umu.sePublications
Change search
Link to record
Permanent link

Direct link
BETA
Alstermark, Bror
Publications (10 of 26) Show all publications
Jiang, J. & Alstermark, B. (2017). Dysfunctional cortico-reticulospinal and propriospinal systems may lead to impaired skilled forelimb reaching in EphA4-knockout mice. Acta Physiologica, 219, 34-35
Open this publication in new window or tab >>Dysfunctional cortico-reticulospinal and propriospinal systems may lead to impaired skilled forelimb reaching in EphA4-knockout mice
2017 (English)In: Acta Physiologica, ISSN 1748-1708, E-ISSN 1748-1716, Vol. 219, p. 34-35Article in journal, Meeting abstract (Refereed) Published
Place, publisher, year, edition, pages
WILEY-BLACKWELL, 2017
National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-132810 (URN)000393916600073 ()
Note

Supplement: S710, Meeting Abstract: P-48

Available from: 2017-05-05 Created: 2017-05-05 Last updated: 2018-06-09Bibliographically approved
Jiang, J., Azim, E., Ekerot, C.-F. & Alstermark, B. (2015). Direct and indirect spino-cerebellar pathways: shared ideas but different functions in motor control. Frontiers in Computational Neuroscience, 9, Article ID 75.
Open this publication in new window or tab >>Direct and indirect spino-cerebellar pathways: shared ideas but different functions in motor control
2015 (English)In: Frontiers in Computational Neuroscience, ISSN 1662-5188, E-ISSN 1662-5188, Vol. 9, article id 75Article in journal (Refereed) Published
Abstract [en]

The impressive precision of mammalian limb movements relies on internal feedback pathways that convey information about ongoing motor output to cerebellar circuits. The spino-cerebellar tracts (SCT) in the cervical, thoracic and lumbar spinal cord have long been considered canonical neural substrates for the conveyance of internal feedback signals. Here we consider the distinct features of an indirect spino-cerebellar route, via the brainstem lateral reticular nucleus (LRN), and the implications of this pre-cerebellar "detour" for the execution and evolution of limb motor control. Both direct and indirect spino-cerebellar pathways signal spinal interneuronal activity to the cerebellum during movements, but evidence suggests that direct SCT neurons are mainly modulated by rhythmic activity, whereas the LRN also receives information from systems active during postural adjustment, reaching and grasping. Thus, while direct and indirect spinocerebellar circuits can both be regarded as internal copy pathways, it seems likely that the direct system is principally dedicated to rhythmic motor acts like locomotion, while the indirect system also provides a means of pre-cerebellar integration relevant to the execution and coordination of dexterous limb movements.

Place, publisher, year, edition, pages
Frontiers Media, 2015
Keywords
lateral reticular nucleus (LRN), spino-cerebellar pathways, spino-LRN-cerebellar pathways, internal edback, motor control
National Category
Neurosciences Bioinformatics (Computational Biology)
Identifiers
urn:nbn:se:umu:diva-107302 (URN)10.3389/fncom.2015.00075 (DOI)000358731000001 ()26217214 (PubMedID)
Available from: 2015-08-24 Created: 2015-08-21 Last updated: 2018-06-07Bibliographically approved
Jiang, J. & Alstermark, B. (2015). Not GABA But Glycine Mediates Segmental, Propriospinal, and Bulbospinal Postsynaptic Inhibition in Adult Mouse Spinal Forelimb Motor Neurons. Journal of Neuroscience, 35(5), 1991-1998
Open this publication in new window or tab >>Not GABA But Glycine Mediates Segmental, Propriospinal, and Bulbospinal Postsynaptic Inhibition in Adult Mouse Spinal Forelimb Motor Neurons
2015 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 35, no 5, p. 1991-1998Article in journal (Refereed) Published
Abstract [en]

The general view is that both glycine (Eccles, 1964) and GABA (Curtis and Felix, 1971) evoke postsynaptic inhibition in spinal motor neurons. In newborn or juvenile animals, there are conflicting results showing postsynaptic inhibition in motor neurons by corelease of GABA and glycine (Jonas et al., 1998) or by glycine alone (Bhumbra et al., 2012). To resolve the relative contributions of GABA and glycine to postsynaptic inhibition, we performed in vivo intracellular recordings from forelimb motor neurons in adult mice. Postsynaptic potentials evoked from segmental, propriospinal, and bulbospinal systems in motor neurons were compared across four different conditions: control, after gabazine, gabazine followed by strychnine, and strychnine alone. No significant differences were observed in the proportion of IPSPs and EPSPs between control and gabazine conditions. In contrast, EPSPs but not IPSPs were recorded after adding strychnine with gabazine or administering strychnine alone, suggesting an exclusive role for glycine in postsynaptic inhibition. To test whether the injected (intraperitoneal) dose of gabazine blocked GABAergic inhibitory transmission, we evoked GABA(A) receptor-mediated monosynaptic IPSPs in deep cerebellar nuclei neurons by stimulation of Purkinje cell fibers. No monosynaptic IPSPs could be recorded in the presence of gabazine, showing the efficacy of gabazine treatment. Our results demonstrate that, in the intact adult mouse, the postsynaptic inhibitory effects in spinal motor neurons exerted by three different systems, intrasegmental and intersegmental as well as supraspinal, are exclusively glycinergic. These findings emphasize the importance of glycinergic postsynaptic inhibition in motor neurons and challenge the view that GABA also contributes.

