Reticulospinal System Research Articles

Neural coordination of bilateral hand movements: evidence for an involvement of brainstem motor centres.

Bilateral hand movements are assumed to be coordinated by a neural coupling mechanism. Neural coupling is experimentally reflected in complex electromyographic (EMG) responses in the forearm muscles of both sides to unilateral electrical arm nerve stimulation (ES). The aim of this study was to examine a potential involvement of the reticulospinal system in neural coupling by the application of loud acoustic stimuli (LAS) known to activate neurons of this system. LAS, ES and combined LAS/ES were applied to healthy subjects during visually guided bilateral hand flexion-extension movements. Muscle responses to the different stimuli were evaluated by electrophysiological recordings. Unilateral electrical ulnar nerve stimulation resulted in neural coupling responses in the forearm extensors (FE) of both sides. Interestingly, LAS evoked bilateral EMG responses that were similar in their configuration to those induced by ES. The presence of startles was associated with a shift of the onset and enhanced amplitude of LAS-induced coupling-like responses. Upon combined LAS/ES application, ES facilitated ipsilateral startles and coupling-like responses. Modulation of coupling-like responses by startles, the similarity of the responses to ES and LAS, and their interaction following combined stimulation suggests that both responses are mediated by the reticulospinal system. Our findings provide novel indirect evidence that the reticulospinal system is involved in the neural coupling of hand movements. This becomes clinically relevant in subjects with a damaged corticospinal system where a dominant reticulospinal system leads to involuntary limb coupling, referred to as associated movements. KEY POINTS: Automatic coordination of hand movements is assumed to be mediated by a neural coupling mechanism reflected by bilateral reflex responses in forearm muscles to unilateral electrical arm nerve stimulation (ES). Loud acoustic stimuli (LAS) were applied to assess a potential involvement of the reticulospinal system in the neural coupling mechanism. LAS evoked a bilateral reflex response in the forearm extensors that was similar to the neural coupling response to ES, and which could be separated from the acoustic startle response. Combined application of LAS and ES resulted in a facilitation of startle and coupling-like responses ipsilateral to ES, thus indicating an interaction of afferences from both stimuli. These novel findings provide indirect evidence that the reticulospinal system is a key motor structure for the coupling of bilateral hand movements.

Excitatory and Inhibitory Descending Commissural Interneurons Differentially Integrate Supraspinal and Segmental Sensory Signals.

The limited information about how descending inputs from the brain and sensory inputs from the periphery use spinal cord interneurons (INs) is a major barrier to understanding how these inputs may contribute to motor functions under normal and pathologic conditions. Commissural interneurons (CINs) are a heterogeneous population of spinal INs that has been implicated in crossed motor responses and bilateral motor coordination (ability to use the right and left side of the body in a coordinated manner) and, therefore, are likely involved in many types of movement (e.g., dynamic posture stabilization, jumping, kicking, walking). In this study, we incorporate mouse genetics, anatomy, electrophysiology, and single-cell calcium imaging to investigate how a subset of CINs, those with descending axons called dCINs, are recruited by descending reticulospinal and segmental sensory signals independently and in combination. We focus on two groups of dCINs set apart by their principal neurotransmitter (glutamate and GABA) and identified as VGluT2+ dCINs and GAD2+ dCINs. We show that VGluT2+ and GAD2+ dCINs are both extensively recruited by reticulospinal and sensory input alone but that VGluT2+ and GAD2+ dCINs integrate these inputs differently. Critically, we find that when recruitment depends on the combined action of reticulospinal and sensory inputs (subthreshold inputs), VGluT2+ dCINs, but not GAD2+ dCINs, are recruited. This difference in the integrative capacity of VGluT2+ and GAD2+ dCINs represents a circuit mechanism that the reticulospinal and segmental sensory systems may avail themselves of to regulate motor behaviors both normally and after injury.SIGNIFICANCE STATEMENT The way supraspinal and peripheral sensory inputs use spinal cord interneurons is fundamental to defining how motor functions are supported both in health and disease. This study, which focuses on dCINs, a heterogeneous population of spinal interneurons critical for crossed motor responses and bilateral motor coordination, shows that both glutamatergic (excitatory) and GABAergic (inhibitory) dCINs can be recruited by supraspinal (reticulospinal) or peripheral sensory inputs. Additionally, the study demonstrates that in conditions where the recruitment of dCINs depends on the combined action of reticulospinal and sensory inputs, only excitatory dCINs are recruited. The study uncovers a circuit mechanism that the reticulospinal and segmental sensory systems may avail themselves of to regulate motor behaviors both normally and after injury.

