Parallel pathways from motor and somatosensory cortex for controlling whisker movements in mice.

Mice can gather tactile sensory information by actively moving their whiskers to palpate objects in their immediate surroundings. Whisker sensory perception therefore requires integration of sensory and motor information, which occurs prominently in the neocortex. The signalling pathways from the neocortex for controlling whisker movements are currently poorly understood in mice. Here, we delineate two pathways, one originating from primary whisker somatosensory cortex (wS1) and the other from whisker motor cortex (wM1), that control qualitatively distinct movements of contralateral whiskers. Optogenetic stimulation of wS1 drove retraction of contralateral whiskers while stimulation of wM1 drove rhythmic whisker protraction. To map brainstem pathways connecting these cortical areas to whisker motor neurons, we used a combination of anterograde tracing using adenoassociated virus injected into neocortex and retrograde tracing using monosynaptic rabies virus injected into whisker muscles. Our data are consistent with wS1 driving whisker retraction by exciting glutamatergic premotor neurons in the rostral spinal trigeminal interpolaris nucleus, which in turn activate the motor neurons innervating the extrinsic retractor muscle nasolabialis. The rhythmic whisker protraction evoked by wM1 stimulation might be driven by excitation of excitatory and inhibitory premotor neurons in the brainstem reticular formation innervating both intrinsic and extrinsic muscles. Our data therefore begin to unravel the neuronal circuits linking the neocortex to whisker motor neurons.

Bilateral descending hypothalamic projections to the spinal trigeminal nucleus caudalis in rats.

Several lines of evidence suggest that the hypothalamus is involved in trigeminal pain processing. However, the organization of descending hypothalamic projections to the spinal trigeminal nucleus caudalis (Sp5C) remains poorly understood. Microinjections of the retrograde tracer, fluorogold (FG), into the Sp5C, in rats, reveal that five hypothalamic nuclei project to the Sp5C: the paraventricular nucleus, the lateral hypothalamic area, the perifornical hypothalamic area, the A11 nucleus and the retrochiasmatic area. Descending hypothalamic projections to the Sp5C are bilateral, except those from the paraventricular nucleus which exhibit a clear ipsilateral predominance. Moreover, the density of retrogradely FG-labeled neurons in the hypothalamus varies according to the dorso-ventral localization of the Sp5C injection site. There are much more labeled neurons after injections into the ventrolateral part of the Sp5C (where ophthalmic afferents project) than after injections into its dorsomedial or intermediate parts (where mandibular and maxillary afferents, respectively, project). These results demonstrate that the organization of descending hypothalamic projections to the spinal dorsal horn and Sp5C are different. Whereas the former are ipsilateral, the latter are bilateral. Moreover, hypothalamic projections to the Sp5C display somatotopy, suggesting that these projections are preferentially involved in the processing of meningeal and cutaneous inputs from the ophthalmic branch of the trigeminal nerve in rats. Therefore, our results suggest that the control of trigeminal and spinal dorsal horn processing of nociceptive information by hypothalamic neurons is different and raise the question of the role of bilateral, rather than unilateral, hypothalamic control.

Attack-related brainstem activation in a patient with SUNCT syndrome: an ictal fMRI study.

The authors report functional magnetic resonance imaging (fMRI) study data of a 60-year-old patient having short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing (SUNCT) syndrome. Three consecutive pain attacks were detected during the imaging session and strong brainstem activation was found. It was concluded that the brainstem can be involved in the pain signal transmission in SUNCT syndrome.

Modulatory effects of somatosensory electrical stimulation on neural activity of the dorsal cochlear nucleus of hamsters.

