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.     

Pulpar tooth injury induces plastic changes in S100B positive astroglial cells in the trigeminal subnucleus caudalis

Pain in humans constitutes a complex perception that involves peripheral tissues, nerves and the central nervous system. The glia is thought to be involved in the propagation and modulation of painful stimuli, as well as for the neurotransmission and plastic changes. In this work, an intermediate inflammatory nociceptive stimulus was generated after the exposure of the pulp in the left mandibular first molar. We analyzed the relationship between this tooth injury and the S100B expression in the trigeminal subnucleus caudalis. A significant difference of S100B immunoreactivity between the ipsilateral and the contralateral side could be observed at the 4th postoperative day. Besides, S100B positive-astrocytes located in the ipsilateral side showed an increase in their arborization, but not in the level of expression of the S100B protein. Our findings suggest that a unilateral peripheral nociceptive stimulus produces modifications in S100B positive-astrocytes in both sides of the trigeminal subnucleus caudalis.     

Hypothalamic control of nocireceptive and other neurones in the marginal layer of the dorsal horn of the medulla (trigeminal nucleus caudalis) in the rat

Summary The effect of electrical stimulation of the preoptic area of the hypothalamus on the discharge of neurones in the marginal layer (lamina I) of the trigeminal nucleus caudalis was studied in the anaesthetised rat. There was a powerful suppression of the discharge evoked by noxious thermal stimuli in 49/49 specific nociceptor driven (nocireceptive) neurones. The inhibitory effect increased with graded increases in the intensity of preoptic stimulation. Stimulation, however, produced only a small reduction in the discharge of 14/17 cold receptive neurones. Thresholds for producing suppression of cold receptive neurones were generally higher than those for nocireceptive neurones. There was no effect on the activity of 12/12 low threshold mechanoreceptive neurones. The inhibitory action generated on the activity of nocireceptive neurones was reduced by electrolytic lesions in the nucleus raphe magnus (NRM) or the nucleus paragigantocellularis lateralis (PGCL) or the dorsolateral and ventrolateral periaqueductal gray matter (PAG). Lesions made in the ventral or dorsal aspect of PAG were, however, ineffective in reducing the suppression. It is suggested that the powerful descending inhibitory control of nociceptive transmission in the trigeminal nucleus caudalis is one of the neuronal mechanisms mediating analgesia from the preoptic area of the hypothalamus.     

Morphology and synaptic connections of unmyelinated primary axons in the border zone of rat trigeminal nucleus oralis

This anterograde horseradish peroxidase study examines the morphology and synaptic connections of a population of primary axons which terminate in the dorsal one-half of the border zone (BZ) of rat trigeminal nucleus oralis. Unmyelinated parent fibers in the spinal V tract enter BZ directly and each terminate by continuing as a sparsely branched, long caudally directed strand containing several axonal endings. Primary endings lie in glomeruli where each forms an asymmetrical synapse on a central dendrite. Other glomerular components include two types of non-primary endings. One contains flattened synaptic vesicles, and forms a symmetrical synapse on either the primary ending or the central dendrite, while the other contains pleomorphic synaptic vesicles and establishes a symmetrical synapse on the central dendrite.     

Centralis superior raphe, reticularis pontis nuclei, and sleep-wakefulness cycle in cats

This study examines the influence of lesions in the centralis superior raphe nucleus (CeSR) and adjacent paramedial pontine tegmentum on the sleep/wakefulness cycle (SWC) in cats. Sixteen cats had electrodes implanted for electro-oculogram (EOG), electromyogram (EMG), electroencephalogram (EEG) and ponto-geniculo-occipital (PGO) recordings. There were 10 experimental animals: seven animals received diathermocoagulation lesions destroying between 7 and 27% of the CeSR; the remaining three cats suffered bilateral lesions in the paramedial portion of the reticularis pontis oralis (RPO) and caudalis (RPC) nuclei. Six sham-operated animals were used as controls. Recordings were taken of all animals in continuous 23-h sessions once a week for 12 weeks. Results indicated that the threshold for SWC state changes (increase of wakefulness (W) and drowsiness (D), and decrease of slow wave sleep (SWS)) after CeSR lesion is approximately 11.3% following volumetric destruction of the nucleus. The amount of CeSR damage (CeSR-D) only correlated significantly with the amount of W (positive correlation) and SWS (negative correlation) during the first week post-lesion. The changes in W over the course of the study were different in the two experimental groups. In both groups, total W was increased with respect to the controls, however, these increases were observed earlier in the CeSR-D group. The return to near control values in SWC state over days 15–28 of the study does not represent a definitive recovery by the CeSR-D cats. All the SWC states returned to control values by the tenth week in the cats with paramedial reticular pontine damage.     