Delays in the Reticulospinal System Are Associated With a Reduced Capacity to Learn a Simulated Feeding Task in Older Adults.

Learning declines with age. Recent evidence indicates that the brainstem may play an important role in learning and motor skill acquisition. Our objective was to determine if delays in the reticular formation, measured via the startle reflex, correspond to age-related deficits in learning and retention. We hypothesized that delays in the startle reflex would be linearly correlated to learning and retention deficits in older adults. To determine if associations were unique to the reticulospinal system, we also evaluated corticospinal contributions with transcranial magnetic stimulation. Our results showed a linear relationship between startle onset latency and percent learning and retention but no relationship between active or passive motor-evoked potential onsets or peak-to-peak amplitude. These results lay the foundation for further study to evaluate if (1) the reticular formation is a subcortical facilitator of skill acquisition and (2) processing delays in the reticular formation contribute to age-related learning deficits.

PTPσ Knockdown in Lampreys Impairs Reticulospinal Axon Regeneration and Neuronal Survival After Spinal Cord Injury.

Traumatic spinal cord injury (SCI) results in persistent functional deficits due to the lack of axon regeneration within the mammalian CNS. After SCI, chondroitin sulfate proteoglycans (CSPGs) inhibit axon regrowth via putative interactions with the LAR-family protein tyrosine phosphatases, PTPσ and LAR, localized on the injured axon tips. Unlike mammals, the sea lamprey, Petromyzon marinus, robustly recovers locomotion after complete spinal cord transection (TX). Behavioral recovery is accompanied by heterogeneous yet predictable anatomical regeneration of the lamprey’s reticulospinal (RS) system. The identified RS neurons can be categorized as “good” or “bad” regenerators based on the likelihood that their axons will regenerate. Those neurons that fail to regenerate their axons undergo a delayed form of caspase-mediated cell death. Previously, this lab reported that lamprey PTPσ mRNA is selectively expressed in “bad regenerator” RS neurons, preceding SCI-induced caspase activation. Consequently, we hypothesized that PTPσ deletion would reduce retrograde cell death and promote axon regeneration. Using antisense morpholino oligomers (MOs), we knocked down PTPσ expression after TX and assessed the effects on axon regeneration, caspase activation, intracellular signaling, and behavioral recovery. Unexpectedly, PTPσ knockdown significantly impaired RS axon regeneration at 10 weeks post-TX, primarily due to reduced long-term neuron survival. Interestingly, cell loss was not preceded by an increase in caspase or p53 activation. Behavioral recovery was largely unaffected, although PTPσ knockdowns showed mild deficits in the recovery of swimming distance and latency to immobility during open field swim assays. Although the mechanism underlying the cell death following TX and PTPσ knockdown remains unknown, this study suggests that PTPσ is not a net negative regulator of long tract axon regeneration in lampreys.

Experts, but not novices, exhibit StartReact indicating experts use the reticulospinal system more than novices

Motor skill acquisition utilizes a wide array of neural structures; however, few articles evaluate how the relative contributions of these structures shift over the course of learning. Recent evidence from rodents and songbirds suggests there is a transfer from cortical to subcortical structures following intense, repetitive training. Evidence from humans indicate that the reticulospinal system is modulated over the course of skill acquisition and may be a subcortical facilitator of learning. The objective of this study was to evaluate how reticulospinal contributions are modulated by task expertise. Reticulospinal contributions were assessed using StartReact (SR). We hypothesized that expert typists would show SR during an individuated, keystroke task but SR would be absent in novices. Expert (75.2 ± 9.8 WPM) and novice typists (41.6 ± 8.2 WPM) were evaluated during an individuated, keystroke movements. In experts, SR was present but was absent in novices. Together, these results suggest that experts use reticulospinal contributions more for movement than novices indicating that the reticular formation becomes increasingly important for movement execution in highly trained, skilled tasks even those that require individuated movement of the fingers.

