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Influence of sensory deprivation and perturbation of trigeminal afferent fibers on corticomotor control of human tongue musculature.

Several recent studies with transcranial magnetic stimulation (TMS) have demonstrated changes in motor evoked potentials (MEPs) in human limb muscles following modulation of sensory afferent inputs, but little is known about the regulation of the human tongue motor control. To test the effect of local anesthesia (LA) of the lingual nerve and topical application of capsaicin stimulation on tongue MEPs. Fourteen volunteers participated (21-30 years) in two randomized sessions; before, during a nerve block of the lingual nerve or topical capsaicin application (30 microl 5%) on the tongue, and after anesthesia or pain had subsided. EMG electrodes were placed on the tongue and the first dorsal interosseous (FDI) muscle (control). EMG signals were amplified, filtered (20 Hz-1 kHz), and sampled at 4 kHz (Nicolet, USA). TMS were delivered with a figure-of-eight coil (Magstim 200, UK). Scalp sites at which EMG responses were evoked in the relaxed tongue or FDI at the lowest stimulus strength were determined, i.e., motor threshold (T). MEPs were assessed using stimulus-response curves in steps of 10% T. Eight stimuli were presented at each stimulus level. The proximal hypoglossal nerve was activated by TMS delivered over the parieto-occipital skull distal to the right ear. Eight stimuli were delivered at 50% of maximum stimulator output. ANOVAs were used to analyze latency and peak-to-peak amplitudes. Capsaicin evoked mild pain (2.8+/-0.5), and a strong burning sensation (6.2+/-0.4) on 0-10 visual analogue scales. MEP amplitudes in tongue and FDI were not influenced by capsaicin (P>0.44) but by stimulus strength (P<0.001). MEP latencies in tongue (8.9+/-0.2 ms) and FDI (22.4+/-0.4 ms) were not affected by capsaicin (P>0.19). Hypoglossal nerve stimulation evoked a short-latency (3.6+/-0.9 ms) response (mean amplitude 65+/-9 microV); but was unaffected by capsaicin (P>0.54). LA did not have any effect on FDI MEPs but was associated with a significant facilitation of tongue MEPs at T+50% and T+60% about 50 min after the nerve block in the recovery phase. Also in this condition, the direct motor responses evoked by hypoglossal nerve stimulation remained constant. No direct effect of a strong burning sensation could be shown on peripheral or central corticomotor pathways to the relaxed tongue musculature, however, LA of the lingual nerve (cranial nerve V) seems able to induce a delayed change in corticomotor control of tongue musculature (cranial nerve XII) possibly related to unmasking effects at the cortical level but not completely excluding excitability changes at the brain stem level.

Adult↗

The three-neuron corneal reflex circuit and modulation of second-order corneal responsive neurons.

Neurons located in the border region between the interpolaris and caudalis subdivisions of the spinal trigeminal nucleus (Vi/Vc) are second order neurons of the corneal reflex, receiving corneal afferents and projecting to the lid closing, orbicularis oculi (OO) motoneurons. Recordings of Vi/Vc neurons identified by antidromic activation from stimulation of the facial nucleus and non-identified Vi/Vc neurons reveal two neuron types, phasic and tonic. Corneal stimulation elicits Adelta latency action potentials that occur early enough to initiate OO contraction and C-fiber latency action potentials that can modulate the end of the blink in phasic Vi/Vc neurons. Tonic Vi/Vc neurons exhibit a constant irregular, low frequency discharge as well as the cornea-evoked activity exhibited by phasic neurons. For both phasic and tonic neurons, blink amplitude increases with the total number of spikes evoked by the corneal stimulus. Peak firing frequency predicts peak orbicularis oculi EMG activity. Paradigms that suppress cornea-evoked blinks differentially affect Vi/Vc neurons. Microstimulation of the border region between the spinal trigeminal caudalis subdivision and the C1 spinal cord (Vc/C1) significantly reduces the number of spikes evoked by corneal stimulation and suppresses blink amplitude. In the paired stimulus paradigm, a blink evoked by a corneal stimulus 150 ms after an identical corneal stimulus is significantly smaller than the blink elicited by the first stimulus. Vi/Vc neuron discharge, however, is slightly larger for the second blink. Our data indicate that second-order Vi/Vc neurons do not determine the specific pattern of OO muscle activity; rather Vi/Vc neurons initiate OO motoneuron discharge and program the activity of another circuit that generates the late phase of the blink. The Vc/C1 suppression of Vi/Vc neurons suggests that the Vc/C1 region provides an "internal model" of the intended blink.

