| 1. |
- Enander, Jonas M.D., et al.
(author)
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A model for self-organization of sensorimotor function : spinal interneuronal integration
- 2022
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In: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 127:6, s. 1478-1495
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Journal article (peer-reviewed)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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| 2. |
- Rongala, Udaya B., et al.
(author)
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Cuneate spiking neural network learning to classify naturalistic texture stimuli under varying sensing conditions
- 2020
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In: Neural Networks. - : Elsevier BV. - 0893-6080. ; 123, s. 273-287
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Journal article (peer-reviewed)abstract
- We implemented a functional neuronal network that was able to learn and discriminate haptic features from biomimetic tactile sensor inputs using a two-layer spiking neuron model and homeostatic synaptic learning mechanism. The first order neuron model was used to emulate biological tactile afferents and the second order neuron model was used to emulate biological cuneate neurons. We have evaluated 10 naturalistic textures using a passive touch protocol, under varying sensing conditions. Tactile sensor data acquired with five textures under five sensing conditions were used for a synaptic learning process, to tune the synaptic weights between tactile afferents and cuneate neurons. Using post-learning synaptic weights, we evaluated the individual and population cuneate neuron responses by decoding across 10 stimuli, under varying sensing conditions. This resulted in a high decoding performance. We further validated the decoding performance across stimuli, irrespective of sensing velocities using a set of 25 cuneate neuron responses. This resulted in a median decoding performance of 96% across the set of cuneate neurons. Being able to learn and perform generalized discrimination across tactile stimuli, makes this functional spiking tactile system effective and suitable for further robotic applications.
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| 3. |
- Kohler, Matthias, et al.
(author)
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Biological Data Questions the Support of the Self Inhibition Required for Pattern Generation in the Half Center Model
- 2020
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 15:9 September
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Journal article (peer-reviewed)abstract
- Locomotion control in mammals has been hypothesized to be governed by a central pattern generator (CPG) located in the circuitry of the spinal cord. The most common model of the CPG is the half center model, where two pools of neurons generate alternating, oscillatory activity. In this model, the pools reciprocally inhibit each other ensuring alternating activity. There is experimental support for reciprocal inhibition. However another crucial part of the half center model is a self inhibitory mechanism which prevents the neurons of each individual pool from infinite firing. Self-inhibition is hence necessary to obtain alternating activity. But critical parts of the experimental bases for the proposed mechanisms for self-inhibition were obtained in vitro, in preparations of juvenile animals. The commonly used adaptation of spike firing does not appear to be present in adult animals in vivo. We therefore modeled several possible self inhibitory mechanisms for locomotor control. Based on currently published data, previously proposed hypotheses of the self inhibitory mechanism, necessary to support the CPG hypothesis, seems to be put into question by functional evaluation tests or by in vivo data. This opens for alternative explanations of how locomotion activity patterns in the adult mammal could be generated.
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| 4. |
- Kohler, Matthias, et al.
(author)
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The Bcm rule allows a spinal cord model to learn rhythmic movements
- 2023
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In: Biological Cybernetics. - 0340-1200. ; 117:4-5, s. 275-284
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Journal article (peer-reviewed)abstract
- Currently, it is accepted that animal locomotion is controlled by a central pattern generator in the spinal cord. Experiments and models show that rhythm generating neurons and genetically determined network properties could sustain oscillatory output activity suitable for locomotion. However, current central pattern generator models do not explain how a spinal cord circuitry, which has the same basic genetic plan across species, can adapt to control the different biomechanical properties and locomotion patterns existing in these species. Here we demonstrate that rhythmic and alternating movements in pendulum models can be learned by a monolayer spinal cord circuitry model using the Bienenstock–Cooper–Munro learning rule, which has been previously proposed to explain learning in the visual cortex. These results provide an alternative theory to central pattern generator models, because rhythm generating neurons and genetically defined connectivity are not required in our model. Though our results are not in contradiction to current models, as existing neural mechanism and structures, not used in our model, can be expected to facilitate the kind of learning demonstrated here. Therefore, our model could be used to augment existing models.
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| 5. |
- Bengtsson, Fredrik, et al.