A startling acoustic stimulation (SAS)-TMS approach to assess the reticulospinal system in healthy and stroke subjects

Reticulospinal (RS) hyperexcitability is observed in stroke survivors with spastic hemiparesis. Habituated startle acoustic stimuli (SAS) can be used to stimulate the RS pathways non-reflexively. However, the role of RS pathways in motor function and its interactions with the corticospinal system after stroke still remain unclear. Therefore, the purpose of this study was to investigate the effects of conditioning SAS on the corticospinal system in healthy subjects and in stroke subjects with spastic hemiparesis. An established conditioning SAS- transcranial magnetic stimulation (TMS) paradigm was used to test the interactions between the RS pathways and the corticospinal system. TMS was delivered to the right hemisphere of eleven healthy subjects and the contralesional hemisphere of eleven stroke subjects during isometric elbow flexor contraction on the non-impaired (or left) side. Conditioning SAS had similar effects on the corticospinal motor system in both healthy and stroke subjects, including similar SAS-induced motor evoked potential (MEP) reduction at rest, but not during voluntary contraction tasks; similar magnitudes of TMS-induced MEP and force increment and shortening of the silent period during voluntary elbow flexor contraction. This study provides evidence that RS excitability on the contralesional side in stroke subjects with spastic hemiparesis is not abnormal, and suggests that RS projections are likely to be primarily unilateral in humans.

Reticulospinal Systems for Tuning Motor Commands.

The pontomedullary reticular formation (RF) is a key site responsible for integrating descending instructions to execute particular movements. The indiscrete nature of this region has led not only to some inconsistencies in nomenclature, but also to difficulties in understanding its role in the control of movement. In this review article, we first discuss nomenclature of the RF, and then examine the reticulospinal motor command system through evolution. These command neurons have direct monosynaptic connections with spinal interneurons and motoneurons. We next review their roles in postural adjustments, walking and sleep atonia, discussing their roles in movement activation or inhibition. We propose that knowledge of the internal organization of the RF is necessary to understand how the nervous system tunes motor commands, and that this knowledge will underlie strategies for motor functional recovery following neurological injuries or diseases.

Descending Influences on Vestibulospinal and Vestibulosympathetic Reflexes.

This review considers the integration of vestibular and other signals by the central nervous system pathways that participate in balance control and blood pressure regulation, with an emphasis on how this integration may modify posture-related responses in accordance with behavioral context. Two pathways convey vestibular signals to limb motoneurons: the lateral vestibulospinal tract and reticulospinal projections. Both pathways receive direct inputs from the cerebral cortex and cerebellum, and also integrate vestibular, spinal, and other inputs. Decerebration in animals or strokes that interrupt corticobulbar projections in humans alter the gain of vestibulospinal reflexes and the responses of vestibular nucleus neurons to particular stimuli. This evidence shows that supratentorial regions modify the activity of the vestibular system, but the functional importance of descending influences on vestibulospinal reflexes acting on the limbs is currently unknown. It is often overlooked that the vestibulospinal and reticulospinal systems mainly terminate on spinal interneurons, and not directly on motoneurons, yet little is known about the transformation of vestibular signals that occurs in the spinal cord. Unexpected changes in body position that elicit vestibulospinal reflexes can also produce vestibulosympathetic responses that serve to maintain stable blood pressure. Vestibulosympathetic reflexes are mediated, at least in part, through a specialized group of reticulospinal neurons in the rostral ventrolateral medulla that project to sympathetic preganglionic neurons in the spinal cord. However, other pathways may also contribute to these responses, including those that dually participate in motor control and regulation of sympathetic nervous system activity. Vestibulosympathetic reflexes differ in conscious and decerebrate animals, indicating that supratentorial regions alter these responses. However, as with vestibular reflexes acting on the limbs, little is known about the physiological significance of descending control of vestibulosympathetic pathways.

