| 1. |
- Alstermark, Bror, et al.
(författare)
-
Anders Lundberg (1920-2009)
- 2010
-
Ingår i: Experimental Brain Research. - : Springer. - 0014-4819 .- 1432-1106. ; 200:3-4, s. 193-195
-
Tidskriftsartikel (populärvet., debatt m.m.)abstract
- Anders Lundberg was one of the founding editorial board members for EBR when it began its life in 1976 under the editorship of John Eccles. He was also one of the most prolific contributors to the journal with a total of 49 papers, including a series of 16 on the topic of "integration in descending motor pathways controlling the forelimb in the cat". He continued as an editor of the journal until volume 16 when he persuaded his younger colleague Hans Hultborn to take his place. Hans is one of the authors of the obituary. –John Rothwell
|
|
| 2. |
|
|
| 3. |
- Alstermark, Bror, et al.
(författare)
-
Building a realistic neuronal model that simulates multi-joint arm and hand movements in 3D space
- 2007
-
Ingår i: HFSP Journal. - : Informa UK Limited. - 1955-2068. ; 1:4, s. 209-214
-
Tidskriftsartikel (refereegranskat)abstract
- The question as to how the brain controls voluntary movements of the arm and hand still remains largely unsolved despite much research focused on behavioral studies, neurophysiological investigations, and neuronal modeling in computer science. This is because behavioral studies are usually performed without detailed knowledge of the underlying neuronal networks, neurophysiological studies often lack an understanding of the function, and neuronal models are frequently focused on a particular control problem with restricted knowledge of the underlying neuronal networks involved. Therefore, it seems appropriate to start by trying to integrate knowledge of neuronal networks with known function and computer based neuronal models to seek more realistic models that can better control robots or artificial limbs and hands. We propose to combine knowledge of a behavioral model for reaching with the hand toward an object, which is based on detailed knowledge of the underlying neuronal network, and a neuronal model that includes several functional levels, from the planning level via intermediate levels to the final level of control of motoneurons and muscles.
|
|
| 4. |
- Alstermark, Bror, et al.
(författare)
-
Circuits for skilled reaching and grasping
- 2012
-
Ingår i: Annual Review of Neuroscience. - Palo alto : ANNUAL REVIEWS. - 1545-4126. - 9780824324353 ; , s. 559-578
-
Bokkapitel (refereegranskat)abstract
- From an evolutionary perspective, it is clear that basic motor functions such as locomotion and posture are largely controlled by neural circuitries residing in the spinal cord and brain-stem. The control of voluntary movements such as skillful reaching and grasping is generally considered to be governed by neural circuitries in the motor cortex that connect directly to motoneurons via the corticomotoneuronal (CM) pathway. The CM pathway may act together with several brain-stem systems that also act directly with motoneurons. This simple view was challenged by work in the cat, which lacks the direct CM system, showing that the motor commands for reaching and grasping could be mediated via spinal interneurons with input from the motor-cortex and brain-stem systems. It was further demonstrated that the spinal interneurons mediating the descending commands for reaching and grasping constitute separate and distinct populations from those involved in locomotion and posture. The aim of this review is to describe populations of spinal interneurons that are involved in the control of skilled reaching and grasping in the cat, monkey, and human.
|
|
| 5. |
- Alstermark, Bror, et al.
(författare)
-
Endogenous plasticity in neuro-rehabirtation following partial spinal cord lesions
- 2014
-
Ingår i: Frontiers in Neuroscience. - : Frontiers Media SA. - 1662-453X .- 1662-4548. ; 8
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 6. |
- Alstermark, Bror, et al.
(författare)
-
In vivo recordings of bulbospinal excitation in adult mouse forelimb motoneurons.
- 2004
-
Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 92:3, s. 1958-62
-
Tidskriftsartikel (refereegranskat)abstract
- Here we report on pyramidal and reticulospinal excitation in forelimb motoneurons in the adult mouse using intracellular recordings in vivo. The results have been obtained in BALB/C mice, which were anesthetized with midazolam fentanyl/fluanison. In contrast to the rat, only weak and infrequent pyramidal excitation could be evoked with a minimal trisynaptic linkage. Disynaptic reticulospinal excitation could always be evoked, as well as monosynaptic excitation from the medial longitudinal fasciculus. The results suggest that the reticulospinal pathway in the mouse is important in voluntary motor control of the forelimbs and that the role of the corticospinal tract might be different in mouse compared with rat. Our study provides an opening for studying the effect of genetic manipulation on specified descending systems in the mouse in vivo.
|
|
| 7. |
- Alstermark, Bror, et al.