The effects of somatosensory electrical stimulation on the dorsal cochlear nucleus (DCN) activity of control and tone-exposed hamsters were investigated. One to three weeks after sound exposure and control treatment, multiunit activity was recorded at the surface of the left DCN before, during, and after electrical stimulation of the basal part of the left pinna. The results demonstrated that sound exposure induced hyperactivity in the DCN. In response to electrical stimulation, neural activity in the DCN of both control and exposed animals manifested four response types: S-S, suppression occurring during and after stimulation; E-S, excitation occurring during stimulation and suppression after; S-E, suppression occurring during stimulation and excitation after; and E-E, excitation occurring during and after stimulation. The results showed that there was a higher incidence of suppressive (up to 70%) than of excitatory responses during and after stimulation in both groups. In addition, there was a significantly higher degree of suppression after, rather than during stimulation. At high levels of electrical current, the degree of the induced suppression was generally higher during and after stimulation in exposed animals than in controls. The similarity of our results to those of previous clinical studies further supports the view that DCN hyperactivity is a direct neural correlate of tinnitus and that somatosensory electrical stimulation can be used to modulate DCN hyperactivity. Optimization of stimulation strategy through activating only certain neural pathways and applying appropriate stimulation parameters may allow somatosensory electrical stimulation to be used as an effective tool for tinnitus suppression.

Somatotopic activation in the human trigeminal pain pathway.

Functional magnetic resonance imaging was used to image pain-associated activity in three levels of the neuraxis: the medullary dorsal horn, thalamus, and primary somatosensory cortex. In nine subjects, noxious thermal stimuli (46 degrees C) were applied to the facial skin at sites within the three divisions of the trigeminal nerve (V1, V2, and V3) and also to the ipsilateral thumb. Anatomical and functional data were acquired to capture activation across the spinothalamocortical pathway in each individual. Significant activation was observed in the ipsilateral spinal trigeminal nucleus within the medulla and lower pons in response to at least one of the three facial stimuli in all applicable data sets. Activation from the three facial stimulation sites exhibited a somatotopic organization along the longitudinal (rostrocaudal) axis of the brain stem that was consistent with the classically described "onion skin" pattern of sensory deficits observed in patients after trigeminal tractotomy. In the thalamus, activation was observed in the contralateral side involving the ventroposteromedial and dorsomedial nuclei after stimulation of the face and in the ventroposterolateral and dorsomedial nuclei after stimulation of the thumb. Activation in the primary somatosensory cortex displayed a laminar sequence that resembled the trigeminal nucleus, with V2 more rostral, V1 caudal, and V3 medial, abutting the region of cortical activation observed for the thumb. These results represent the first simultaneous imaging of pain-associated activation at three levels of the neuraxis in individual subjects. This approach will be useful for exploring central correlates of plasticity in models of experimental and clinical pain.

Parallel streams for the relay of vibrissal information through thalamic barreloids.

This study investigated the organization of a vibrissal pathway that arises from the interpolar division of the spinal trigeminal complex (SP5i), transits through the ventral posterior medial nucleus (VPM), and innervates the somatosensory cortical areas in the rat. Using Fluoro-Gold and biotinylated dextran amine, respectively, as retrograde and anterograde tracers, the following organization plan was disclosed. The SP5i projection arises from a population of small-sized neurons that selectively innervate the ventral lateral part of VPM. In cytochrome oxidase-stained material, this region does not display any barreloid arrangement, but Fluoro-Gold injections in single barrel columns labeled rods of cells that extend caudally into the ventral lateral division of VPM. Thus, on the basis of retrograde labeling, barreloids were divided into core and tail compartments, which correspond to the rod segments running across the dorsal and ventral lateral parts of VPM, respectively. Double-labeling experiments revealed that SP5i afferents innervate the tail of barreloids. The anterograde labeling of thalamocortical axons show that most "core cells" project to a single barrel column, whereas some "tail cells" give rise to branching axons that innervate the second somatosensory area and the dysgranular zone of the barrel field. Injections that straddled the transition zone between the core and tail regions disclosed cells projecting to a single barrel column and to the surrounding dysgranular zone. These results suggest that the projection of "barreloids cells" to the granular and/or dysgranular zones relates to the class of prethalamic input(s) they receive.

Projections from subnucleus oralis of the spinal trigeminal nucleus to contralateral thalamus via the relay of juxtatrigeminal nucleus and dorsomedial part of the principal sensory trigeminal nucleus in the rat.