Implications of gamma band activity in the pedunculopontine nucleus.

The fact that the pedunculopontine nucleus (PPN) is part of the reticular activating system places it in a unique position to modulate sensory input and fight-or-flight responses. Arousing stimuli simultaneously activate ascending projections of the PPN to the intralaminar thalamus to trigger cortical high-frequency activity and arousal, as well as descending projections to reticulospinal systems to alter posture and locomotion. As such, the PPN has become a target for deep brain stimulation for the treatment of Parkinson's disease, modulating gait, posture, and higher functions. This article describes the latest discoveries on PPN physiology and the role of the PPN in a number of disorders. It has now been determined that high-frequency activity during waking and REM sleep is controlled by two different intracellular pathways and two calcium channels in PPN cells. Moreover, there are three different PPN cell types that have one or both calcium channels and may be active during waking only, REM sleep only, or both. Based on the new discoveries, novel mechanisms are proposed for insomnia as a waking disorder. In addition, neuronal calcium sensor protein-1 (NCS-1), which is over expressed in schizophrenia and bipolar disorder, may be responsible for the dysregulation in gamma band activity in at least some patients with these diseases. Recent results suggest that NCS-1 modulates PPN gamma band activity and that lithium acts to reduce the effects of over expressed NCS-1, accounting for its effectiveness in bipolar disorder.

Brainstem control of locomotion and muscle tone with special reference to the role of the mesopontine tegmentum and medullary reticulospinal systems.

The lateral part of the mesopontine tegmentum contains functionally important structures involved in the control of posture and gait. Specifically, the mesencephalic locomotor region, which may consist of the cuneiform nucleus and pedunculopontine tegmental nucleus (PPN), occupies the interest with respect to the pathophysiology of posture-gait disorders. The purpose of this article is to review the mechanisms involved in the control of postural muscle tone and locomotion by the mesopontine tegmentum and the pontomedullary reticulospinal system. To make interpretation and discussion more robust, the above issue is considered largely based on our findings in the experiments using decerebrate cat preparations in addition to the results in animal experimentations and clinical investigations in other laboratories. Our investigations revealed the presence of functional topographical organizations with respect to the regulation of postural muscle tone and locomotion in both the mesopontine tegmentum and the pontomedullary reticulospinal system. These organizations were modified by neurotransmitter systems, particularly the cholinergic PPN projection to the pontine reticular formation. Because efferents from the forebrain structures as well as the cerebellum converge to the mesencephalic and pontomedullary reticular formation, changes in these organizations may be involved in the appropriate regulation of posture-gait synergy depending on the behavioral context. On the other hand, abnormal signals from the higher motor centers may produce dysfunction of the mesencephalic-reticulospinal system. Here we highlight the significance of elucidating the mechanisms of the mesencephalic-reticulospinal control of posture and locomotion so that thorough understanding of the pathophysiological mechanisms of posture-gait disorders can be made.

Evidence for a role of the reticulospinal system in recovery of skilled reaching after cortical stroke: initial results from a model of ischemic cortical injury

The purposes of this pilot study were to create a model of focal cortical ischemia in Macaca fascicularis and to explore contributions of the reticulospinal system in recovery of reaching. Endothelin-1 was used to create a focal lesion in the shoulder/elbow representation of left primary motor cortex (M1) of two adult female macaques. Repetitive microstimulation was used to map upper limb motor outputs from right and left cortical motor areas and from the pontomedullary reticular formation (PMRF). In subject 1 with a small lesion and spontaneous recovery, reaching was mildly impaired. Changes were evident in the shoulder/elbow representations of both the lesioned and contralesional M1, and there appeared to be fewer than expected upper limb responses from the left (ipsilesional) PMRF. In subject 2 with a substantial lesion, reaching was severely impaired immediately after the lesion. After 12 weeks of intensive rehabilitative training, reach performance recovered to near-baseline levels, but movement times remained about 50% slower. Surprisingly, the shoulder/elbow representation in the lesioned M1 remained completely absent after recovery, and there was a little change in the contralesional M1. There was a definite difference in motor output patterns for left versus right PMRF for this subject, with an increase in right arm responses from right PMRF and a paucity of left arm responses from left PMRF. The results are consistent with increased reliance on PMRF motor outputs for recovery of voluntary upper limb motor control after significant cortical ischemic injury.