Action Potentials↗

A model of activity-dependent formation of cerebellar microzones.

According to modern views of the cerebellum in motor control, each cerebellar functional unit, or microzone, learns how to execute predictive and coordinative control, based on long-term depression of the granule cell-Purkinje cell synapses. In the present paper, in light of recent experimental and theoretical studies on synaptic elimination and cerebellar motor learning, a model of the formation of cerebellar microzones by climbing fiber synaptic elimination is proposed. It is shown that competition for an activity-dependent supply of neurotrophic factor can reproduce the spatio-temporal characteristics of climbing fiber synaptic elimination. It is further shown that when this elimination is accurate, motor coordination can be acquired in an arm reaching task. In view of the results of the present study, several predictions are proposed.

Adult↗

Localization and physiological roles of metabotropic glutamate receptors in the direct and indirect pathways of the basal ganglia.

Our current understanding of the circuitry of the basal ganglia, and the pathophysiology of Parkinson's disease has led to major breakthroughs in the treatment of this debilitating movement disorder. Unfortunately, there are significant problems with the currently available pharmacological therapies that focus on dopamine replacement or dopaminergic agonists. Because of this, much effort has been focused on developing novel targets for the treatment of Parkinson's disease. The metabotropic glutamate receptors are a family of G-protein coupled receptors activated by glutamate. These receptors are differentially distributed throughout the basal ganglia in a manner suggesting that they may provide novel targets for the treatment of movement disorders. In this review we summarize anatomical and physiological data from our work and the work of other laboratories describing the distribution and physiological roles of metabotropic glutamate receptors in the basal ganglia with emphasis on possible therapeutic targets.

Afferent Pathways↗

Laminar connections of the cat's auditory cortex.

The retrograde and the anterograde transport of horseradish peroxidase were used to study the connections established by cells in different layers of the cat's primary auditory cortex (AI). Injections of peroxidase into the medial geniculate body show that pyramidal cells in layers V and VI of AI are the sources of the corticothalamic projections. Large pyramidal cells in the outer rim of layer V also send their axons to the inferior colliculus, and it is possible that some of these cells have axons that branch to innervate both the inferior colliculus and the medial geniculate body. Cells in AI that give rise to callosal axons lie principally in layers III and VI. The callosal neurons are found in irregular clusters as wide as 1100 microgram separated by spaces that contain relatively few callosal neurons. Experiments utilizing the anterograde transport of peroxidase show that callosal terminals are found in bands running from layers VI through I. These bands are about 500 microgram in width, and the terminals seem most densely packed in layers II and III. Since the dimensions of the cell clusters and bands of callosal terminals are not the same, it is likely that not all zones which give rise to callosal axons also receive them. The bands of callosal terminals labeled by orthograde transport may be seen in the same section along with the cell bodies labeled by retrograde transport, and the two zones of label are clearly not coextensive. Complete reciprocity, therefore, seems to be absent in the callosal auditory pathway.

Animals↗

Projections of the pedunculopontine tegmental nucleus in the rat: evidence for additional extrapyramidal circuitry.

The projections of the pedunculopontine tegmental nucleus (PPT) were studied in the rat using anterograde and retrograde transport methods. Ascending fibers to the substantia nigra, the subthalamic nucleus, the globus pallidus, the entopeduncular nucleus, the neostriatum, the ventral thalamus, and the medial and sulcal frontal cortical areas were identified. PPT has been reported to receive afferents from the substantia nigra, the subthalamic nucleus, the entopeduncular nucleus and the neostriatum. The connections of PPT provide an additional limb to extrapyramidal circuitry.