Following injection of HRP into contralateral thalamus, retrogradely labeled cells were observed in principal sensory trigeminal nucleus (Vp) and an area of juxtatrigeminal nucleus (JX) formerly described by John and Tracey (1987). When PHA-L was delivered to dorsomedial part of the subnucleus oralis (Vodm), PHA-L labeled terminals were seen in dorsomedial part of the Vp (Vpdm) and in the JX region. Comparing the distribution of PHA-L labeled terminal field with that of HRP labeled JX neurons showed that the labeled terminals and neurons were overlapped closely in the JX. The distribution patterns of the labeled terminals and JX neurons were also the same: viewed on the coronal planes caudal-rostrally, both of the labelings began to appear at the levels where the facial nerve root was just broken. Rostrally, at middle levels of the motor trigeminal nucleus (Vmo), the labelings showed their typical view covering dorsal and ventral JX (dJX, vJX). The labelings disappeared at rostral poles of the Vmo and Vp. When injections of PHA-L into the Vodm and HRP into the contralateral thalamus was made in one rat, the contacts between Vodm projecting terminals labeled with PHA-L and HRP labeled trigemino-thalamic neurons were seen in the JX and also in the Vpdm. Then, electron microscopic (EM) study was done, injections of kainic acid into the Vodm and HRP into the contralateral thalamus was performed simultaneously. After EM embedding, the JX and Vpdm regions were selected, ultrathin sections were cut and observed with EM. In both areas, axo-somatic and axo-dendritic synapses were seen between degenerated boutons and HRP labeled somata or dendrites. Namely, the Vodm projecting terminals synapsed on trigemino-thalamic neurons in the JX and Vpdm. Anyway, axo-dendritic synapses was the main type of observed synapses. Thus, the present work demonstrated 1. the JX containing a group of trigemno-thalamic neurons was a target of special projections froin the Vodm; 2. The Vodm neurons projected to the contralateral thalamus through the relay of JX and Vpdm neurons.

Distribution of nitric oxide synthase-immunoreactive interneurons in the spinal trigeminal nucleus.

The spinal trigeminal nucleus is involved in the transmission of orofacial sensory information. Neither the distribution of the neuromessenger, nitric oxide, within the trigeminal system nor the possible relationship of this simple gas with trigeminothalamic neurons has been carefully studied. Using immunocytochemical (against nitric oxide synthase) and histochemical (NADPH-diaphorase staining) techniques, we have found that nitric oxide neurons and processes are more prominent in the nucleus caudalis and the dorsomedial aspect of the nucleus oralis than in other spinal trigeminal regions. To study the relationship of nitric oxide to trigeminothalamic neurons and intertrigeminal interneurons of the spinal trigeminal nucleus, spinal trigeminal neurons were retrogradely labeled with fluorogold by thalamic injections or by injections into the junction of the nucleus interpolaris and nucleus caudalis. Medullary sections were subsequently processed with NADPH-diaphorase histochemistry. None of the diaphorase-stained neurons in the spinal trigeminal nucleus was found to contain fluorogold; however, some diaphorase-stained processes were found in close proximity to trigeminothalamic neurons. Following spinal trigeminal nucleus injections, many diaphorase-stained neurons were found to contain fluorogold, especially in the nucleus caudalis, suggesting that nitric oxide-containing neurons in the spinal trigeminal nucleus are intertrigeminal interneurons. Collectively, these data indicate that nitric oxide is most prominent in interneurons located in nucleus caudalis and that these interneurons give rise to processes that appose trigeminothalamic neurons, raising the possibility that they may indirectly influence orofacial nociceptive processing at the level of the spinal trigeminal nucleus via nitric oxide production.

Integration in trigeminal premotor interneurones in the cat. 1. Functional characteristics of neurones in the subnucleus-gamma of the oral nucleus of the spinal trigeminal tract.

