1. |
- Apps, Richard, et al.
(author)
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Cerebellar Modules and Their Role as Operational Cerebellar Processing Units
- 2018
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4222. ; 17:5, s. 654-682
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Journal article (peer-reviewed)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.
(author)
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Intrinsic Plasticity Complements Long-Term Potentiation in Parallel Fiber Input Gain Control in Cerebellar Purkinje Cells
- 2010
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In: The Journal of Neuroscience. - 1529-2401. ; 30:41, s. 13630-13643
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Journal article (peer-reviewed)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.
(author)
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Climbing Fiber Coupling between Adjacent Purkinje Cell Dendrites in Vivo.
- 2009
-
In: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 3
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Journal article (peer-reviewed)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.
(author)
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Cross-correlations between pairs of neurons in cerebellar cortex in vivo.
- 2013
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In: Neural Networks. - : Elsevier BV. - 1879-2782 .- 0893-6080. ; 47:Dec.,06, s. 88-94
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Journal article (peer-reviewed)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.
(author)
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In Vivo Analysis of Inhibitory Synaptic Inputs and Rebounds in Deep Cerebellar Nuclear Neurons
- 2011
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:4
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Journal article (peer-reviewed)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.
(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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7. |
- Bengtsson, Fredrik, et al.
(author)
-
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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8. |
- Bengtsson, Fredrik, et al.
(author)
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Specific Relationship between Excitatory Inputs and Climbing Fiber Receptive Fields in Deep Cerebellar Nuclear Neurons.
- 2014
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 9:1
-
Journal article (peer-reviewed)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.
(author)
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Consensus Paper: Towards a Systems-Level View of Cerebellar Function: the Interplay Between Cerebellum, Basal Ganglia, and Cortex.
- 2016
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230.
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Journal article (peer-reviewed)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.
(author)
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On the neuronal circuitry mediating l-DOPA-induced dyskinesia
- 2018
-
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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11. |
- Dean, Paul, et al.
(author)
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Adaptive Filter Models
- 2021
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In: Handbook of the Cerebellum and Cerebellar Disorders : Second Edition: Volume 3 - Second Edition: Volume 3. - Cham : Springer International Publishing. - 9783030238100 - 9783030238094 ; , s. 1503-1514
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Book chapter (peer-reviewed)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.
(author)
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An adaptive filter model of cerebellar zone C3 as a basis for safe limb control?
- 2013
-
In: Journal of Physiology. - : Wiley. - 1469-7793 .- 0022-3751. ; 591:22, s. 5459-5474
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Research review (peer-reviewed)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.
(author)
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The cerebellar microcircuit as an adaptive filter: experimental and computational evidence
- 2010
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In: Nature Reviews Neuroscience. - : Springer Science and Business Media LLC. - 1471-003X .- 1471-0048. ; 11:1, s. 30-43
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Research review (peer-reviewed)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.
(author)
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A polymer based electrode array for recordings in the cerebellum
- 2011
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In: 2011 5th International IEEE/EMBS Conference on Neural Engineering (NER). - 9781424441402 ; , s. 376-379
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Conference paper (peer-reviewed)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.
(author)
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Chapter 24 The control of forelimb movements by intermediate cerebellum
- 1997
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In: Progress in brain research. - 0079-6123. - 0444801049 ; 114, s. 423-429
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Book chapter (other academic/artistic)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.
(author)
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Functional relation between corticonuclear input and movements evoked on microstimulation in cerebellar nucleus interpositus anterior in the cat
- 1995
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In: Experimental Brain Research. - 0014-4819. ; 106:3, s. 365-376
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Journal article (peer-reviewed)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.
(author)
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Parallel fiber receptive fields: a key to understanding cerebellar operation and learning.
- 2003
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 2:2, s. 101-109
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Journal article (peer-reviewed)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.
(author)
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Synaptic Integration in Cerebellar Granule Cells
- 2008
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In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 7:4, s. 539-541
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Journal article (peer-reviewed)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.
(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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20. |
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21. |
- Enander, Jonas M.D., et al.
(author)
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Ubiquitous neocortical decoding of tactile input patterns
- 2019
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In: Frontiers in Cellular Neuroscience. - : Frontiers Media SA. - 1662-5102. ; 13
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Journal article (peer-reviewed)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.
(author)
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Hippocampal output profoundly impacts the interpretation of tactile input patterns in SI cortical neurons
- 2023
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In: iScience. - : CELL PRESS. - 2589-0042. ; 26:6
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Journal article (peer-reviewed)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.