Keywords
adult, GABA, glycine, inhibition, motor neuron, mouse
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-100954 (URN)10.1523/JNEUROSCI.1627-14.2015 (DOI)000349671100015 ()25653357 (PubMedID)
Available from: 2015-03-20 Created: 2015-03-16 Last updated: 2018-06-07Bibliographically approved
Azim, E. & Alstermark, B. (2015). Skilled forelimb movements and internal copy motor circuits. Current Opinion in Neurobiology, 33, 16-24
Open this publication in new window or tab >>Skilled forelimb movements and internal copy motor circuits
2015 (English)In: Current Opinion in Neurobiology, ISSN 0959-4388, E-ISSN 1873-6882, Vol. 33, p. 16-24Article in journal (Refereed) Published
Abstract [en]

Mammalian skilled forelimb movements are remarkable in their precision, a feature that emerges from the continuous adjustment of motor output. Here we discuss recent progress in bridging the gap between theory and neural implementation in understanding the basis of forelimb motor refinement. One influential theory is that feedback from internal copy motor pathways enables fast prediction, through a forward model of the limb, an idea supported by behavioral studies that have explored how forelimb movements are corrected online and can adapt to changing conditions. In parallel, neural substrates of forelimb internal copy pathways are coming into clearer focus, in part through the use of genetically tractable animal models to isolate spinal and cerebellar circuits and explore their contributions to movement.

National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-108471 (URN)10.1016/j.conb.2014.12.009 (DOI)000359960800004 ()25588912 (PubMedID)
Available from: 2015-09-22 Created: 2015-09-11 Last updated: 2018-06-07Bibliographically approved
Alstermark, B. & Ekerot, C.-F. (2015). The lateral reticular nucleus: integration of descending and ascending systems regulating voluntary forelimb movements. Frontiers in Computational Neuroscience, 9, Article ID 102.
Open this publication in new window or tab >>The lateral reticular nucleus: integration of descending and ascending systems regulating voluntary forelimb movements
2015 (English)In: Frontiers in Computational Neuroscience, ISSN 1662-5188, E-ISSN 1662-5188, Vol. 9, article id 102Article in journal (Refereed) Published
Abstract [en]

Cerebellar control of movements is dependent on mossy fiber input conveying information about sensory and premotor activity in the spinal cord. While much is known about spino-cerebellar systems, which provide the cerebellum with detailed sensory information, much less is known about systems conveying motor information. Individual motoneurones do not have projections to spino-cerebellar neurons. Instead, the fastest route is from last order spinal interneurons. In order to identify the networks that convey ascending premotor information from last order interneurons, we have focused on the lateral reticular nucleus (LRN), which provides the major mossy fiber input to cerebellum from spinal interneuronal systems. Three spinal ascending systems to the LRN have been investigated: the C3-C4 propriospinal neurones (PNs), the ipsilateral forelimb tract (iFT) and the bilateral ventral flexor reflex tract (bVFRT). Voluntary forelimb movements involve reaching and grasping together with necessary postural adjustments and each of these three interneuronal systems likely contribute to specific aspects of forelimb motor control. It has been demonstrated that the command for reaching can be mediated via C3-C4 PNs, while the command for grasping is conveyed via segmental interneurons in the forelimb segments. Our results reveal convergence of ascending projections from all three interneuronal systems in the LRN, producing distinct combinations of excitation and inhibition. We have also identified a separate descending control of LRN neurons exerted via a subgroup of cortico-reticular neurones. The LRN projections to the deep cerebellar nuclei exert a direct excitatory effect on descending motor pathways via the reticulospinal, vestibulospinal, and other supraspinal tracts, and might play a key role in cerebellar motor control. Our results support the hypothesis that the LRN provides the cerebellum with highly integrated information, enabling cerebellar control of complex forelimb movements.

