EphA4 Is Required for Neural Circuits Controlling Skilled Reaching.

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.

The lateral reticular nucleus; integration of descending and ascending systems regulating voluntary forelimb movements.

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.

Direct and indirect spino-cerebellar pathways: shared ideas but different functions in motor control.

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.

Not GABA but glycine mediates segmental, propriospinal, and bulbospinal postsynaptic inhibition in adult mouse spinal forelimb motor neurons.

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.

Skilled forelimb movements and internal copy motor circuits.

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.

Skilled reaching and grasping in the rat: lacking effect of corticospinal lesion.

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.

Endogenous plasticity in neuro-rehabilitation following partial spinal cord lesions.

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.

Skilled reaching relies on a V2a propriospinal internal copy circuit.

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.

Corticomuscular transmission of tremor signals by propriospinal neurons in Parkinson's disease.

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.

The lateral reticular nucleus: a precerebellar centre providing the cerebellum with overview and integration of motor functions at systems level. A new hypothesis.

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.

Genetic dissection of the circuit for hand dexterity in primates.

It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates. 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), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta).

Circuits for skilled reaching and grasping.

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.

Motor command for precision grip in the macaque monkey can be mediated by spinal interneurons.

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.

Building a realistic neuronal model that simulates multi-joint arm and hand movements in 3D space.

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.

Direct and indirect cortico-motoneuronal pathways and control of hand/arm movements.

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.

Skilled digit movements in feline and primate--recovery after selective spinal cord lesions.

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.

The C3-C4 propriospinal system in the cat and monkey: a spinal pre-motoneuronal centre for voluntary motor control.

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.

Improved organotypic cell culture model for analysis of the neuronal circuit involved in the monosynaptic stretch reflex.

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.

Properties of propriospinal neurons in the C3-C4 segments mediating disynaptic pyramidal excitation to forelimb motoneurons in the macaque monkey.

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.

Dexterous finger movements in primate without monosynaptic corticomotoneuronal excitation.

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.

In vivo recordings of bulbospinal excitation in adult mouse forelimb motoneurons.

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.

Lack of monosynaptic corticomotoneuronal EPSPs in rats: disynaptic EPSPs mediated via reticulospinal neurons and polysynaptic EPSPs via segmental interneurons.

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).

Premotoneuronal and direct corticomotoneuronal control in the cat and macaque monkey.

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.

Interruption of a relay of corticospinal excitation by a spinal lesion at C6-C7.

In a patient with a limited lesion of the spinal cord at the C6-C7 junction, ulnar and superficial radial-induced modulations of the motor evoked potentials (MEP) and of ongoing electromyographic (EMG) activity were observed in the biceps (above the lesion) but not in the triceps (below the lesion). This suggests an interruption of the axons of cervical propriospinal neurons. This relay transmits an indirect (disynaptic) component of corticospinal excitation to human upper limb motoneurons.