  • Ketamine and xylazine depress sensory-evoked parallel fiber and climbing fiber responses.
  • 2007
  • Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 98:3, s. 705-1697
  • Tidskriftsartikel (refereegranskat)abstract
    • Abstract The last few years have seen an increase in the variety of in vivo experiments used for studying cerebellar physiological mechanisms. A combination of ketamine and xylazine has become a particularly popular form of anesthesia. However, because nonanesthetized control conditions are lacking in these experiments, so far there has been no evaluation of the effects of these drugs on the physiological activity in the cerebellar neuronal network. In the present study, we used the mossy fiber, parallel fiber, and climbing fiber field potentials evoked in the nonanesthetized, decerebrated rat to serve as a control condition against which the effects of intravenous drug injections could be compared. All anesthetics were applied at doses required for normal maintenance of anesthesia. We found that ketamine substantially depressed the evoked N3 field potential, which is an indicator of the activity in the parallel fiber synapses (-40%), and nearly completely abolished evoked climbing fiber field potentials (-90%). Xylazine severely depressed the N3 field (-75%) and completely abolished the climbing fiber field (-100%). In a combination commonly used for general anesthesia (20:1), ketamine-xylazine injections also severely depressed the N3 field (-75%) and nearly completely abolished the climbing fiber field (-90%). We also observed that lowered body and surface temperatures (<34 degrees C) resulted in a substantial depression of the N3 field (-50%). These results urge for some caution in the interpretations of studies on cerebellar network physiology performed in animals anesthetized with these drugs
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8.
  • Bengtsson, Fredrik, et al. (författare)
  • Specific Relationship between Excitatory Inputs and Climbing Fiber Receptive Fields in Deep Cerebellar Nuclear Neurons.
  • 2014
  • Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1
  • Tidskriftsartikel (refereegranskat)abstract
    • Many mossy fiber pathways to the neurons of the deep cerebellar nucleus (DCN) originate from the spinal motor circuitry. For cutaneously activated spinal neurons, the receptive field is a tag indicating the specific motor function the spinal neuron has. Similarly, the climbing fiber receptive field of the DCN neuron reflects the specific motor output function of the DCN neuron. To explore the relationship between the motor information the DCN neuron receives and the output it issues, we made patch clamp recordings of DCN cell responses to tactile skin stimulation in the forelimb region of the anterior interposed nucleus in vivo. The excitatory responses were organized according to a general principle, in which the DCN cell responses became stronger the closer the skin site was located to its climbing fiber receptive field. The findings represent a novel functional principle of cerebellar connectivity, with crucial importance for our understanding of the function of the cerebellum in movement coordination.
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9.
  • Caligiore, Daniele, et al. (författare)
  • Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.
  • 2016
  • Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230.
  • Tidskriftsartikel (refereegranskat)abstract
    • Despite increasing evidence suggesting the cerebellum works in concert with the cortex and basal ganglia, the nature of the reciprocal interactions between these three brain regions remains unclear. This consensus paper gathers diverse recent views on a variety of important roles played by the cerebellum within the cerebello-basal ganglia-thalamo-cortical system across a range of motor and cognitive functions. The paper includes theoretical and empirical contributions, which cover the following topics: recent evidence supporting the dynamical interplay between cerebellum, basal ganglia, and cortical areas in humans and other animals; theoretical neuroscience perspectives and empirical evidence on the reciprocal influences between cerebellum, basal ganglia, and cortex in learning and control processes; and data suggesting possible roles of the cerebellum in basal ganglia movement disorders. Although starting from different backgrounds and dealing with different topics, all the contributors agree that viewing the cerebellum, basal ganglia, and cortex as an integrated system enables us to understand the function of these areas in radically different ways. In addition, there is unanimous consensus between the authors that future experimental and computational work is needed to understand the function of cerebellar-basal ganglia circuitry in both motor and non-motor functions. The paper reports the most advanced perspectives on the role of the cerebellum within the cerebello-basal ganglia-thalamo-cortical system and illustrates other elements of consensus as well as disagreements and open questions in the field.
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10.