(author)
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Remote cortical perturbation dynamically changes the network solutions to given tactile inputs in neocortical neurons
- 2022
-
In: iScience. - : Elsevier BV. - 2589-0042. ; 25:1
-
Journal article (peer-reviewed)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.
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24. |
- Garwicz, Martin, et al.
(author)
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Cutaneous receptive fields and topography of mossy fibres and climbing fibres projecting to cat cerebellar C3 zone
- 1998
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In: Journal of Physiology. - 1469-7793. ; 512:1, s. 277-293
-
Journal article (peer-reviewed)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.
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25. |
- Garwicz, Martin, et al.
(author)
-
Functional organization of the intermediate cerebellum.
- 1995
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In: Alpha and Gamma Motor Systems. - Boston, MA : Springer US. - 9780306451867 - 9781461519355 ; , s. 399-402
-
Conference paper (peer-reviewed)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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26. |
- Garwicz, Martin, et al.
(author)
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Organizational Principles of Cerebellar Neuronal Circuitry
- 1998
-
In: News in Physiological Sciences. - 1522-161X. ; 13:1, s. 26-32
-
Journal article (peer-reviewed)abstract
- We review our recent studies of cerebellar neuronal organization, emphasizing that consideration of organizational features of cerebellar circuitry represents a necessary step toward the understanding of how the cerebellum does what it does, in terms of both its internal information processing and its interaction with other motor structures.
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27. |
- Geborek, Pontus, et al.
(author)
-
Cerebellar cortical neuron responses evoked from the spinal border cell tract.
- 2013
-
In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 7
-
Journal article (peer-reviewed)abstract
- Spinocerebellar systems are likely to be crucial for cerebellar hallmark functions such as coordination. However, in terms of cerebellar functional analyses, these are perhaps among the least explored systems. The aim of the present study is to achieve activation of a single component of the spinocerebellar systems and to explore to what extent it can influence the spike output of granule cells, Golgi cells, molecular layer (ML) interneurons (stellate and basket cells) and Purkinje cells (PCs). For this purpose, we took advantage of a unique arrangement discovered in neuroanatomical studies, in which the spinal border cell (SBC) component of the ventral spinocerebellar system was found to be the only spinocerebellar tract which ascends in the contralateral lateral funiculus (coLF) and have terminations in sublobulus C1 of the paramedian lobule in the posterior cerebellum. Using electrical stimulation of this tract, we find a subset of the cerebellar cortical neurons in this region to be moderately or powerfully activated. For example, some of our granule cells displayed high intensity responses whereas the majority of the granule cells displayed no response at all. The finding that more than half of the PCs were activated by stimulation of the SBC tract indicated that this system is capable of directly influencing cerebellar cortical output. The implications of these findings for the view of the integrative functions of the cerebellar cortex are discussed.
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28. |
- Geborek, Pontus, et al.
(author)
-
Properties of bilateral spinocerebellar activation of cerebellar cortical neurons.
- 2014
-
In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 8
-
Journal article (peer-reviewed)abstract
- We aimed to explore the cerebellar cortical inputs from two spinocerebellar pathways, the spinal border cell-component of the ventral spinocerebellar tract (SBC-VSCT) and the dorsal spinocerebellar tract (DSCT), respectively, in the sublobule C1 of the cerebellar posterior lobe. The two pathways were activated by electrical stimulation of the contralateral lateral funiculus (coLF) and the ipsilateral LF (iLF) at lower thoracic levels. Most granule cells in sublobule C1 did not respond at all but part of the granule cell population displayed high-intensity responses to either coLF or iLF stimulation. As a rule, Golgi cells and Purkinje cell simple spikes responded to input from both LFs, although Golgi cells could be more selective. In addition, a small population of granule cells responded to input from both the coLF and the iLF. However, in these cases, similarities in the temporal topography and magnitude of the responses suggested that the same axons were stimulated from the two LFs, i.e., that the axons of individual spinocerebellar neurons could be present in both funiculi. This was also confirmed for a population of spinal neurons located within known locations of SBC-VSCT neurons and dorsal horn (dh) DSCT neurons. We conclude that bilateral spinocerebellar responses can occur in cerebellar granule cells, but the VSCT and DSCT systems that provide the input can also be organized bilaterally. The implications for the traditional functional separation of VSCT and DSCT systems and the issue whether granule cells primarily integrate functionally similar information or not are discussed.
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29. |
- Geborek, Pontus, et al.
(author)
-
Stimulation within the cuneate nucleus suppresses synaptic activation of climbing fibers.