The profile of integration in a sample of 183 interneurones localized in the subnucleus-gamma of the oral nucleus of the spinal trigeminal tract (NVspo-gamma) has been analyzed. 134 neurones were tested for inputs from primary afferents of the trigeminal, facial and cervical nerves as well as for inputs from the midbrain and from the cervical spinal cord. The remaining 49 neurones were tested for inputs from the primary afferents and for descending convergence from defined sites within the oro-facial primary projections of the cerebral cortex. It was found that the interneurones, mainly recorded in the dorsal and dorsomedial aspect of the NVspo-gamma, receive short latency inputs from the low threshold oral and perioral afferents and longer latency inputs from the high threshold jaw and neck muscle afferents. There was evidence for convergence from the cervical segmental level (29%) and some of the neurones had axon terminals in the superior colliculus. However, the interneurones did not receive a descending tectal input. About 80% of the NVspo-gamma interneurones were activated from the orofacial primary projection fields within cytoarchitectonic areas 3a and 3b of the coronal gyrus. This input was topographically organized and the neurones were activated from the same oral and perioral region of the periphery as the cortical region from which the descending projections themselves originated. Minimum latencies indicated a monosynaptic connection. The convergence profile onto the NVspo-gamma interneurones appeared unique as compared with interneurones located in the intertrigeminal area. Aspects of the possible functional roles of the NVspo-gamma neurones are discussed in relation to ongoing oro-facial ("masticatory") movements. The properties of a selected sample of NVspo-gamma interneurones, which were antidromically activated from the digastric subnucleus of the trigeminal motor nucleus, are reported in a companion paper (Olsson and Westberg 1991).

Ultrastructural and neurochemical analysis of synaptic input to trigemino-thalamic projection neurones in lamina I of the rat: a combined immunocytochemical and retrograde labelling study.

The synaptology of lamina I thalamic projection neurones in the spinal trigeminal nucleus of the rat was investigated by combining electron microscopic immunocytochemistry with the retrograde transport of horseradish peroxidase. Fifteen retrogradely labelled neurones were serially sectioned and their dendrites were traced for up to 160 microns in order to characterise the synaptic input to their cell bodies and proximal dendrites. Projection neurones receive synapses from dome-shaped substance P and enkephalin immunoreactive terminals, which make simple axosomatic or axodendritic synapses. In addition, the cells receive synapses from numerous nonimmunoreactive terminals including a wide range of different dome-shaped terminals and various scalloped or glomerular terminals. Dome-shaped terminals synapse with small stubby spines in addition to cell bodies or dendritic shafts and they are probably derived from lamina II interneurones and from descending bulbospinal pathways. Glomerular terminals occur in two main classes: small type A terminals with dark axoplasm and larger type B terminals. Type B terminals participate in synaptic triads in which a peripheral terminal synapses both axoaxonically with the glomerular terminal and axodendritically with the projection neurone. Type A and type B terminals closely resemble the central terminals of spinal cord lamina II glomeruli and are probably derived from C and A delta I degrees afferent fibers. The results indicate that lamina I projection neurones are under pre- and postsynaptic control from diverse sources. Their complex synaptic organisation highlights the key role that such cells play in the rostrad transmission of somatosensory information.

The spinothalamic system of the rat. I. Locations of cells of origin.

Horseradish peroxidase retrograde transport has been used to locate neurons of the rat spinal cord and lower medulla that project to the thalamus. Eight groups of spinothalamic cells are identified, some of which are anatomically continuous with thalamically projecting groups in the lower medulla. Most of the groups are seen only at the highest cervical levels, and several of them have not been previously recognised as spinothalamic relays. They are marginal layer (M), ventral border of the substantia gelatinosa (SGv), neck of the dorsal horn (N), lateral cervical nucleus (LCN), ventromedial portion of the dorsal horn (DHvm), intermediate gray zone (IGZ), dorsal portion of the ventral horn (VHd), and ventral portion of the ventral horn (VHv). Most of the cell bodies are contralateral to their thalamic terminations; only the VHd group is ipsilateral. The major finding conflicts with traditional concepts of the spinothalamic system, and concerns the rostrocaudal distribution of the cells of origin. With the sole exception of the DHvm group, the great majority of the thalamically projecting neurons of the rat are confined to the most rostral spinal levels (medulla/cord junction through C4). Below C4, most of the spinothalamic cells are concentrated in a single DHvm group between levels T9 and L4, probably concerned with hindlimb proprioception. The spinothalamic groups at high cervical levels may be relays for information ascending from lower regions. This might help to explain why, in man, surgical destruction of fibres crossing the midline in a single high cervical segment can cause a loss of pain sensation over most of the body.