  • Cenci, M. Angela, et al. (författare)
  • On the neuronal circuitry mediating l-DOPA-induced dyskinesia
  • 2018
  • Ingår i: Journal of neural transmission. - : Springer. - 0300-9564 .- 1435-1463. ; 125:8, s. 1157-1169
  • Forskningsöversikt (refereegranskat)abstract
    • With the advent of rodent models of l-DOPA-induced dyskinesia (LID), a growing literature has linked molecular changes in the striatum to the development and expression of abnormal involuntary movements. Changes in information processing at the striatal level are assumed to impact on the activity of downstream basal ganglia nuclei, which in turn influence brain-wide networks, but very little is actually known about systems-level mechanisms of dyskinesia. As an aid to approach this topic, we here review the anatomical and physiological organisation of cortico-basal ganglia-thalamocortical circuits, and the changes affecting these circuits in animal models of parkinsonism and LID. We then review recent findings indicating that an abnormal cerebellar compensation plays a causal role in LID, and that structures outside of the classical motor circuits are implicated too. In summarizing the available data, we also propose hypotheses and identify important knowledge gaps worthy of further investigation. In addition to informing novel therapeutic approaches, the study of LID can provide new clues about the interplay between different brain circuits in the control of movement.
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11.
  • Dean, Paul, et al. (författare)
  • Adaptive Filter Models
  • 2021
  • Ingår i: Handbook of the Cerebellum and Cerebellar Disorders : Second Edition: Volume 3 - Second Edition: Volume 3. - Cham : Springer International Publishing. - 9783030238100 - 9783030238094 ; , s. 1503-1514
  • Bokkapitel (refereegranskat)abstract
    • The original chapter on adaptive-filter models addressed the issue of how far such models were consistent with experimental evidence. Here we consider one particularly important kind of evidence, that concerning the nature of the synaptic plasticity that underlies cerebellar learning. The basic decorrelation learning rule employed by the adaptive-filter model can be translated into spike timing-dependent plasticity form, in which temporal coincidence of parallel fiber and climbing fiber spikes produces LTD at parallel fiber synapses on Purkinje cells, and noncoincidence produces LTP. Although this appears at first sight to be consistent with extensive evidence demonstrating the existence of LTD, other studies have raised serious issues about its functional role. For example, Schonewille et al. (Neuron 70:43-50, 2011) demonstrated that mutant mice unable to sequester Purkinje cell AMPA receptors-the mechanism thought to underlie LTD-did indeed lack LTD, but showed no evidence of impaired learning of typical “cerebellar” tasks such as adaptation of the vestibulo-ocular reflex or eyeblink conditioning. This discrepancy focusses attention on (i) the potential importance of LTP for the initial phases of cerebellar learning, and (ii) the problems posed by reliance on in vitro preparations. An important question concerning the latter is therefore whether the blockage of LTD demonstrated in the mutant mice by Schonewille et al. would also be found in vivo. Resolving this issue would clarify the role of the cerebellum in supervised learning in general, and the plausibility of adaptivefilter models in particular.
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12.
  • Dean, Paul, et al. (författare)
  • An adaptive filter model of cerebellar zone C3 as a basis for safe limb control?
  • 2013
  • Ingår i: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 591:22, s. 5459-5474
  • Forskningsöversikt (refereegranskat)abstract
    • The review asks how the adaptive filter model of the cerebellum might be relevant to experimental work on zone C3, one of the most extensively studied regions of cerebellar cortex. As far as features of the cerebellar microcircuit are concerned, the model appears to fit very well with electrophysiological discoveries concerning the importance of molecular layer interneurons and their plasticity, the significance of long-term potentiation and the striking number of silent parallel fibre synapses. Regarding external connectivity and functionality, a key feature of the adaptive filter model is its use of the decorrelation algorithm, which renders it uniquely suited to problems of sensory noise cancellation. However, this capacity can be extended to the avoidance of sensory interference, by appropriate movements of, for example, the eyes in the vestibulo-ocular reflex. Avoidance becomes particularly important when painful signals are involved, and as the climbing fibre input to zone C3 is extremely responsive to nociceptive stimuli, it is proposed that one function of this zone is the avoidance of pain by, for example, adjusting movements of the body to avoid self-harm. This hypothesis appears consistent with evidence from humans and animals concerning the role of the intermediate cerebellum in classically conditioned withdrawal reflexes, but further experiments focusing on conditioned avoidance are required to test the hypothesis more stringently. The proposed architecture may also be useful for automatic self-adjusting damage avoidance in robots, an important consideration for next generation soft' robots designed to interact with people.
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13.