Keywords
interneurons, propriospinal neurons, motoneurons, lateral reticular nucleus, cerebellum, motor ntrol, efferent copy, internal feedback
National Category
Neurology
Identifiers
urn:nbn:se:umu:diva-108465 (URN)10.3389/fncom.2015.00102 (DOI)000360180900001 ()26300768 (PubMedID)
Available from: 2015-09-22 Created: 2015-09-11 Last updated: 2018-06-07Bibliographically approved
Alstermark, B. & Pettersson, L.-G. (2014). Endogenous plasticity in neuro-rehabilitation following partial spinal cord lesions. Frontiers in Neuroscience, 8, 59
Open this publication in new window or tab >>Endogenous plasticity in neuro-rehabilitation following partial spinal cord lesions
2014 (English)In: Frontiers in Neuroscience, ISSN 1662-4548, E-ISSN 1662-453X, Vol. 8, p. 59-Article in journal (Refereed) Published
Abstract [en]

Currently, much interest in neuro-rehabilitation is focused on mechanisms related to axonal outgrowth and formation of new circuits although still little is known about the functionality in motor behavior. This is a highly exciting avenue of research and most important to consider when dealing with large lesions. Here, we address endogenous mechanisms with the potential of modifying the function of already existing spinal circuits via associative plasticity. We forward a hypothesis based on experimental findings suggesting that potentiation of synaptic transmission in un-injured pathways can be monitored and adjusted by a Cerebellar loop involving the Reticulospinal, Rubrospinal and Corticospinal tracts and spinal interneurons with projection to motoneurons. This mechanism could be of relevance when lesions are less extensive and the integrity of the neural circuits remains in part. Endogenous plasticity in the spinal cord could be of clinical importance if stimulated in an adequate manner, e.g., by using optimal training protocols.

Keywords
rehabilitation; partial spinal cord lesion; grasping; corticospinal; rubrospinal; reticulospinal; interneuron; lateral reticular nucleus
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-88636 (URN)10.3389/fnins.2014.00059 (DOI)000346445800001 ()24778603 (PubMedID)
Available from: 2014-05-12 Created: 2014-05-12 Last updated: 2018-06-07Bibliographically approved
Alstermark, B. & Pettersson, L.-G. (2014). Skilled reaching and grasping in the rat: lacking effect of corticospinal lesion. Frontiers in Neurology, 5, Article ID 103.
Open this publication in new window or tab >>Skilled reaching and grasping in the rat: lacking effect of corticospinal lesion
2014 (English)In: Frontiers in Neurology, ISSN 1664-2295, E-ISSN 1664-2295, Vol. 5, article id 103Article in journal (Refereed) Published
Abstract [en]

The corticospinal system is a major motor pathway in the control of skilled voluntary movements such as reaching and grasping. It has developed considerably phylogenetically to reach a peak in humans. Because rodents possess advanced forelimb movements that can be used for reaching and grasping food, it is commonly considered that the corticospinal tract (CST) is of major importance for this control also in rodents. A close homology to primate reaching and grasping has been described but with obvious limitations as to independent digit movements, which are lacking in rodents. Nevertheless, it was believed that there are, as in the primate, direct cortico-motoneuronal connections. Later, it was shown that there are no such connections. The fastest excitatory pathway is disynaptic, mediated via cortico-reticulospinal neurons and in the spinal cord the excitation is mainly polysynaptically mediated via segmental interneurons. Earlier behavioral studies have aimed at investigating the role of the CST by using pyramidotomy in the brainstem. However, in addition to interrupting the CST, a pyramidal transection abolishes the input to reticulospinal neurons. It is therefore not possible to conclude if the deficits after pyramidotomy result from interruption of the CST or the input to reticulospinal neurons or both. We have re-investigated the role of the CST by examining the effect of a CST lesion in the C1-C2 spinal segments on the success rate of reaching and grasping. This lesion spares the cortico-reticulospinal pathway. In contrast to investigations using pyramidal transections, the present study did not demonstrate marked deficits in reaching and grasping. We propose that the difference in results can be explained by the intact cortical input to reticulospinal neurons in our study and thus implicate an important role of this pathway in the control of reaching and grasping in the rat.

Place, publisher, year, edition, pages
Frontiers Media S.A., 2014
Keywords
corticospinal tract lesion, grasping, interneuron, motorneuron, reaching, reticulospinal, skilled forelimb movements
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-91625 (URN)10.3389/fneur.2014.00103 (DOI)000209629300100 ()24999340 (PubMedID)
Available from: 2014-08-13 Created: 2014-08-13 Last updated: 2018-06-07Bibliographically approved
Azim, E., Jiang, J., Alstermark, B. & Jessell, T. M. (2014). Skilled reaching relies on a V2a propriospinal internal copy circuit. Nature, 508(7496), 357-363
Open this publication in new window or tab >>Skilled reaching relies on a V2a propriospinal internal copy circuit
2014 (English)In: Nature, ISSN 0028-0836, E-ISSN 1476-4687, Vol. 508, no 7496, p. 357-363Article in journal (Refereed) Published
Abstract [en]