(författare)
-
Lack of monosynaptic corticomotoneuronal EPSPs in rats : disynaptic EPSPs mediated via reticulospinal neurons and polysynaptic EPSPs via segmental interneurons.
- 2004
-
Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 91:4, s. 1832-9
-
Tidskriftsartikel (refereegranskat)abstract
- In the rat, some findings have been taken to suggest the existence of monosynaptic corticomotoneuronal (CM) connections. Because this connection is believed to be largely responsible for the ability to make independent digit movements in primates and man, it has been inferred that the monosynaptic CM connection in the rat is likewise important for skilled prehension. Comparison of intra- and extracellular recordings from forelimb motoneurons in anesthetized rats, revealed no monosynaptic CM excitatory postsynaptic potentials (EPSPs). The fastest descending excitation in forelimb motoneurons was disynaptically mediated via a corticoreticulospinal pathway and slowly conducted excitation via corticospinal fibers and segmental interneurons. The findings stress the importance of di- and trisynaptic excitatory corticofugal pathways to forelimb motoneurons in the control of skillful digit movements.
|
|
| 8. |
- Alstermark, Bror, et al.
(författare)
-
Motor command for precision grip in the macaque monkey can be mediated by spinal interneurons
- 2011
-
Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 106:1, s. 122-126
-
Tidskriftsartikel (refereegranskat)abstract
- In motor control, the general view is still that spinal interneurons mainly contribute to reflexes and automatic movements. The question raised here is whether spinal interneurons can mediate the cortical command for independent finger movements, like a precision grip between the thumb and index finger in the macaque monkey, or if this function depends exclusively on a direct corticomotoneuronal pathway. This study is a followup of a previous report (Sasaki et al. J Neurophysiol 92: 3142-3147, 2004) in which we trained macaque monkeys to pick a small piece of sweet potato from a cylinder by a precision grip between the index finger and thumb. We have now isolated one spinal interneuronal system, the C3-C4 propriospinal interneurons with projection to hand and arm motoneurons. In the previous study, the lateral corticospinal tract (CST) was interrupted in C4/C5 (input intact to the C3-C4 propriospinal interneurons), and in this study, the CST was interrupted in C2 (input abolished). The precision grip could be performed within the first 15 days after a CST lesion in C4/C5 but not in C2. We conclude that C3-C4 propriospinal interneurons also can carry the command for precision grip.
|
|
| 9. |
- Alstermark, Bror, et al.
(författare)
-
Premotoneuronal and direct corticomotoneuronal control in the cat and macaque monkey.
- 2002
-
Ingår i: Advances in Experimental Medicine and Biology. - 0065-2598 .- 2214-8019. ; 508, s. 281-97
-
Tidskriftsartikel (refereegranskat)abstract
- The literature on premotoneuronal and direct corticomotoneuronal (CM) control in the cat and macaque monkey is reviewed. The available experimental findings are not in accordance with a recently proposed hypothesis that direct CM connections have "replaced" the premotoneuronal pathways. Instead, we propose that premotoneuronal CM control plays an important role in motor control also in primates and that the direct CM connection has been added during phylogeny.
|
|
| 10. |
- Alstermark, Bror, et al.
(författare)
-
Skilled reaching and grasping in the rat: Lacking effect of corticospinal lesion
- 2014
-
Ingår i: Frontiers in Neurology. - : Frontiers Research Foundation. - 1664-2295. ; 5
-
Tidskriftsartikel (refereegranskat)abstract
- 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. © 2014 Alstermark and Pettersson.
|
|
| 11. |
- Alstermark, Bror, et al.
(författare)
-
The C3-C4 propriospinal system in the cat and monkey: a spinal pre-motoneuronal centre for voluntary motor control.