  • Dean, Paul, et al. (författare)
  • The cerebellar microcircuit as an adaptive filter: experimental and computational evidence
  • 2010
  • Ingår i: Nature Reviews Neuroscience. - : Springer Science and Business Media LLC. - 1471-003X .- 1471-0048. ; 11:1, s. 30-43
  • Forskningsöversikt (refereegranskat)abstract
    • Initial investigations of the cerebellar microcircuit inspired the Marr-Albus theoretical framework of cerebellar function. We review recent developments in the experimental understanding of cerebellar microcircuit characteristics and in the computational analysis of Marr-Albus models. We conclude that many Marr-Albus models are in effect adaptive filters, and that evidence for symmetrical long-term potentiation and long-term depression, interneuron plasticity, silent parallel fibre synapses and recurrent mossy fibre connectivity is strikingly congruent with predictions from adaptive-filter models of cerebellar function. This congruence suggests that insights from adaptive-filter theory might help to address outstanding issues of cerebellar function, including both microcircuit processing and extra-cerebellar connectivity.
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14.
  • Ejserholm, Fredrik, et al. (författare)
  • A polymer based electrode array for recordings in the cerebellum
  • 2011
  • Ingår i: 2011 5th International IEEE/EMBS Conference on Neural Engineering (NER). - 9781424441402 ; , s. 376-379
  • Konferensbidrag (refereegranskat)abstract
    • A polymer foil based array with 9 gold electrodes for chronic electrophysiological recordings in the CNS has been developed. A polymer, SU-8, is pattered using photolithography techniques used every day in micro fabrication. This is beneficial if the electrode would be manufactured on a large scale basis. The technique makes it easy to adapt the array to best fit the structure of interest at the time, in this study the rat cerebellar cortex. The use of SU-8 as the base of the array makes the array very flexible, hence lets it stay close to the same cells following the movement of the brain. The electrodes can then be modified with platinum black to lower the impedance of the electrode up to one order of magnitude, making us able to create smaller electrodes but keeping the low impedance necessary to get a get the signal to noise ratio required. Platinum black modified arrays were also implanted chronically and showed excellent signal recording capabilities in rat cerebellum.
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15.
  • Ekerot, Carl-Fredrik, et al. (författare)
  • Chapter 24 The control of forelimb movements by intermediate cerebellum
  • 1997
  • Ingår i: Progress in brain research. - 0079-6123. - 0444801049 ; 114, s. 423-429
  • Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
    • In a series of studies, the functional organization of cerebellar regions contributing to the control of forelimb movements via the rubro- and corticospinal tracts has been characterized in the cat. The system consists of the cerebellar cortical C1, C3 and Y zones and their efferent intracerebellar nucleus, the interpositus anterior. Based on analyses of cutaneous and muscle afferent climbing fibre input, of corticonuclear connections and of limb movements controlled, a modular organization of this cerebellar control system is proposed. Each module consists of a number of cortical microzones, defined by their homogeneous climbing fibre input, and a group of neurones in nucleus interpositus anterior on which these microzones converge. The input to climbing fibres is multi-modal and originates from cutaneous A beta (tactile), A delta and C (nociceptive) fibres and from muscle afferents. The cutaneous receptive fields have spatial characteristics suggestive of a relation to elemental movements. For most climbing fibres, the spatial relationship between cutaneous and muscle afferent input is such that the muscle afferent input originates from muscles that, if activated, would tend to move the cutaneous receptive field of the climbing fibre towards a stimulus applied to the skin. By contrast, the limb movement controlled by the module often has the opposite direction, and would thus tend to move the cutaneous receptive field away from a stimulus applied to the skin. Functional implications of this organization for the involvement of these regions in acute and adaptive motor control of limb movements are discussed.
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16.