Chordin and noggin expression in the adult rat trigeminal nuclei

Bone morphogenetic proteins (BMP) exert its biological functions by interacting with membrane bound receptors. However, functions of BMPs are also regulated in the extracellular space by secreted antagonistic regulators, such as chordin and noggin. Although the deep involvement of BMP signaling in the development and functions of the trigeminal nuclei has been postulated, little information is available for its expression in the trigeminal nuclei. We, thus, investigated chordin and noggin expression in the adult rat trigeminal nuclei using immunohistochemistry. Chordin and noggin were intensely expressed throughout the trigeminal nuclei. In addition, interesting differences are observed between chordin expression and noggin expression. For example, chordin prefers dendritic expression than noggin, suggesting that chordin is involved in the regulation of dendritic morphology and synaptic homeostasis. Furthermore, chordin and noggin were differentially expressed in the neuropil of the trigeminal nuclei. Since BMP signaling is known to play a pivotal role to make precise neural network, theses differences might be important to keep precise interneuronal connections by regulating local BMP signaling intensity in each region. Interestingly, we also detected chordin and noggin expression in axons of the trigeminal nerves. These data indicate that chordin and noggin play pivotal roles also in the adult trigeminal system.     

Respiratory effects of sensorimotor cortex and their mechanisms in rats

Acute experiments on anesthetized rats showed differential effect of various areas of the sensorimotor cortex on activity of the respiratory center. It is hypothesized that GABAergic structures of the solitary tract nucleus play an important role in the mechanisms of respiratory effects of the sensorimotor cortex.     

Collateral projections of trigeminal ganglion neurons to both the principal sensory trigeminal and the spinal trigeminal nuclei in the rat

Employing a combination of fluorescent retro grade double labelling and immunofluorescence histo chemistry for substance P (SP) and calcitonin gene-relat ed peptide (CGRP), we examined collateral projections from single neurons in the trigeminal ganglion (TG) of the rat to both the principal sensory trigeminal nucleus (Vp) and the oral, interpolar or caudal subnuclei of the spinal trigeminal nucleus (Vo, Vi or Vc). In the rats that were unilaterally injected with fast blue (FB) into the Vp and with diamidino yellow (DY) into the Vo, Vi or Vc, neurons labelled with FB and/or DY were observed in the TG ipsilateral to the injections. Of the labelled TG neurons, about 2% were double labelled with both trac ers in the rats that were injected with FB into the Vp and with DY into the Vo or Vi, and about 10% were double labelled in the rats that were injected with FB into the Vp and with DY into the Vc. The results indicate that TG neurons sending their axons to the Vp project, by way of axon collaterals, to the Vc more frequently than to the Vo or Vi.Some of the TG neurons double labelled with FB and DY exhibited SP-or CGRP-like immunoreactivity (LI): Of the TG neurons that were double labelled with FB injected into the Vp and with DY injected into the Vo, Vi or Vc, about 38%, 49% and 42%, respectively, displayed SP-LI, and about 54%, 58% and 59%, respectively, showed CGRP-LI. Some of the SP-or CGRP-LI TG neurons that were double labelled with FB and DY were assumed to mediate pain signals to both the Vp and the spinal trigeminal nucleus (Vo, Vi and/or Vc) by way of axon collaterals.Yun-Qing Li is on leave from the Department of Anatomy, The Fourth Military Medical University, Xian, People's Republic of China     

The efferent connections of the nuclei of the descending trigeminal tract in the mallard (Anas platyrhynchos L.)

The efferent and intranuclear connections of the nuclei of the descending trigeminal tract of the mallard have been studied with lesion methods, and by axonal transport techniques following injections of tritiated leucine, and of horseradish peroxidase.The large subnucleus oralis neurons, including those belonging to the nucleus of the ascending glossopharyngeal tract, have proven to be the sole origin of trigeminocerebellar connections. The cerebellar afferents are of the mossy fiber type, and terminate predominantly in lobules V, VI and VII, and possibly, lobule IV. Trigeminocerebellar projections are ipsilateral except for the vermal area.Subnucleus interpolaris is the main source of intratrigeminal fibers that terminate in subnucleus oralis and the ventral part of the main sensory nucleus. These intranuclear connections are bilateral, but the medium-celled caudal part of subnucleus interpolaris in particular contains the majority of bi- and/or contralaterally projecting neurons. Additionally, the small cells in the rostral part of subnucleus interpolaris project ipsilaterally upon the parabrachial region, and upon the lateral reticular formation.Projections upon the parabrachial region furthermore emanate bilaterally from layer I of the rostral subnucleus caudalis. A minor part of layer I neurons sends its axons contralaterally along with those of the dorsal column nuclei toward the thalamic nucleus dorsolateralis posterior. Associated with the medial lemniscus, contralateral termination is also present in the lateral part of the ventral lamella of oliva caudalis, in the marginal zone of nucleus mesencephalicus lateralis, pars dorsalis and immediately surrounding intercollicular grey and, finally, in the nucleus intercalatus thalami. Furthermore, a bilaterally descending projection from subnucleus caudalis upon layers I and II of the rostral cervical cord was observed. Close to their origin subnucleus caudalis neurons project upon the adjoining caudal part of the lateral reticular formation.     