- 2007
-
Ingår i: Acta physiologica (Oxford, England). - : Wiley. - 1748-1708 .- 1748-1716. ; 189:2, s. 123-40
-
Tidskriftsartikel (refereegranskat)abstract
- This review deals with a spinal interneuronal system, denoted the C3-C4 propriospinal system, which is unique in the sense that it so far represents the only spinal interneuronal system for which it has been possible to demonstrate a command mediating role for voluntary movements. The C3-C4 propriospinal neurones govern target reaching and can update the descending cortical command when a fast correction is required of the movement trajectory and also integrate signals generated from the forelimb to control deceleration and termination of reaching.
|
|
| 12. |
- Alstermark, Bror, et al.
(författare)
-
The lateral reticular nucleus : integration of descending and ascending systems regulating voluntary forelimb movements
- 2015
-
Ingår i: Frontiers in Computational Neuroscience. - : Frontiers Media SA. - 1662-5188. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 13. |
- Alstermark, Bror, et al.
(författare)
-
The lateral reticular nucleus : a precerebellar centre providing the cerebellum with overview and integration of motor functions at systems level. A new hypothesis.
- 2013
-
Ingår i: Journal of Physiology. - : Wiley-Blackwell. - 0022-3751 .- 1469-7793. ; 591:22, s. 5453-5458
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 14. |
- Azim, Eiman, et al.
(författare)
-
Skilled forelimb movements and internal copy motor circuits
- 2015
-
Ingår i: Current Opinion in Neurobiology. - : Elsevier BV. - 0959-4388 .- 1873-6882. ; 33, s. 16-24
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 15. |
- Azim, Eiman, et al.
(författare)
-
Skilled reaching relies on a V2a propriospinal internal copy circuit
- 2014
-
Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 508:7496, s. 357-363
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 16. |
- Dagberg, Björn, et al.
(författare)
-
Improved organotypic cell culture model for analysis of the neuronal circuit involved in the monosynaptic stretch reflex.
- 2006
-
Ingår i: Journal of Neuroscience Research. - : Wiley. - 0360-4012 .- 1097-4547. ; 84:2, s. 460-9
-
Tidskriftsartikel (refereegranskat)abstract
- Knowledge regarding neuronal circuit formation is central for the understanding of the vast network making up the brain. It is therefore necessary to find novel ways to analyze the mechanisms involved in well-defined neural circuits. We present an improved in vitro model of the monosynaptic stretch reflex circuit, based on primary organotypic cell cultures. By using limb tissue as a source of muscle fibers instead of circumspinal tissue we could make the in vitro system more in vivo like in the sense that it focuses on the stretch reflex involving limb muscles. Furthermore, our analyses showed that this procedure allows muscle fibers to follow the normal developmental pattern. Particularly interesting was the finding of slow tonic myosin heavy chain expressing muscle fibers, a developmental marker for muscle spindles, in the cultures showing that this system has the potential to contain the complete reflex circuits.
|
|
| 17. |
- Hao, Manzhao, et al.
(författare)
-
Corticomuscular transmission of tremor signals by propriospinal neurons in Parkinson's disease.
- 2013
-
Ingår i: PLOS ONE. - : Public Library of Science. - 1932-6203. ; 8:11
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 18. |
- Isa, Tadashi, et al.
(författare)
-
Direct and indirect cortico-motoneuronal pathways and control of Hand/Arm movements
- 2007
-
Ingår i: PHYSIOLOGY. - : American Physiological Society. - 1548-9213 .- 1548-9221. ; 22, s. 145-152
-
Tidskriftsartikel (refereegranskat)abstract
- Recent studies from our group have demonstrated the existence of a disynaptic excitatory cortico-motoneuronal (CM) pathway in macaque monkeys via propriospinal neurons in the midcervical segments. Results from behavioral studies with lesion of the direct pathway suggest that the indirect CM pathway can mediate the command for dexterous finger movements.
|
|
| 19. |
- Isa, Tadashi, et al.
(författare)
-
Properties of propriospinal neurons in the C3-C4 segments mediating disynaptic pyramidal excitation to forelimb motoneurons in the macaque monkey.