  • Ekerot, Carl-Fredrik, et al. (författare)
  • Functional relation between corticonuclear input and movements evoked on microstimulation in cerebellar nucleus interpositus anterior in the cat
  • 1995
  • Ingår i: Experimental Brain Research. - 0014-4819. ; 106:3, s. 365-376
  • Tidskriftsartikel (refereegranskat)abstract
    • The functional relation between receptive fields of climbing fibres projecting to the C1, C3 and Y zones and forelimb movements controlled by nucleus interpositus anterior via the rubrospinal tract were studied in cats decerebrated at the pre-collicular level. Microelectrode tracks were made through the caudal half of nucleus interpositus anterior. This part of the nucleus receives its cerebellar cortical projection from the forelimb areas of these three sagittal zones. The C3 zone has been demonstrated to consist of smaller functional units called microzones. Natural stimulation of the forelimb skin evoked positive field potentials in the nucleus. These potentials have previously been shown to be generated by climbing fibre-activated Purkinje cells and were mapped at each nuclear site, to establish the climbing fibre receptive fields of the afferent microzones. The forelimb movement evoked by microstimulation at the same site was then studied. The movement usually involved more than one limb segment. Shoulder retraction and elbow flexion were frequently evoked, whereas elbow extension was rare and shoulder protraction never observed. In total, movements at the shoulder and/or elbow occurred for 96% of the interpositus sites. At the wrist, flexion and extension movements caused by muscles with radial, central or ulnar insertions on the paw were all relatively common. Pure supination and pronation movements were also observed. Movements of the digits consisted mainly of dorsal flexion of central or ulnar digits. A comparison of climbing fibre receptive fields and associated movements for a total of 110 nuclear sites indicated a general specificity of the input-output relationship of this cerebellar control system. Several findings suggested that the movement evoked from a particular site would act to withdraw the area of the skin corresponding to the climbing fibre receptive field of the afferent microzones. For example, sites with receptive fields on the dorsum of the paw were frequently associated with palmar flexion at the wrist, whereas sites with receptive fields on the ventral side of the paw and forearm were associated with dorsiflexion at the wrist. Correspondingly, receptive fields on the lateral side of the forearm and paw were often associated with flexion at the elbow, whereas sites with receptive fields on the radial side of the forearm were associated with elbow extension. The proximal movements that were frequently observed also for distal receptive fields may serve to produce a general shortening of the limb to enhance efficiency of the withdrawal. It has previously been suggested that the cerebellar control of forelimb movements via the rubrospinal tract has a modular organisation. Each module would consist of a cell group in the nucleus interpositus anterior and its afferent microzones in the C1, C3 and Y zones, characterised by a homogenous set of climbing fibre receptive fields. The results of the present study support this organisational principle, and suggest that the efferent action of a module is to withdraw the receptive field from an external stimulus. Possible functional interpretations of the action of this system during explorative and reaching movements are discussed.
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17.
  • Ekerot, Carl-Fredrik, et al. (författare)
  • Parallel fiber receptive fields: a key to understanding cerebellar operation and learning.
  • 2003
  • Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 2:2, s. 101-109
  • Tidskriftsartikel (refereegranskat)abstract
    • In several theories of the function of the cerebellum in motor control, the mossy-fiber-parallel fiber input has been suggested to provide information used in the control of ongoing movements whereas the role of climbing fibers is to induce plastic changes of parallel fiber (PF) synapses on Purkinje cells. From studies of climbing fibers during the last few decades, we have gained detailed knowledge about the zonal and microzonal organization of the cerebellar cortex and the information carried by climbing fibers. However, properties of the PF input to Purkinje cells and inhibitory interneurones have been largely unknown. The present review, which focuses on the C3 zone of the cerebellar anterior lobe, will present and discuss recent data of the cutaneous PF input to Purkinje cells, interneurons and Golgi cells as well as novel forms of PF plasticity
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18.
  • Ekerot, Carl-Fredrik, et al. (författare)
  • Synaptic Integration in Cerebellar Granule Cells
  • 2008
  • Ingår i: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 7:4, s. 539-541
  • Tidskriftsartikel (refereegranskat)abstract
    • To understand the function of cerebellar granule cells, we need detailed knowledge about the information carried by their afferent mossy fibers and how this information is integrated by the granule cells. Recently, we made whole cell recordings from granule cells in the non-anesthetized, decerebrate cats. All recordings were made in the forelimb area of the C3 zone for which the afferent and efferent connections and functional organization have been investigated in detail. Major findings of the study were that the mossy fiber input to single granule cells was modality- and receptive field-specific and that simultaneous activity in two and usually more of the afferent mossy fibers were required to activate the granule cell spike. The high threshold for action potentials and the convergence of afferents with virtually identical information suggest that an important function of granule cells is to increase the signal-to-noise ratio of the mossy fiber-parallel fiber information. Thus a high-sensitivity, noisy mossy fiber input is transformed by the granule cell to a high-sensitivity, low-noise signal.