- 2013
-
In: Frontiers in Neural Circuits. - : Frontiers Media SA. - 1662-5110. ; 6:120, s. 1-9
-
Journal article (peer-reviewed)abstract
- Several lines of research have shown that the excitability of the inferior olive is suppressed during different phases of movement. A number of different structures like the cerebral cortex, the red nucleus, and the cerebellum have been suggested as candidate structures for mediating this gating. The inhibition of the responses of the inferior olivary neurons from the red nucleus has been studied extensively and anatomical studies have found specific areas within the cuneate nucleus to be target areas for projections from the magnocellular red nucleus. In addition, GABA-ergic cells projecting from the cuneate nucleus to the inferior olive have been found. We therefore tested if direct stimulation of the cuneate nucleus had inhibitory effects on a climbing fiber field response, evoked by electrical stimulation of the pyramidal tract, recorded on the surface of the cerebellum. When the pyramidal tract stimulation was preceded by weak electrical stimulation (5-20 μA) within the cuneate nucleus, the amplitude of the climbing fiber field potential was strongly suppressed (approx. 90% reduction). The time course of this suppression was similar to that found after red nucleus stimulation, with a peak suppression occurring at 70 ms after the cuneate stimulation. Application of CNQX (6-cyano-7-nitroquinoxaline-2,3-dione, disodium salt) on the cuneate nucleus blocked the suppression almost completely. We conclude that a relay through the cuneate nucleus is a possible pathway for movement-related suppression of climbing fiber excitability.
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30. |
- Genna, Clara, et al.
(author)
-
Bilateral tactile input patterns decoded at comparable levels but different time scales in neocortical neurons
- 2018
-
In: The Journal of Neuroscience. - 0270-6474. ; 38:15, s. 3669-3679
-
Journal article (peer-reviewed)abstract
- The presence of contralateral tactile input can profoundly affect ipsilateral tactile perception, and unilateral stroke in somatosensory areas can result in bilateral tactile deficits, suggesting that bilateral tactile integration is an important part of brain function. Although previous studies have shown that bilateral tactile inputs exist and that there are neural interactions between inputs from the two sides, no previous study explored to what extent the local neuronal circuitry processing contains detailed information about the nature of the tactile input from the two sides. To address this question, we used a recently introduced approach to deliver a set of electrical, reproducible, tactile afferent, spatiotemporal activation patterns, which permits a high-resolution analysis of the neuronal decoding capacity, to the skin of the second forepaw digits of the anesthetized male rat. Surprisingly, we found that individual neurons of the primary somatosensory can decode contralateral and ipsilateral input patterns to comparable extents. Although the contralateral input was stronger and more rapidly decoded, given sufficient poststimulus processing time, ipsilateral decoding levels essentially caught up to contralateral levels. Moreover, there was a weak but significant correlation for neurons with high decoding performance for contralateral tactile input to also perform well on decoding ipsilateral input. Our findings shed new light on the brain mechanisms underlying bimanual haptic integration.
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31. |
- Genna, Clara, et al.
(author)
-
Spatiotemporal Dynamics of the Cortical Responses Induced by a Prolonged Tactile Stimulation of the Human Fingertips
- 2017
-
In: Brain Topography. - : Springer Science and Business Media LLC. - 0896-0267 .- 1573-6792. ; 30:4, s. 473-485
-
Journal article (peer-reviewed)abstract
- The sense of touch is fundamental for daily behavior. The aim of this work is to understand the neural network responsible for touch processing during a prolonged tactile stimulation, delivered by means of a mechatronic platform by passively sliding a ridged surface under the subject’s fingertip while recording the electroencephalogram (EEG). We then analyzed: (i) the temporal features of the Somatosensory Evoked Potentials and their topographical distribution bilaterally across the cortex; (ii) the associated temporal modulation of the EEG frequency bands. Long-latency SEP were identified with the following physiological sequence P100—N140—P240. P100 and N140 were bilateral potentials with higher amplitude in the contralateral hemisphere and with delayed latency in the ipsilateral side. Moreover, we found a late potential elicited around 200 ms after the stimulation was stopped, which likely encoded the end of tactile input. The analysis of cortical oscillations indicated an initial increase in the power of theta band (4–7 Hz) for 500 ms after the stimulus onset followed a decrease in the power of the alpha band (8–15 Hz) that lasted for the remainder of stimulation. This decrease was prominent in the somatosensory cortex and equally distributed in both contralateral and ipsilateral hemispheres. This study shows that prolonged stimulation of the human fingertip engages the cortex in widespread bilateral processing of tactile information, with different modulations of the theta and alpha bands across time.