(author)
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Ketamine and xylazine depress sensory-evoked parallel fiber and climbing fiber responses.
- 2007
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In: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 98:3, s. 705-1697
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Journal article (peer-reviewed)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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| 6. |
- Thelin, Jonas, et al.
(author)
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Implant size and fixation mode strongly influence tissue reactions in the CNS
- 2011
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:1, s. e16267-
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Journal article (peer-reviewed)abstract
- The function of chronic brain machine interfaces depends on stable electrical contact between neurons and electrodes. A key step in the development of interfaces is therefore to identify implant configurations that minimize adverse long-term tissue reactions. To this end, we here characterized the separate and combined effects of implant size and fixation mode at 6 and 12 weeks post implantation in rat (n = 24) cerebral cortex. Neurons and activated microglia and astrocytes were visualized using NeuN, ED1 and GFAP immunofluorescence microscopy, respectively. The contributions of individual experimental variables to the tissue response were quantified. Implants tethered to the skull caused larger tissue reactions than un-tethered implants. Small diameter (50 mu m) implants elicited smaller tissue reactions and resulted in the survival of larger numbers of neurons than did large diameter (200 mu m) implants. In addition, tethering resulted in an oval-shaped cavity, with a cross-section area larger than that of the implant itself, and in marked changes in morphology and organization of neurons in the region closest to the tissue interface. Most importantly, for implants that were both large diameter and tethered, glia activation was still ongoing 12 weeks after implantation, as indicated by an increase in GFAP staining between week 6 and 12, while this pattern was not observed for un-tethered, small diameter implants. Our findings therefore clearly indicate that the combined small diameter, un-tethered implants cause the smallest tissue reactions.
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| 7. |
- Nilsson, Martin, et al.
(author)
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Channel current fluctuations conclusively explain neuronal encoding of internal potential into spike trains
- 2021
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In: Physical review. E. - : American Physical Society. - 2470-0045 .- 2470-0053. ; 103:2
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Journal article (peer-reviewed)abstract
- Hodgkin and Huxley's seminal neuron model describes the propagation of voltage spikes in axons, but it cannot explain certain full-neuron features crucial for understanding the neural code. We consider channel current fluctuations in a trisection of the Hodgkin-Huxley model, allowing an analytic-mechanistic explanation of these features and yielding consistently excellent matches with in vivo recordings of cerebellar Purkinje neurons, which we use as model systems. This shows that the neuronal encoding is described conclusively by a soft-thresholding function having just three parameters. © 2021 authors. Published by the American Physical Society. Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article's title, journal citation, and DOI.
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| 8. |
- Bengtsson, Fredrik, et al.
(author)
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Integration of sensory quanta in cuneate nucleus neurons in vivo
- 2013
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 8:2, s. e56630-
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Journal article (peer-reviewed)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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| 9. |
- Kohler, Matthias, et al.
(author)
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Diversified physiological sensory input connectivity questions the existence of distinct classes of spinal interneurons
- 2022
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In: iScience. - : Elsevier BV. - 2589-0042. ; 25:4
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Journal article (peer-reviewed)abstract
- The spinal cord is engaged in all forms of motor performance but its functions are far from understood. Because network connectivity defines function, we explored the connectivity of muscular, tendon, and tactile sensory inputs among a wide population of spinal interneurons in the lower cervical segments. Using low noise intracellular whole cell recordings in the decerebrated, non-anesthetized cat in vivo, we could define mono-, di-, and trisynaptic inputs as well as the weights of each input. Whereas each neuron had a highly specific input, and each indirect input could moreover be explained by inputs in other recorded neurons, we unexpectedly also found the input connectivity of the spinal interneuron population to form a continuum. Our data hence contrasts with the currently widespread notion of distinct classes of interneurons. We argue that this suggested diversified physiological connectivity, which likely requires a major component of circuitry learning, implies a more flexible functionality.
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| 10. |
- Cenci, M. Angela, et al.
(author)
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On the neuronal circuitry mediating l-DOPA-induced dyskinesia
- 2018
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In: Journal of neural transmission. - : Springer. - 0300-9564 .- 1435-1463. ; 125:8, s. 1157-1169
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Research review (peer-reviewed)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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