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19.
  • Enander, Jonas M.D., et al. (författare)
  • A model for self-organization of sensorimotor function : spinal interneuronal integration
  • 2022
  • Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 127:6, s. 1478-1495
  • Tidskriftsartikel (refereegranskat)abstract
    • Control of musculoskeletal systems depends on integration of voluntary commands and somatosensory feedback in the complex neural circuits of the spinal cord. It has been suggested that the various connectivity patterns that have been identified experimentally may result from the many transcriptional types that have been observed in spinal interneurons. We ask instead whether the muscle-specific details of observed connectivity patterns can arise as a consequence of Hebbian adaptation during early development, rather than being genetically ordained. We constructed an anatomically simplified model musculoskeletal system with realistic muscles and sensors and connected it to a recurrent, random neuronal network consisting of both excitatory and inhibitory neurons endowed with Hebbian learning rules. We then generated a wide set of randomized muscle twitches typical of those described during fetal development and allowed the network to learn. Multiple simulations consistently resulted in diverse and stable patterns of activity and connectivity that included subsets of the interneurons that were similar to “archetypical” interneurons described in the literature. We also found that such learning led to an increased degree of cooperativity between interneurons when performing larger limb movements on which it had not been trained. Hebbian learning gives rise to rich sets of diverse interneurons whose connectivity reflects the mechanical properties of the system. At least some of the transcriptomic diversity may reflect the effects of this process rather than the cause of the connectivity. Such a learning process seems better suited to respond to the musculoskeletal mutations that underlie the evolution of new species. NEW & NOTEWORTHY We present a model of a self-organizing early spinal cord circuitry, which is attached to a biologically realistic sensorized musculoskeletal system. Without any a priori-defined connectivity or organization, learning induced by spontaneous, fetal-like motor activity results in the emergence of a well-functioning spinal interneuronal circuit whose connectivity patterns resemble in many respects those observed in the adult mammalian spinal cord. Hence, our result questions the importance of genetically controlled wiring for spinal cord function.
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20.
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21.
  • Enander, Jonas M.D., et al. (författare)
  • Ubiquitous neocortical decoding of tactile input patterns
  • 2019
  • Ingår i: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 13
  • Tidskriftsartikel (refereegranskat)abstract
    • Whereas functional localization historically has been a key concept in neuroscience, direct neuronal recordings show that input of a particular modality can be recorded well outside its primary receiving areas in the neocortex. Here, we wanted to explore if such spatially unbounded inputs potentially contain any information about the quality of the input received. We utilized a recently introduced approach to study the neuronal decoding capacity at a high resolution by delivering a set of electrical, highly reproducible spatiotemporal tactile afferent activation patterns to the skin of the contralateral second digit of the forepaw of the anesthetized rat. Surprisingly, we found that neurons in all areas recorded from, across all cortical depths tested, could decode the tactile input patterns, including neurons of the primary visual cortex. Within both somatosensory and visual cortical areas, the combined decoding accuracy of a population of neurons was higher than for the best performing single neuron within the respective area. Such cooperative decoding indicates that not only did individual neurons decode the input, they also did so by generating responses with different temporal profiles compared to other neurons, which suggests that each neuron could have unique contributions to the tactile information processing. These findings suggest that tactile processing in principle could be globally distributed in the neocortex, possibly for comparison with internal expectations and disambiguation processes relying on other modalities.
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22.
  • Etemadi, Leila, et al. (författare)
  • Hippocampal output profoundly impacts the interpretation of tactile input patterns in SI cortical neurons
  • 2023
  • Ingår i: iScience. - : CELL PRESS. - 2589-0042. ; 26:6
  • Tidskriftsartikel (refereegranskat)abstract
    • Due to continuous state variations in neocortical circuits, individual somatosensory cortex (SI) neurons in vivo display a variety of intracellular responses to the exact same spatiotemporal tactile input pattern. To manipulate the internal cortical state, we here used brief electrical stimulation of the output region of the hippocampus, which preceded the delivery of specific tactile afferent input patterns to digit 2 of the anesthetized rat. We find that hippocampal output had a diversified, remarkably strong impact on the intracellular response types displayed by each neuron in the primary SI to each given tactile input pattern. Qualitatively, this impact was comparable to that previously described for cortical output, which was surprising given the widely assumed specific roles of the hippocampus, such as in cortical memory formation. The findings show that hippocampal output can profoundly impact the state-dependent interpretation of tactile inputs and hence influence perception, potentially with affective and semantic components.