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32. |
- Ghazaei, Mahdi, et al.
(author)
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ORF-MOSAIC for Adaptive Control of a Biomimetic Arm
- 2011
-
In: IEEE International Conference on Robotics and Biomimetics. - 9781457721373 ; , s. 1273-1278
-
Conference paper (peer-reviewed)abstract
- This study is an attempt to take advantage of a cerebellar model to control a biomimetic arm. The cerebellar controller is a modified MOSAIC model which adaptively controls the arm. We call this model ORF-MOSAIC (Organized by Receptive Fields MOdular Selection And Identification for Control). The arm features a musculoskeletal model which is controlled through muscle activations by means of optimization techniques. With as few as 16 modules, we were able to control the arm in a workspace of 30x30 cm. The system was able to adapt to an external field as well as handling new objects despite delays. The discussion section suggests that there are similarities between the microzones in the cerebellum and the modules of this new model.
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33. |
- Gustus, Agneta, et al.
(author)
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Human hand modelling: kinematics, dynamics, applications
- 2012
-
In: Biological Cybernetics. - : Springer Science and Business Media LLC. - 1432-0770 .- 0340-1200. ; 106:11-12, s. 741-755
-
Journal article (peer-reviewed)abstract
- An overview of mathematical modelling of the human hand is given. We consider hand models from a specific background: rather than studying hands for surgical or similar goals, we target at providing a set of tools with which human grasping and manipulation capabilities can be studied, and hand functionality can be described. We do this by investigating the human hand at various levels: (1) at the level of kinematics, focussing on the movement of the bones of the hand, not taking corresponding forces into account; (2) at the musculotendon structure, i.e. by looking at the part of the hand generating the forces and thus inducing the motion; and (3) at the combination of the two, resulting in hand dynamics as well as the underlying neurocontrol. Our purpose is to not only provide the reader with an overview of current human hand modelling approaches but also to fill the gaps with recent results and data, thus allowing for an encompassing picture.
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34. |
- Hayward, Vincent, et al.
(author)
-
Spatio-temporal skin strain distributions evoke low variability spike responses in cuneate neurons
- 2014
-
In: Journal of the Royal Society Interface. - : The Royal Society. - 1742-5662 .- 1742-5689. ; 11:93
-
Journal article (peer-reviewed)abstract
- A common method to explore the somatosensory function of the brain is to relate skin stimuli to neurophysiological recordings. However, interaction with the skin involves complex mechanical effects. Variability in mechanically induced spike responses is likely to be due in part to mechanical variability of the transformation of stimuli into spiking patterns in the primary sensors located in the skin. This source of variability greatly hampers detailed investigations of the response of the brain to different types of mechanical stimuli. A novel stimulation technique designed to minimize the uncertainty in the strain distributions induced in the skin was applied to evoke responses in single neurons in the cat. We show that exposure to specific spatio-temporal stimuli induced highly reproducible spike responses in the cells of the cuneate nucleus, which represents the first stage of integration of peripheral inputs to the brain. Using precisely controlled spatio-temporal stimuli, we also show that cuneate neurons, as a whole, were selectively sensitive to the spatial and to the temporal aspects of the stimuli. We conclude that the present skin stimulation technique based on localized differential tractions greatly reduces response variability that is exogenous to the information processing of the brain and hence paves the way for substantially more detailed investigations of the brain's somatosensory system.
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35. |
- Holtzman, Tahl, et al.
(author)
-
Sensory Coding by Cerebellar Mossy Fibres through Inhibition-Driven Phase Resetting and Synchronisation
- 2011
-
In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:10
-
Journal article (peer-reviewed)abstract
- Temporal coding of spike-times using oscillatory mechanisms allied to spike-time dependent plasticity could represent a powerful mechanism for neuronal communication. However, it is unclear how temporal coding is constructed at the single neuronal level. Here we investigate a novel class of highly regular, metronome-like neurones in the rat brainstem which form a major source of cerebellar afferents. Stimulation of sensory inputs evoked brief periods of inhibition that interrupted the regular firing of these cells leading to phase-shifted spike-time advancements and delays. Alongside phase-shifting, metronome cells also behaved as band-pass filters during rhythmic sensory stimulation, with maximal spike-stimulus synchronisation at frequencies close to the idiosyncratic firing frequency of each neurone. Phase-shifting and band-pass filtering serve to temporally align ensembles of metronome cells, leading to sustained volleys of near-coincident spike-times, thereby transmitting synchronised sensory information to downstream targets in the cerebellar cortex.