- 2006
-
Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 95:6, s. 3674-85
-
Tidskriftsartikel (refereegranskat)abstract
- Candidate propriospinal neurons (PNs) that mediate disynaptic pyramidal excitation to forelimb motoneurons were studied in the C3-C4 segments in anesthetized macaque monkeys (n = 10). A total of 177 neurons were recorded (145 extracellularly, 48 intracellularly, and 16 both) in laminae VI-VII. Among these, 86 neurons (73 extracellularly, 14 intracellularly and 1 both) were antidromically activated from the forelimb motor nucleus or from the ventrolateral funiculus just lateral to the motor nucleus in the C6/C7 segments and thus are identified as PNs. Among the 73 extracellularly recorded PNs, 60 cells were fired by a train of four stimuli to the contralateral pyramid with segmental latencies of 0.8-2.2 ms, with most of them (n = 52) in a monosynaptic range (<1.4 ms including one synaptic delay and time to firing). The firing probability was only 21% from the third pyramidal volley but increased to 83% after intravenous injection of strychnine. In most of the intracellularly recorded PNs, stimulation of the contralateral pyramid evoked monosynaptic excitatory postsynaptic potentials (EPSPs, 12/14) and disynaptic inhibitory postsynaptic potentials (14/14), which were found to be glycinergic. In contrast, cells that did not project to the C6-Th1 segments where forelimb motoneurons are located were classified as segmental interneurons. These were fired from the third pyramidal volley with a probability of 71% before injection of strychnine. It is proposed that some of these interneurons mediate feed-forward inhibition to the PNs. These results suggest that the C3-C4 PNs receive feed-forward inhibition from the pyramid in addition to monosynaptic excitation and that this inhibition is stronger in the macaque monkey than in the cat. Another difference with the cat was that only 26 of the 86 PNs (30%, as compared with 84% in the cat) with projection to the forelimb motor nuclei send ascending collaterals terminating in the lateral reticular nucleus (LRN) on the ipsilateral side of the medulla. Thus we identified C3-C4 PNs that could mediate disynaptic pyramidal excitation to forelimb motoneurons in the macaque monkey. The present findings explain why it was difficult in previous studies of the macaque monkey to evoke disynaptic pyramidal excitation via C3-C4 PNs in forelimb motoneurons and why-as compared with the cat-the monosynaptic EPSPs evoked from the LRN via C3-C4 PNs were smaller in amplitude.
|
|
| 20. |
- Jiang, Juan, et al.
(författare)
-
Direct and indirect spino-cerebellar pathways : shared ideas but different functions in motor control
- 2015
-
Ingår i: Frontiers in Computational Neuroscience. - : Frontiers Media. - 1662-5188. ; 9
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 21. |
|
|
| 22. |
- Jiang, Juan, et al.
(författare)
-
EphA4 Is Required for Neural Circuits Controlling Skilled Reaching
- 2020
-
Ingår i: Journal of Neuroscience. - : SOC NEUROSCIENCE. - 0270-6474 .- 1529-2401. ; 40:37, s. 7091-7104
-
Tidskriftsartikel (refereegranskat)abstract
- Skilled forelimb movements are initiated by feedforward motor commands conveyed by supraspinal motor pathways. The accuracy of reaching and grasping relies on internal feedback pathways that update ongoing motor commands. In mice lacking the axon guidance molecule EphA4, axonal misrouting of the corticospinal tract and spinal interneurons is manifested, leading to a hopping gait in hindlimbs. Moreover, mice with a conditional forebrain deletion of EphA4, display forelimb hopping in adaptive locomotion and exploratory reaching movements. However, it remains unclear how loss of EphA4 signaling disrupts function of forelimb motor circuit and skilled reaching and grasping movements. Here we investigated how neural circuits controlling skilled reaching were affected by the loss of EphA4. Both male and female C57BL/6 wild-type, heterozygous EphA41/2, and homozygous EphA42/2 mice were used in behavioral and in vivo electrophysiological investigations. We found that EphA4 knock-out (2/2) mice displayed impaired goal-directed reaching movements. In vivo intracellular recordings from forelimb motor neurons demonstrated increased corticoreticulospinal excitation, decreased direct reticulospinal excitation, and reduced direct propriospinal excitation in EphA4 knock-out mice. Cerebellar surface recordings showed a functional perturbation of the lateral reticular nucleus-cerebellum internal feedback pathway in EphA4 knock-out mice. Together, our findings provide in vivo evidence at the circuit level that loss of EphA4 disrupts the function of both feedforward and feedback motor pathways, resulting in deficits in skilled reaching.
|
|
| 23. |
- Jiang, Juan, et al.