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23.
  • Etemadi, Leila, et al. (författare)
  • Remote cortical perturbation dynamically changes the network solutions to given tactile inputs in neocortical neurons
  • 2022
  • Ingår i: iScience. - : Elsevier BV. - 2589-0042. ; 25:1
  • Tidskriftsartikel (refereegranskat)abstract
    • The neocortex has a globally encompassing network structure, which for each given input constrains the possible combinations of neuronal activations across it. Hence, its network contains solutions. But in addition, the cortex has an ever-changing multidimensional internal state, causing each given input to result in a wide range of specific neuronal activations. Here we use intracellular recordings in somatosensory cortex (SI) neurons of anesthetized rats to show that remote, subthreshold intracortical electrical perturbation can impact such constraints on the responses to a set of spatiotemporal tactile input patterns. Whereas each given input pattern normally induces a wide set of preferred response states, when combined with cortical perturbation response states that did not otherwise occur were induced and consequently made other response states less likely. The findings indicate that the physiological network structure can dynamically change as the state of any given cortical region changes, thereby enabling a rich, multifactorial, perceptual capability.
  •  
24.
  • Garwicz, Martin, et al. (författare)
  • Cutaneous receptive fields and topography of mossy fibres and climbing fibres projecting to cat cerebellar C3 zone
  • 1998
  • Ingår i: Journal of Physiology. - 1469-7793. ; 512:1, s. 277-293
  • Tidskriftsartikel (refereegranskat)abstract
    • 1. The topographical organization of mossy fibre input to the forelimb area of the paravermal C3 zone in cerebellar lobules IV and V was investigated in barbiturate-anaesthetized cats and compared with the previously described microzonal organization of climbing fibre input to the same part of the cortex. Recordings were made in the Purkinje cell and granule cell layers from single climbing fibre and mossy fibre units, respectively, and the organization of cutaneous receptive fields was assessed for both types of afferents. 2. Based on spatial characteristics, receptive fields of single mossy fibres could be systematized into ten classes and a total of thirty-two subclasses, mainly in accordance with a scheme previously used for classification of climbing fibres. Different mossy fibres displayed a substantial range of sensitivity to natural peripheral stimulation, responded preferentially to phasic or tonic stimuli and were activated by brushing of hairs or light tapping of the skin. 3. Overall, mossy fibres to any given microzone had receptive fields resembling the climbing fibre receptive field defining that microzone. However, compared with the climbing fibre input, the mossy fibre input had a more intricate topographical organization. Mossy fibres with very similar receptive fields projected to circumscribed cortical regions, with a specific termination not only in the mediolateral, but also in some cases in the rostrocaudal and dorsoventral, dimensions of the zone. On the other hand, mossy fibre units with non-identical, albeit usually similar, receptive fields were frequently found in the same microelectrode track.
  •  
25.
  • Garwicz, Martin, et al. (författare)
  • Functional organization of the intermediate cerebellum.
  • 1995
  • Ingår i: Alpha and Gamma Motor Systems. - Boston, MA : Springer US. - 9780306451867 - 9781461519355 ; , s. 399-402
  • Konferensbidrag (refereegranskat)abstract
    • The uniform organisation of the neuronal circuitry throughout the cerebellar cortex suggests a uniform mode of operation and thus emphasises the importance of local afferent and efferent connections in determining the function of a particular part of the cortex. Based on the organisation of these connections the cerebellar cortex of the cat is divided into about ten sagittally oriented zones (see Ito, 1984 for references). A zone is anatomically defined by its projection to a restricted part of the intracerebellar or vestibular nuclei and its climbing fibre input from a circumscribed part of the inferior olive. Some of the zones are functionally coupled in that they receive branching collaterals from common olivary neurones and in turn project to the same subdivision of the intracerebellar nuclei. Since each part of the inferior olive receives input from a specific set of spino-olivary pathways, the zones can be electrophysiologically identified by the latencies and receptive fields of climbing fibre responses evoked on peripheral stimulation. The organisation of olivary afferent and nuclear efferent connections suggests that each zone, or in some cases an ensemble of zones, controls specific motor systems.
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