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36. |
- Jaeger, Dieter, et al.
(author)
-
Computation in the Cerebellum
- 2013
-
In: Neural Networks. - : Elsevier BV. - 1879-2782 .- 0893-6080. ; 47, s. 1-2
-
Journal article (other academic/artistic)
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37. |
- Jirenhed, Dan-Anders, et al.
(author)
-
Parallel fiber and climbing fiber responses in rat cerebellar cortical neurons in vivo.
- 2013
-
In: Frontiers in Systems Neuroscience. - : Frontiers Media SA. - 1662-5137. ; 7:May,17
-
Journal article (peer-reviewed)abstract
- Over the last few years we have seen a rapidly increasing interest in the functions of the inhibitory interneurons of the cerebellar cortex. However, we still have very limited knowledge about their physiological properties in vivo. The present study provides the first description of their spontaneous firing properties and their responses to synaptic inputs under non-anesthetized conditions in the decerebrated rat in vivo. We describe the spike responses of molecular layer interneurons (MLI) in the hemispheric crus1/crus2 region and compare them with those of Purkinje cells (PCs) and Golgi cells (GCs), both with respect to spontaneous activity and responses evoked by direct electrical stimulation of parallel fibers (PFs) and climbing fibers (CFs). In agreement with previous findings in the cat, we found that the CF responses in the interneurons consisted of relatively long lasting excitatory modulations of the spike firing. In contrast, activation of PFs induced rapid but short-lasting excitatory spike responses in all types of neurons. We also explored PF input plasticity in the short-term (10 min) using combinations of PF and CF stimulation. With regard to in vivo recordings from cerebellar cortical neurons in the rat, the data presented here provide the first demonstration that PF input to PC can be potentiated using PF burst stimulation and they suggest that PF burst stimulation combined with CF input may lead to potentiation of PF inputs in MLIs. We conclude that the basic responsive properties of the cerebellar cortical neurons in the rat in vivo are similar to those observed in the cat and also that it is likely that similar mechanisms of PF input plasticity apply.
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38. |
- Jörntell, Henrik, et al.
(author)
-
Cerebellar molecular layer interneurons - computational properties and roles in learning.
- 2010
-
In: Trends in Neurosciences. - : Elsevier BV. - 1878-108X .- 0166-2236. ; 33, s. 524-532
-
Journal article (peer-reviewed)abstract
- In recent years there has been an increased interest in the function of inhibitory interneurons. In the cerebellum this interest has been paired with successes in obtaining recordings from these neurons in vivo and genetic manipulations to probe their function during behavioral tasks such as motor learning. This review focuses on a synthesis of recent findings on the computational properties that these neurons confer to the cerebellar circuitry and on their recently discovered capacity for plasticity and learning in vivo. Since the circuitry of the cerebellar cortex is relatively well-defined, the specificity with which the potential roles of these interneurons can be described will help to guide new avenues of research on the functions of interneurons in general.
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39. |
- Jörntell, Henrik
(author)
-
Cerebellar Neuronal Codes-Perspectives from Intracellular Analysis In Vivo
- 2015
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In: The Neuronal Codes of the Cerebellum. - 9780128013861 ; , s. 155-172
-
Book chapter (peer-reviewed)abstract
- An accurate interpretation of the neuronal code readouts from behavioral recordings will be possible only when there is an understanding of the connectivity structure of the network under study and the format of the input that drives the circuitry. For the cerebellar cortex, this type of knowledge is comparatively advanced and can at least in some aspects be regarded as sufficient for predicting the behavioral modulations of a single neuron. The aim of this chapter is to review the state of knowledge about cerebellar neuronal codes and to pinpoint the remaining weak spots in our knowledge that prevent us from making predictions of the cerebellar neuronal code. It is concluded that, whereas the cerebellar neuronal circuitry in itself is highly characterized, there is an urgent need for characterizing the types and ranges of encoding in the mossy fiber systems. It is also concluded that cerebellar neuronal representations can be expected to be widely distributed, and the firing of individual cerebellar neurons is likely to represent only the bits and pieces of such distributed representations.