Reorganization of spinal neural circuitry and functional recovery after spinal cord injury

Reorganization of spinal neural circuitry and functional recovery after spinal cord injury

Cholinergic mechanisms in spinal locomotion-potential target for rehabilitation approaches.

Previous experiments implicate cholinergic brainstem and spinal systems in the control of locomotion. Our results demonstrate that the endogenous cholinergic propriospinal system, acting via M2 and M3 muscarinic receptors, is capable of consistently producing well-coordinated locomotor activity in the in vitro neonatal preparation, placing it in a position to contribute to normal locomotion and to provide a basis for recovery of locomotor capability in the absence of descending pathways. Tests of these suggestions, however, reveal that the spinal cholinergic system plays little if any role in the induction of locomotion, because MLR-evoked locomotion in decerebrate cats is not prevented by cholinergic antagonists. Furthermore, it is not required for the development of stepping movements after spinal cord injury, because cholinergic agonists do not facilitate the appearance of locomotion after spinal cord injury, unlike the dramatic locomotion-promoting effects of clonidine, a noradrenergic α-2 agonist. Furthermore, cholinergic antagonists actually improve locomotor activity after spinal cord injury, suggesting that plastic changes in the spinal cholinergic system interfere with locomotion rather than facilitating it. Changes that have been observed in the cholinergic innervation of motoneurons after spinal cord injury do not decrease motoneuron excitability, as expected. Instead, the development of a “hyper-cholinergic” state after spinal cord injury appears to enhance motoneuron output and suppress locomotion. A cholinergic suppression of afferent input from the limb after spinal cord injury is also evident from our data, and this may contribute to the ability of cholinergic antagonists to improve locomotion. Not only is a role for the spinal cholinergic system in suppressing locomotion after SCI suggested by our results, but an obligatory contribution of a brainstem cholinergic relay to reticulospinal locomotor command systems is not confirmed by our experiments.

Effect of Injury of the Cortico- and Rubro-Spinal Pathways on Operant Food-Procuring Reflexes in Cats

In experiments on cats with injury of the cortico- and rubro-spinal pathways, we studied the dynamics of recovery of operant (instrumental) food-procuring reactions at different durations of presurgery learning of animals. Operant manipulatory food-procuring movements were realized under conditions of horizontal and vertical tests, which required training for and support of a strictly defined pose in the course of performance of such movements and determined a specific pattern and stability of the coordinated motor phenomenon. The severity of abnormalities of operant food-procuring activity after transection of the lateral funiculus of the spinal cord at the level of С5-С6 and the time interval necessary for compensation of disorders of the developed manipulatory reaction depended significantly on the duration of presurgery motor learning and decreased considerably with increase in this duration. Such increase determined transformation of the pattern of postural rearrangement, which demonstrated no dependence on the amplitude and trajectory of the forthcoming operant phasic movements and was observed under conditions of both horizontal and vertical motor tests. Our results indicate that the main factor providing successful compensation of disorders of the developed operant habit in cats after injury of the cortico- and rubro-spinal pathways is active involvement of the tecto-and reticulo-spinal systems in the process of formation of the reflex. This can be due to an increase in the duration and intensity of presurgery learning of animals.

Combined corticospinal and reticulospinal effects on upper limb muscles

Both the reticulospinal and corticospinal systems are known to control recruitment of upper limb muscles, yet no known studies have attempted to assess their combined effects in the same experiment in the awake, behaving primate. The purpose of this study is to present an approach for the analysis of the cooperative control from these two motor systems. Muscle responses to electrical stimulation in the reticulospinal system and corticospinal system alone or in combination were studied. The responses were categorized based on simple neural circuits that could explain the interactions of these systems. Five such circuits were identified that could explain 86% of the observed patterns of combined recruitment during stimulation. Improved understanding of the cooperation between these motor systems could provide insight for development of better rehabilitation approaches for stroke patients and others with movement disorders.