(författare)
-
Not GABA But Glycine Mediates Segmental, Propriospinal, and Bulbospinal Postsynaptic Inhibition in Adult Mouse Spinal Forelimb Motor Neurons
- 2015
-
Ingår i: Journal of Neuroscience. - 0270-6474 .- 1529-2401. ; 35:5, s. 1991-1998
-
Tidskriftsartikel (refereegranskat)abstract
- 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.
|
|
| 24. |
- Kinoshita, Masaharu, et al.
(författare)
-
Genetic dissection of the circuit for hand dexterity in primates
- 2012
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 487:7406, s. 235-U1510
-
Tidskriftsartikel (refereegranskat)abstract
- It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates(1-3). However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs)(4-6), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex-PN-motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.
|
|
| 25. |
|
|
| 26. |
- Pettersson, L-G, et al.
(författare)
-
Skilled digit movements in feline and primate--recovery after selective spinal cord lesions.
- 2007
-
Ingår i: Acta Physiologica. - : Wiley. - 1748-1708 .- 1748-1716. ; 189:2, s. 141-54
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Recovery of voluntary movements after partial spinal cord injury depends, in part, on a take-over of function via unlesioned pathways. Using precise forelimb movements in the cat as model, spinal pathways contributing to motor restitution have been investigated in more detail. The food-taking movement by which the cat graSPS a morsel of food with the digits and brings it to the mouth is governed by interneurones in the forelimb segments (C6-Th1) and is normally controlled via the cortico- and rubrospinal tracts. Food-taking disappears after transection of these pathways in the dorsal part of the lateral funiculus (DLF) in C5/C6, but then recovers during a period of 2-3 weeks. Experiments with double lesions showed that the recovery depends on a take-over via ipsilateral ventral systems; a ventrally descending pathway, most probably cortico-reticulospinal, and a pathway via propriospinal neurones in the C3-C4 segments. It is postulated that the recovery involves a plastic reorganization of these systems. Dexterous finger movements in the macaque monkey are generally considered to depend on the monosynaptic cortico-motoneuronal (CM) connexion, which is lacking in the cat. Such movements are abolished after pyramidotomy at the level of the trapezoid body. However, experiments with transection of the corticospinal tract in the DLF and partly ventral part of the lateral funiculus in C5, showed a fast (1-28 days) recovery of precision grip and, to some extent, independent finger movements. Deficits in preshaping during the final approach to the morsel as well as lack of force were observed. A C5 DLF lesion spares corticofugal pathways to the brainstem and upper cervical segments. It is suggested that indirect corticomotoneuronal pathways may provide for recovery of dexterous finger movements and that the role of CM pathways for such movements should be broadened to include not only the monosynaptic connexion.
|
|
| 27. |
|
|
| 28. |
- Sasaki, S, et al.
(författare)
-
Dexterous finger movements in primate without monosynaptic corticomotoneuronal excitation
- 2004
-
Ingår i: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 92:5, s. 3142-3147
-
Tidskriftsartikel (refereegranskat)abstract
- It is generally accepted that the precision grip and independent finger movements (IFMs) in monkey and man are controlled by the direct (monosynaptic) corticomotoneuronal (CM) pathway. This view is based on previous observations that pyramidotomy causes near permanent deficits of IFMs. However, in addition to the direct CM pathway, pyramidotomy interrupts several corticofugal connections to the brain stem and upper cervical segments. Indirect (oligosynaptic) CM pathways, which are phylogenetically older, have been considered to be of little or no importance in prehension. In three adult macaque monkeys, complete transection of the direct CM pathway was made in C4/C5, which is rostral to the forelimb segments (C6–Th1). Electrophysiological recordings revealed lack of the direct lateral corticospinal tract (LCST) volley, monosynaptic extracellular field potentials in the motor nuclei, and monosynaptic CM excitation. However, a disynaptic volley, disynaptic field potentials and disynaptic CM excitation mediated via C3–C4 propriospinal neurons remained after the lesion. Thus the lesion interrupted the monosynaptic CM pathway and oligosynaptic LCST pathways mediated by interneurons in the forelimb segments. Precision grip and IFMs were observed already after 1–28 days postoperatively. Weakness in force and deficits in preshaping remained for an observation period of 3 mo. Indirect CM pathways may be important for neuro-rehabilitation.
|
|