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40. |
- Jörntell, Henrik
(author)
-
Cerebellar physiology : links between microcircuitry properties and sensorimotor functions
- 2017
-
In: Journal of Physiology. - 0022-3751. ; 595:1, s. 11-27
-
Research review (peer-reviewed)abstract
- Existing knowledge of the cerebellar microcircuitry structure and physiology allows a rather detailed description of what it in itself can and cannot do. Combined with a known mapping of different cerebellar regions to afferent systems and motor output target structures, there are several constraints that can be used to describe how specific components of the cerebellar microcircuitry may work during sensorimotor control. In fact, as described in this review, the major factor that hampers further progress in understanding cerebellar function is the limited insights into the circuitry-level function of the targeted motor output systems and the nature of the information in the mossy fiber afferents. The cerebellar circuitry in itself is here summarized as a gigantic associative memory element, primarily consisting of the parallel fiber synapses, whereas most other circuitry components, including the climbing fiber system, primarily has the role of maintaining activity balance in the intracerebellar and extracerebellar circuitry. The review explores the consistency of this novel interpretational framework with multiple diverse observations at the synaptic and microcircuitry level within the cerebellum. (Figure presented.).
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41. |
- Jörntell, Henrik
(author)
-
Cerebellar Synaptic Plasticity and the Credit Assignment Problem.
- 2016
-
In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 15:2, s. 104-111
-
Research review (peer-reviewed)abstract
- The mechanism by which a learnt synaptic weight change can contribute to learning or adaptation of brain function is a type of credit assignment problem, which is a key issue for many parts of the brain. In the cerebellum, detailed knowledge not only of the local circuitry connectivity but also of the topography of different sources of afferent/external information makes this problem particularly tractable. In addition, multiple forms of synaptic plasticity and their general rules of induction have been identified. In this review, we will discuss the possible roles of synaptic and cellular plasticity at specific locations in contributing to behavioral changes. Focus will be on the parts of the cerebellum that are devoted to limb control, which constitute a large proportion of the cortex and where the knowledge of the external connectivity is particularly well known. From this perspective, a number of sites of synaptic plasticity appear to primarily have the function of balancing the overall level of activity in the cerebellar circuitry, whereas the locations at which synaptic plasticity leads to functional changes in terms of limb control are more limited. Specifically, the postsynaptic forms of long-term potentiation (LTP) and long-term depression (LTD) at the parallel fiber synapses made on interneurons and Purkinje cells, respectively, are the types of plasticity that mediate the widest associative capacity and the tightest link between the synaptic change and the external functions that are to be controlled.
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42. |
- Jörntell, Henrik, et al.
(author)
-
Climbing Fiber Receptive Fields-Organizational and Functional Aspects and Relationship to Limb Coordination.
- 2015
-
In: Cerebellum. - : Springer Science and Business Media LLC. - 1473-4230. ; 14:3, s. 360-363
-
Research review (peer-reviewed)abstract
- Climbing fiber receptive fields are a physiological marker that have proven useful to delineate the details of the olivocerebellar circuitry. They have also proven useful as a point of reference to delineate the organization of other parts of the cerebellar circuitry. But what does the location of the climbing fiber receptive field imply and what is its relation to the presumed role of the cerebellum in coordination? Can we expect that all climbing fibers have a peripheral receptive field on the skin? In this short review, we aim to cover these issues.
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43. |
- Jörntell, Henrik, et al.
(author)
-
Electrophysiological properties of parallel fiber synapses in vivo
- 2007
-
In: Neural Synapse Research Trends. - 9781600215759 - 1600215750 ; , s. 239-252
-
Book chapter (other academic/artistic)abstract
- In vitro studies have revealed intriguing properties of parallel fiber synaptic transmisson. Most notably, these synapses have been shown to induce highly variable synaptic responses, have a pronounced paired pulse facilitation and to induce later, variable synaptic responses in their target neurons. In the present study, whole cell recordings from stellate cells and basket cells were made to evaluate the properties of parallel fiber synaptic transmission under non-anesthetized in vivo conditions in decerebrated cats. Electrical parallel fiber stimulation at threshold intensity was used to study the variability as well as the delayed activation of transmission at single parallel fiber synapses. In addition, the synaptic responses to brief manual skin stimulation, which mimicked the natural synaptic activation pattern and evoked intense spike bursts in these neurons, were analyzed to gain clues about the physiological role of these parallel fiber-specific properties. The data suggest that the high variability pronounced paired-pulse facilitation and the delayed responses reported for parallel fiber synapses in vitro are virtually non-existent in vivo.