The human extrapyramidal system

The term “extrapyramidal” originally described a collection of tegmentospinal pathways that conveyed the propagation of cortically-induced seizures to the spinal cord of dogs with bilateral transection of the pyramidal tracts. The extrapyramidal concept developed into unwarranted avenues to include forebrain structures involved in motor control, such as the basal ganglia, or as a broad synonym of clinical syndromes characterized by nonparalytic abnormal involuntary movements and postures. Clinicians and pathologists assumed that, similarly to mammals in general, the human extrapyramidal system was also organized in parallel with the pyramidal tracts. Several inconsistencies of this model, as applied to humans, were overlooked despite compelling clinicoanatomic evidence showing that (i) bilateral damage to the pyramidal tracts at any level from the pontomedullary transition to the motor cortex produces the locked-in syndrome and (ii) the extrapyramidal tracts are sparse in man. In the present essay I advance the hypothesis that the human extrapyramidal system is fundamentally different from its mammalian counterparts both anatomically and functionally. To test this hypothesis, a systematic analysis of the residual motor patterns observed on a natural model of a bilateral section of the human pyramidal tracts, the locked-in syndrome, is provided. This analysis reveals that the human extrapyramidal system underpins the organization of the following categories of motor synergies: (i) oculofacial and oculocephalic, (ii) faciorespiratory, (iii) axial-appendicular, and (iv) plurisegmental. Anatomically, these functional repertoires of motor integration are mediated by six collections of axons defined by their brainstem nuclei of origin and spinal cord destinations: reticulospinal (medial and lateral), vestibulospinal (medial and lateral), rubrospinal (lateral only), and tectospinal (medial only) fiber systems. I conclude that the extrapyramidal concept can reliably be extended to humans, albeit its physiological and anatomical scope is considerably narrower than traditionally assumed.

Erythropoietin effect on sensorimotor recovery after contusive spinal cord injury: An electrophysiological study in rats

Spinal cord injury (SCI) is a debilitating clinical condition, characterized by a complex of neurological dysfunctions. It has been shown in rats that the acute administration of recombinant human erythropoietin (rhEPO) following a contusive SCI improves the recovery of hindlimb motor function, as measured with the locomotor BBB (Basso, Beattie, Bresnahan) scale. This scale evaluates overall locomotor activity, without testing whether the rhEPO-induced motor recovery is due to a parallel recovery of sensory and/or motor pathways. Aim of the present study was to utilize an electrophysiological test to evaluate, in a rat model of contusive SCI, the transmission of both ascending and descending pathways across the damaged cord at 2, 5, 7, 11, and 30days after lesion, in animals treated with rhEPO (n=25) vs saline solution (n=25). Motor potentials evoked by epicortical stimulation were recorded in the spinal cord, and sensory-evoked potentials evoked by spinal stimulation were recorded at the cortical level. In the same animals BBB score and immunocytochemical evaluation of the spinal segments caudal to the lesion were performed. In rhEPO-treated animals results show a better general improvement both in sensory and motor transmission through spared spinal pathways, supposedly via the reticulo-spinal system, with respect to saline controls. This improvement is most prominent at relatively early times. Overall these features show a parallel time course to the changes observed in BBB score, suggesting that EPO-mediated spared spinal cord pathways might contribute to the improvement in transmission which, in turn, might be responsible for the recovery of locomotor function.