The precision of skilled forelimb movement has long been presumed to rely on rapid feedback corrections triggered by internally directed copies of outgoing motor commands, but the functional relevance of inferred internal copy circuits has remained unclear. One class of spinal interneurons implicated in the control of mammalian forelimb movement, cervical propriospinal neurons (PNs), has the potential to convey an internal copy of premotor signals through dual innervation of forelimb-innervating motor neurons and precerebellar neurons of the lateral reticular nucleus. Here we examine whether the PN internal copy pathway functions in the control of goal-directed reaching. In mice, PNs include a genetically accessible subpopulation of cervical V2a interneurons, and their targeted ablation perturbs reaching while leaving intact other elements of forelimb movement. Moreover, optogenetic activation of the PN internal copy branch recruits a rapid cerebellar feedback loop that modulates forelimb motor neuron activity and severely disrupts reaching kinematics. Our findings implicate V2a PNs as the focus of an internal copy pathway assigned to the rapid updating of motor output during reaching behaviour.

Place, publisher, year, edition, pages
Nature Publishing Group, 2014
Keywords
cerebellum, motor neuron, molecular neuroscience, spinal cord
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-86667 (URN)10.1038/nature13021 (DOI)000334403000044 ()24487617 (PubMedID)
Available from: 2014-03-04 Created: 2014-03-04 Last updated: 2018-06-08Bibliographically approved
Hao, M., He, X., Xiao, Q., Alstermark, B. & Lan, N. (2013). Corticomuscular transmission of tremor signals by propriospinal neurons in Parkinson's disease.. PLoS ONE, 8(11), Article ID e79829.
Open this publication in new window or tab >>Corticomuscular transmission of tremor signals by propriospinal neurons in Parkinson's disease.
Show others...
2013 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 8, no 11, article id e79829Article in journal (Refereed) Published
Abstract [en]

Cortical oscillatory signals of single and double tremor frequencies act together to cause tremor in the peripheral limbs of patients with Parkinson's disease (PD). But the corticospinal pathway that transmits the tremor signals has not been clarified, and how alternating bursts of antagonistic muscle activations are generated from the cortical oscillatory signals is not well understood. This paper investigates the plausible role of propriospinal neurons (PN) in C3-C4 in transmitting the cortical oscillatory signals to peripheral muscles. Kinematics data and surface electromyogram (EMG) of tremor in forearm were collected from PD patients. A PN network model was constructed based on known neurophysiological connections of PN. The cortical efferent signal of double tremor frequencies were integrated at the PN network, whose outputs drove the muscles of a virtual arm (VA) model to simulate tremor behaviors. The cortical efferent signal of single tremor frequency actuated muscle spindles. By comparing tremor data of PD patients and the results of model simulation, we examined two hypotheses regarding the corticospinal transmission of oscillatory signals in Parkinsonian tremor. Hypothesis I stated that the oscillatory cortical signals were transmitted via the mono-synaptic corticospinal pathways bypassing the PN network. The alternative hypothesis II stated that they were transmitted by way of PN multi-synaptic corticospinal pathway. Simulations indicated that without the PN network, the alternating burst patterns of antagonistic muscle EMGs could not be reliably generated, rejecting the first hypothesis. However, with the PN network, the alternating burst patterns of antagonist EMGs were naturally reproduced under all conditions of cortical oscillations. The results suggest that cortical commands of single and double tremor frequencies are further processed at PN to compute the alternating burst patterns in flexor and extensor muscles, and the neuromuscular dynamics demonstrated a frequency dependent damping on tremor, which may prevent tremor above 8 Hz to occur.

Place, publisher, year, edition, pages
Public Library of Science, 2013
National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-83835 (URN)10.1371/journal.pone.0079829 (DOI)000327313100054 ()24278189 (PubMedID)
Available from: 2013-12-10 Created: 2013-12-10 Last updated: 2018-06-08Bibliographically approved
Alstermark, B. & Ekerot, C.-F. (2013). The lateral reticular nucleus: a precerebellar centre providing the cerebellum with overview and integration of motor functions at systems level. A new hypothesis.. Journal of Physiology, 591(22), 5453-5458
Open this publication in new window or tab >>The lateral reticular nucleus: a precerebellar centre providing the cerebellum with overview and integration of motor functions at systems level. A new hypothesis.
2013 (English)In: Journal of Physiology, ISSN 0022-3751, E-ISSN 1469-7793, Vol. 591, no 22, p. 5453-5458Article in journal (Refereed) Published
Abstract [en]

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

Place, publisher, year, edition, pages
Wiley-Blackwell, 2013
National Category
Physiology
Identifiers
urn:nbn:se:umu:diva-83713 (URN)10.1113/jphysiol.2013.256669 (DOI)000326899800007 ()24042498 (PubMedID)
Funder
Swedish Research Council
Available from: 2013-12-05 Created: 2013-12-05 Last updated: 2018-06-08Bibliographically approved
Organisations

Search in DiVA

Show all publications