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44. |
- Jörntell, Henrik
(author)
-
Functional Organization of Cerebellar Modules Controlling Forelimb Movements: Climbing and Mossy Fibre Input and Motor Output via the Red Nucleus and Motor Cortex
- 1997
-
Doctoral thesis (other academic/artistic)abstract
- A modular organization has recently been described for the cerebellar control system comprising the forelimb areas of the C1/C3/Y zones in the cerebellar cortex and nucleus interpositus anterior (NIA) of the cat. A module is a group of cells in NIA which receives homogenous climbing fibre input via Purkinje cells that belong to the same set of microzones in the C1/C3/Y zones. The organization of input and output of these modules was investigated in order to elucidate their specific roles in motor control. Specific convergence patterns between muscle and cutaneous afferents to climbing fibres in the C3 zone were found. Thus, in the projection of the two modalities to climbing fibres, convergence was found mainly between wrist dorsiflexor muscles and cutaneous receptive fields (cut.rfs) on the dorsal and distal ulnar parts of the forelimb, between ventral flexors and ventral cut.rfs, between triceps and proximal ulnar and dorsal cut.rfs and between biceps and proximal radial cut.rfs. Convergence between muscles acting across the same joints was extensive, whereas convergence between muscles acting across different joints was less extensive. In the C3 zone, mossy fibre units were found to terminate in cluster-like aggregates of units with mainly similar cut.rfs. Clusters were apparently larger in width than microzones and adjacent clusters overlapped considerably. Accordingly, beneath the climbing fibre microzones a heterogeneous set of mossy fibres were found but the least common denominator of their receptive fields was that they covered an area of the skin that closely corresponded to the cut.rfs of the climbing fibre microzone. The movements evoked via the rubrospinal tract by electrical microstimulation of NIA were of a multi-joint character already at threshold stimulation. At least the movement component evoked at the joint just proximal to the proximal extent of the module’s climbing fibre receptive field showed a specific relationship with the receptive field. Such movement components consisted of wrist dorsiflexion for modules with ventral cut.rfs on the paw, wrist ventral flexion for modules with dorsal cut.rfs on the paw, elbow flexion for modules with ulnar cut.rfs on the forearm and elbow extension for modules with radial cut.rfs on the forearm. The topographical organization and maximal amplitudes of the responses in the motor cortex evoked from NIA were specifically related to the cut.rfs of modules. Modules with distal radial and ventral cut.rfs had the largest projection amplitudes whereas other modules with distal cut.rfs had intermediate projections and modules with proximal ulnar and dorsal cut.rfs had only weak projections. Overall topographical differences were found for the cortical projections of these three types of modules and in addition, even fine grain differences in receptive fields between modules could be related to topographical differences in their cortical projections. Input to the motor cortex from the forelimb skin differed from that from cerebellar modules both in being located to a largely separate termination area and in having a complex pattern of temporal spread over the cortical surface. The present study above all emphasizes a high degree of connectional specificity for the cerebellar modules, indicating that they may represent the ’building blocks’ of cerebellar motor control. The organizational features found also provide new restraints on the number of conceivable ways in which the cerebellar neuronal circuitry may operate.
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45. |
- Jörntell, Henrik, et al.
(author)
-
Functional organization of climbing fibre projection to the cerebellar anterior lobe of the rat
- 2000
-
In: Journal of Physiology. - 1469-7793. ; 522:2, s. 297-309
-
Journal article (peer-reviewed)abstract
- 1. The input characteristics and distribution of climbing fibre field potentials evoked by electrical stimulation of various parts of the skin were investigated in the cerebellum of barbiturate anaesthetized rats. 2. Climbing fibre responses were recorded in sagittally oriented microelectrode tracks across the mediolateral width of the anterior lobe. Climbing fibres with similar response latencies and convergence patterns terminated in sagittal bands with widths of 0.5-1.5 mm. The principal organization of the anterior lobe with respect to input characteristics and locations of sagittal zones was similar to that in the cat and ferret. Hence, the sagittal bands in the rat were tentatively named the a, b, c1, c2 and d1 zones. 3. In contrast to the cat and ferret, the a zone of the rat was characterized by short latency ipsilateral climbing fibre input. Furthermore, it was divisible into a medial 'a1' zone with convergent, proximal input and a lateral 'ax' zone with somatotopically organized input. A forelimb area with similar location and input characteristics as the X zone of the cat was found, but it formed an integral part of the ax zone. A somatotopic organization of ipsilateral, short latency climbing fibre input was also found in the c1 zone. 4. Rostrally in the anterior lobe, climbing fibres activated at short latencies from the ipsilateral side of the body terminated in a somatotopically organized transverse band which extended from the midline to the lateral end of the anterior lobe. 5. The absence of the C3 and Y zones may be interpreted as a reflection of differences in the organization of the motor systems in the rat as compared with the cat. Skilled movements, which in the cat are controlled by the C1, C3 and Y zones via the anterior interposed nucleus, may in the rat be partly controlled by the ax zone via the rostrolateral part of the fastigial nucleus.