Afferent Pathways↗

Electrophysiological analysis of the ascending and descending components of the micturition reflex pathway in the rat.

Electrophysiological techniques were used to examine the organization of the spinobulbospinal micturition reflex pathway in the rat. Electrical stimulation of afferent axons in the pelvic nerve evoked a long latency (136 +/- 41 ms) response on bladder postganglionic nerves, whereas stimulation in the dorsal pontine tegmentum elicited shorter latency firing (72 +/- 25 ms) on these nerves. Transection of the pelvic nerve eliminated these responses. Firing on the bladder postganglionic nerves was evoked by stimulation in a relatively limited area of the pons within and close to the laterodorsal tegmental nucleus (LDT) and adjacent ventral periaqueductal gray. Stimulation at sites ventral to this excitatory area inhibited at latencies of 107 +/- 11 ms the asynchronous firing on the bladder postganglionic nerves elicited by bladder distension. Electrical stimulation of afferents in the pelvic nerve evoked short latency (13 +/- 3 ms) negative field potentials in the dorsal part of the periaqueductal gray as well as long latency (42 +/- 7 ms) field potentials in and adjacent to the LDT. The responses were not altered by neuromuscular blockade. Similar responses were elicited by stimulation of afferent axons in the bladder nerves. The sum of the latencies of the ascending and descending pathways between the LDT and the pelvic nerve (i.e. 72 ms plus 42 ms = 114 ms) is comparable although somewhat shorter (22 ms) than the latency of the entire micturition reflex. These results provide further evidence that the micturition reflex in the rat is mediated by a spinobulbospinal pathway which passes through the dorsal pontine tegmentum, and that neurons in the periaqueductal gray as well as the LDT may play as important role in the regulation of the micturition.

Afferent Pathways↗

Structural and regenerative changes in deafferented and deefferented ulnar nerves.

Both brachial plexuses of Wistar rats were deafferented or deefferented by disrupting their dorsal or ventral roots. At the same time, the ulnar nerves were transected and sutured. A sham group and another group in which the upper (C-5) and lower (T-1) spinal nerves were transected on both sides were included as control groups. Clear differences in the ulnar nerve regeneration rate were found between the deafferented and the deefferented animals. Ultrastructural studies disclosed signs of transient axonopathy in the nontransected fibers of the proximal segment of the ulnar nerve. The possible role of bioelectricity in the genesis of these changes is discussed.

Afferent Pathways↗

Neurohumoral mechanism of space motion sickness.

This paper reviews existing hypotheses concerning the mechanisms of adaptation of the vestibular apparatus and related somatosensory systems to microgravity with reference to the flight data. Having in view theoretical concepts and experimental data accumulated in space flights, a conceptual model of the development of a funtional system responsible for the termination of vestibular dysfuntion and space motion sickness manifestations is presented. It is also shown that changes in the hormonal status during motion sickness induced by vestibular stimulation give evidence that endocrine regulation of certain functions can be involved in adaptive responses.

Adaptation, Physiological↗

A retino-pulvinar projection in the macaque monkey as visualized by the use of anterograde transport of horseradish peroxidase.

A direct retino-pulvinar connection was found in the Japanese monkey (Macaca fuscata) by the anterograde horseradish peroxidase (HRP) method. HRP injected into the vitreous cavity of one eye labeled a few small clusters of optic fiber terminals in the medial border regions of the inferior pulvinar nucleus bilaterally, with a contralateral predominance.

Afferent Pathways↗

Cells of origin of ascending and descending as well as branching fibers in the cervical spinal cord of the pigeon.