Changes in descending motor pathway connectivity after corticospinal tract lesion in macaque monkey

Damage to the corticospinal tract is a leading cause of motor disability, for example in stroke or spinal cord injury. Some function usually recovers, but whether plasticity of undamaged ipsilaterally descending corticospinal axons and/or brainstem pathways such as the reticulospinal tract contributes to recovery is unknown. Here, we examined the connectivity in these pathways to motor neurons after recovery from corticospinal lesions. Extensive unilateral lesions of the medullary corticospinal fibres in the pyramidal tract were made in three adult macaque monkeys. After an initial contralateral flaccid paralysis, motor function rapidly recovered, after which all animals were capable of climbing and supporting their weight by gripping the cage bars with the contralesional hand. In one animal where experimental testing was carried out, there was (as expected) no recovery of fine independent finger movements. Around 6 months post-lesion, intracellular recordings were made from 167 motor neurons innervating hand and forearm muscles. Synaptic responses evoked by stimulating the unlesioned ipsilateral pyramidal tract and the medial longitudinal fasciculus were recorded and compared with control responses in 207 motor neurons from six unlesioned animals. Input from the ipsilateral pyramidal tract was rare and weak in both lesioned and control animals, suggesting a limited role for this pathway in functional recovery. In contrast, mono- and disynaptic excitatory post-synaptic potentials elicited from the medial longitudinal fasciculus significantly increased in average size after recovery, but only in motor neurons innervating forearm flexor and intrinsic hand muscles, not in forearm extensor motor neurons. We conclude that reticulospinal systems sub-serve some of the functional recovery after corticospinal lesions. The imbalanced strengthening of connections to flexor, but not extensor, motor neurons mirrors the extensor weakness and flexor spasm which in neurological experience is a common limitation to recovery in stroke survivors.

Modulatory effects of the GABAergic basal ganglia neurons on the PPN and the muscle tone inhibitory system in cats.

Pedunculopontine tegmental nucleus (PPN) contributes to the control muscle tone by modulating the activities of pontomedullary reticulospinal systems during wakefulness and rapid eye movement (REM) sleep. The PPN receives GABAergic projection from the substantia nigra pars reticulata (SNr), an output nucleus of the basal ganglia. Here we examined how GABAergic SNr-PPN projection controls the activity of the pontomedullary reticulospinal tract that constitutes muscle tone inhibitory system. Intracellular recording was made from 121 motoneurons in the lumbosacral segments in decerebrate cats (n=14). Short train pulses of stimuli (3 pulses with 5 ms intervals, 10-40 mA) applied to the PPN, where cholinergic neurons were densely distributed, evoked eye movements toward to the contralateral direction and bilaterally suppressed extensor muscle activities. The identical PPN stimulation induced IPSPs, which had a peak latency of 40-50 ms with a duration of 40-50 ms, in extensor and flexor motoneurons. The late-latency IPSPs were mediated by chloride ions. Microinjection of atropine sulfate (20 mM, 0.25 ml) into the pontine reticular formation (PRF) reduced the amplitude of the IPSPs. Although conditioning stimuli applied to the SNr (40-60 mA and 100 Hz) alone did not induce any postsynaptic effects on motoneurons, it reduced the amplitude of the PPN-induced IPSPs. Subsequent injection of bicuculline (5 mM, 0.25 ml) into the PPN blocked the SNr effects. Microinjections of NMDA (5 mM, 0.25 ml) and muscimol (5 mM, 0.25 ml) into the SNr reduced and increased the amplitude of the PPN-induced IPSPs, respectively. These results suggest that GABAergic basal ganglia output controls postural muscle tone by modulating the activity of cholinergic PPN neurons which activate the muscle tone inhibitory system. The SNr-PPN projection may contribute to not only control of muscle tone during movements in wakefulness but also modulation of muscular atonia of REM sleep. Dysfunction of the SNr-PPN projection may therefore be involved in sleep disturbances in basal ganglia disorders.

The primate reticulospinal tract, hand function and functional recovery

The primate reticulospinal tract is usually considered to control proximal and axial muscles, and to be involved mainly in gross movements such as locomotion, reaching and posture. This contrasts with the corticospinal tract, which is thought to be involved in fine control, particularly of independent finger movements. Recent data provide evidence that the reticulospinal tract can exert some influence over hand movements. Although clearly secondary to the corticospinal tract in healthy function, this could assume considerable importance after corticospinal lesion (such as following stroke), when reticulospinal systems could provide a substrate for some recovery of function. We need to understand more about the abilities of the reticular formation to process sensory input and guide motor output, so that rehabilitation strategies can be optimised to work with the innate capabilities of reticular motor control.