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46. |
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47. |
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48. |
- Jörntell, Henrik, et al.
(author)
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Mathematical Modeling of Brain Circuitry during Cerebellar Movement Control
- 2012
-
In: Biologically Inspired Robotics. ; , s. 263-276
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Book chapter (peer-reviewed)abstract
- Reconstruction of movement control properties of the brain could result in many potential advantages for application in robotics. However, a hampering factor so far has been the lack of knowledge of the structure and function of brain circuitry in vivo during movement control. Much more detailed information has recently become available for the area of the cerebellum that controls arm–hand movements. In addition to previously obtained extensive background knowledge of the overall connectivity of the controlling neuronal network, recent studies have provided detailed characterizations of local microcircuitry connectivity and physiology in vivo. In the present study, we study one component of this neuronal network, the cuneate nucleus, and characterize its mathematical properties using system identification theory. The cuneate nucleus is involved in the processing of the sensory feedback evoked by movements. As a substrate for our work, we use a characterization of incoming and outgoing signals of individual neurons during sensory activation as well as a recently obtained microcircuitry characterization for this structure. We find that system identification is a useful way to find suitable mathematical models that capture the properties and transformation capabilities of the neuronal microcircuitry that constitute the cuneate nucleus. Future work will show whether specific aspects of the mathematical properties can be ascribed to a specific microcircuitry and/or neuronal property.
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49. |
- Jörntell, Henrik, et al.
(author)
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Mathematical Modeling of Brain Circuitry during Cerebellar Movement Control
- 2009
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In: Proc. 2009 IEEE International Conference on Robotics and Biomimetics (ROBIO2009), Guilin, China, Dec 19 -23, 2009. ; , s. 98-103
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Conference paper (peer-reviewed)abstract
- Reconstruction of movement control properties of the brain could result in many potential advantages for application in robotics. However, a hampering factor so far has been the lack of knowledge of the structure and function of brain circuitry in vivo during movement control. Much more detailed information has recently become available for the area of the cerebellum that controls arm-hand movements. In addition to previously obtained extensive background knowledge of the overall connectivity of the controlling neuronal network, recent studies have provided detailed characterizations of local microcircuitry connectivity and physiology in vivo. In the present study, we study one component of this neuronal network, the cuneate nucleus, and characterize its mathematical properties using system identification theory. The cuneate nucleus is involved in the processing of the sensory feedback evoked by movements. As a substrate for our work, we use a characterization of incoming and outgoing signals of individual neurons during sensory activation as well as a recently obtained microcircuitry characterization for this structure. We find that system identification is a useful way to find suitable mathematical models that capture the properties and transformation capabilities of the neuronal microcircuitry that constitute the cuneate nucleus. Future work will show whether specific aspects of the mathematical properties can be ascribed to a specific microcircuitry and/or neuronal property.
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50. |
- Jörntell, Henrik, et al.
(author)
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Mathematical Modeling of Brain Circuitry during Cerebellar Movement Control
- 2017
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In: Biologically Inspired : Robotics - Robotics. - : CRC Press. - 9781439854884 - 9781439854976 ; , s. 263-276
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Book chapter (peer-reviewed)abstract
- Reconstruction of movement control properties of the brain could result in many potential advantages for application in robotics. However, a hampering factor so far has been the lack of knowledge of the structure and function of brain circuitry in vivo during movement control. Much more detailed information has recently become available for the area of the cerebellum that controls arm-hand movements. In addition to previously obtained extensive background knowledge of the overall connectivity of the controlling neuronal network, recent studies have provided detailed characterizations of local microcircuitry connectivity and physiology in vivo. In the present study, we study one component of this neuronal network, the cuneate nucleus, and characterize its mathematical properties using system identi cation theory. The cuneate nucleus is involved in the processing of the sensory feedback evoked by movements. As a substrate for our work, we use a characterization of incoming and outgoing signals of individual neurons during sensory activation as well as a recently obtained microcircuitry characterization for this structure. We nd that system identi cation is a useful way to nd suitable mathematical models that capture the properties and transformation capabilities of the neuronal microcircuitry that constitutes the cuneate nucleus. Future work will show whether speci c aspects of the mathematical properties can be ascribed to a speci c microcircuitry and/or neuronal property.
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