Ascending and descending projections of spinal neurons (cervical enlargement) were studied with the retrograde transport of horseradish peroxidase (HRP) and with the fluorescent tracers Fast blue and rhodamine isothiocyanate (single and double labeling). Ascending and descending projections arise from the same laminae of the spinal grey except for neurons in contralateral lamina I and avian cervical Clarke's column which have ascending fibers only. A significant number of cervical nucleus proprius neurons (lamina IV) descends to the lumbar enlargement. Neurons with branching fibers were rare (less than 10 per cent).

Afferent Pathways↗

Response of neurons in the solitary tract nucleus, area postrema and lateral parabrachial nucleus to gastric load of hypertonic saline.

c-Fos was induced in the solitary tract nucleus (NTS), area postrema (AP) and lateral parabrachial nucleus (LPB) by the intragastric injection of hypertonic saline. The effect was bilateral and most dramatic in the NTS caudal to the facial nucleus and the AP, the areas receiving dense vagal afferent projection from the subdiaphragmatic structures. At least a part of these Fos-LI is considered to have been induced by the activation of the visceral osmoreceptors.

Animals↗

Spinal distribution and collateral projections of rat spinomesencephalic tract cells.

The distribution of cells belonging to the rat spinomesencephalic tract was studied by means of the retrograde transport of fluorescent dyes. Bilateral midbrain injections of cytoplasmic and nuclear tracers were made in order to evaluate the location of ipsilateral, contralateral, or bilaterally projecting cells. Spinal neurons with ascending projections to midbrain and descending propriospinal projections were identified by midbrain and spinal injections of different cytoplasmic labels. The locations of spinomesencephalic tract cells included seven regions of the spinal gray matter: marginal zone, lateral neck of the dorsal horn, nucleus proprius, the region around the central canal, the lateral cervical and spinal nuclei and the ventral horn. Cells projecting to the ipsilateral or contralateral midbrain had similar distributions and were frequently found in clusters with overlapping dendritic fields. Approximately 75% of spinomesencephalic cells projected to the contralateral midbrain. The largest contribution to the spinomesencephalic tract cell population was found in cervical cord segments 1-4. Cells with bilateral projections accounted for nearly 2% of all labeled cells, whereas 5% had both ascending and descending projections. Spinomesencephalic cells were found to have varying dendritic fields and morphology, e.g. fusiform, pyramidal, round/oval, and multipolar. The results of the present study lend further support to the view that the spinomesencephalic tract is a multi-component pathway with varied origins and projection targets.

Afferent Pathways↗

Spinal dorsal horn neuron response to mechanical stimuli is decreased by electrical stimulation of the primary motor cortex.

Motor cortex stimulation (MCS) has been used clinically as a tool for the control for central post-stroke pain and neuropathic facial pain. The underlying mechanisms involved in the antinociceptive effect of MCS are not clearly understood. We hypothesize that the antinociceptive effect is through the modulation of the spinal dorsal horn neuron activity. Thirty-two wide dynamic range spinal dorsal horn neurons were recorded, in response to graded mechanical stimulation (brush, pressure, and pinch) at their respective receptive fields, while a stepwise electrical stimulation was applied simultaneously in the motor cortex. The responses to brush at control, 10 V, 20 V, and 30 V, and recovery were 11.5+/-1.6, 12.1+/-2.6, 11.1+/-2.2, 10.5+/-2.1, and 13.2+/-2.5 spikes/s, respectively. The responses to pressure at control, 10 V, 20 V, and 30 V, and recovery were 33.2+/-6.1, 22.9+/-5.3, 20.5+/-5.0, 17.3+/-3.8, and 27.0+/-4.0 spikes/s, respectively. The responses to pinch at control, 10 V, 20 V, and 30 V, and recovery were 37.2+/-6.4, 26.3+/-4.7, 25.9+/-4.7, 22.5+/-4.3, and 35.0+/-6.2 spikes/s, respectively. It is concluded that, in the rat, electrical stimulation of the motor cortex produces significant transient inhibition of the responses of spinal cord dorsal horn neurons to higher intensity mechanical stimuli without affecting their response to an innocuous stimulus.

Action Potentials↗