Implication of the spinal nucleus of the trigeminal nerve in acupuncture.

This voluminous nucleus extends from the upper part of the medulla oblongata to the 4th cervical segment of the spinal cord. This topography puts it in relation with numerous other spinal and cerebral centers = ventral and dorsal horns of the spinal cord, including spinal nucleus of the accessory nerve, nucleus solitarius, motor dorsal nucleus of the vagus nerve, reticular formation, etc... Even if the longitudinal aspect of this nucleus is not uniform, it must be pointed out that the three branches of the trigeminal nerve are represented along this course through the trigeminal spinal tract. These relations explain the straight reciprocal action of the nerve areas of the trigeminal branches with the first four cervical nerves and the related autonomic links. These direct elementary reflexes may explain: many referred symptoms; etiologic or triggering factors of neuralgias in the entire cervico-cephalic region; the treatment of the cervico-cephalic diseases (of cerebrospinal or autonomic type) by stimulation of the various cervico-cephalic structures: acupuncture points, articular manipulations, massages, etc... an important part of auriculopuncture effects; the possibility to use points localized in various nerve areas to get the same action.

Cytoarchitectonic coincidence with the discontinuous connectional pattern in the deep layers of the superior colliculus in the rat.

The aims of the present study are to demonstrate cytoarchitectonically columnar structures in the deep layers of the rat's superior colliculus, and to show experimentally the existence of a clear correlation between the cytoarchitectonically defined columnar structures and the discontinuous patterns of the tectal connections in the deep layers. Injections of horseradish peroxidase conjugated to wheat germ agglutinin (HRP-WGA) into the prefrontal cortex produced orthograde labeling in the columnar structures in the deep layers of the superior colliculus, while HRP-WGA injections into the somatic sensory cortex resulted in orthograde labeling in the areas outside the columnar structures, so that the distribution patterns of terminals from these two different cortical areas are complementary in the deep layers. Cells of origin of the tectal efferents are also differentiated in terms of the columnar structures; HRP-WGA injections into the dorsal medial nucleus of the thalamus yielded retrograde labeling of spindle-cells within the columns, whereas the injections into the trigeminal sensory nuclei produced retrograde labeling of polygonal cells in the areas outside of the columns. These results suggest that as in the dorsoventral laminar coincidence with the tectal connections, there is a well organized mediolateral registration of the tectal connections with the cytoarchitectonically defined cell arrangement in the deep layers of the superior colliculus.

Ascending and descending internuclear connections of the trigeminal sensory nuclei in the cat. A study with the retrograde and anterograde horseradish peroxidase technique.

The distribution of cells of origin of ascending and descending internuclear connections in the trigeminal sensory nuclei was studied by the retrograde horseradish peroxidase technique in the cat. The termination of collaterals of these ascending axons was also studied by the anterograde transport of horseradish peroxidase. Following injections of horseradish peroxidase into the ventral part of the principal sensory nucleus and the adjacent reticular formation many small neurons were labeled ipsilaterally in the whole area of the caudal portion of the nucleus interpolaris and in laminae III and IV of the nucleus caudalis. Labeled neurons were also found in laminae I and V. Injections limited to either nucleus oralis, the ventral part of the principal sensory nucleus and the medial parabrachial nucleus labeled similar types of neurons in the above regions with a topographic relationship; neurons in the dorsal part of the nuclei caudalis and interpolaris project, dorsally, to rostral portions of the trigeminal sensory nuclei while those in the ventral part of the nuclei caudalis and interpolaris project ventrally. Anterograde labeling of axons arising from the nucleus caudalis demonstrates that the axons ascend in the intranuclear bundles and the adjacent reticular formation, and give off collaterals to the nuclei interpolaris and oralis, and the ventral part of the principal sensory nucleus. Injections limited to the nucleus caudalis labeled small neurons in the rostral portion of the nucleus oralis and the caudal portion of the nucleus interpolaris. The present study suggests that these ascending and descending internuclear connections of the trigeminal sensory nuclei may modulate transmission of afferent inputs to various projection sites, such as thalamus, superior colliculus, cerebellum and spinal cord.