Excitatory amino acid binding sites in the trigeminal principal sensory and spinal trigeminal nuclei of the rat.

Quantitative autoradiography was used to examine the density and distribution of excitatory amino acid (EAA) binding site subtypes in the principal sensory and spinal trigeminal nuclei of the rat trigeminal complex. The highest densities of N-methyl-D-aspartate (NMDA), alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA), kainate and metabotropic receptors were found in the superficial laminae (I and II) of subnucleus caudalis, a region known to be densely innervated by primary afferent nociceptive terminals. Lower densities of EAA binding sites were observed in spinal subnuclei interpolaris and oralis and within the principal sensory nucleus. These results are consistent with the hypothesis that EAAs are involved in primary afferent nociceptive neurotransmission.     

The distribution of binding by isolectin I-B4 from Griffonia simplicifolia in the trigeminal ganglion and brainstem trigeminal nuclei in the rat.

The distribution of binding by the isolectin I-B4 from Griffonia simplicifolia in the rat trigeminal system has been investigated. This lectin binds to a sub-population of small-diameter trigeminal ganglion neurons. Double-labelling studies revealed that this lectin bound to all the trigeminal ganglion neurons containing somatostatin, whereas it bound to less than 25% of those containing calcitonin gene-related peptide or substance P. In the brainstem this lectin gave terminal-like staining in only the sub-nucleus caudalis of the trigeminal nuclei. In this nucleus, staining was most dense in the inner part of lamina II. Morphometric studies suggest that this lectin and that from the soybean recognize the same population of cells. The relationship of this data to those obtained in other studies using markers binding to glycoconjugates with a terminal alpha-galactose is discussed.     

The cells of origin of the trigeminothalamic,trigeminospinal and trigeminocerebellar projections in the cat

Using the retrograde horseradish peroxidase technique, we have examined the distribution of labeled thalamic-, spinal- and cerebellar-projecting neurons in the trigeminal sensory nuclei of the cat.Injections into the nucleus ventralis posterior of the thalamus resulted in labeling of neurons in lamina I (subnucleus zonalis), the deeper part of lamina IV (the subhucleus magnocellularis) of the nucleus caudalis and in lamina V (the lateral extension of the nucleus medullae oblongatae centralis) on the contralateral side. A very large number of labeled small neurons were observed mainly in the caudal part of the nucleus interpolaris and in the ventral division of the principal sensory nucleus on the contralateral side and in the dorsal division of the principal sensory nucleus on the ipsilateral side.Injections into the known projection areas of the cerebellar cortex labeled mainly ipsilaterally the trigeminocerebellar neurons in a restricted ventrolateral area of lamina IV of the nucleus caudalis at its rostral level and in lamina V. Many labeled neurons were also observed in the nucleus interpolaris. Although the distribution overlapped with that of the trigeminothalamic neurons, the greatest majority were concentrated in its rostral part where the trigeminothalamic neurons were very small in number. In addition, labeled neurons were observed in the rostral part of the nucleus oralis and the ventralmost part of the ventral division of the principal sensory nucleus. No labeled neurons were observed in the dorsal division of the principal sensory nucleus and the mesencephalic nucleus.The trigeminospinal neurons were labeled mainly ipsilaterally following injections into the upper cervical cord. They were located in laminae I and III, the deeper part of lamina IV of the nucleus caudalis and in lamina V. Only scattered labeled neurons were found in the nucleus interpolaris. The number of labeled neurons increased in the nucleus oralis at the level of the superior olive. They tended to be distributed around or dorsal to the groups of the trigeminothalamic neurons at the caudal part of the principal sensory nucleus. No neurons of the principal sensory nucleus appeared to project to the spinal cord. Based on the large size and location, the trigeminospinal neurons could be differentiated from the other projection neurons in the nucleus oralis.The present study demonstrates that the trigeminal sensory nuclei are composed of groups of neurons with different projections, since the main aggregations are localized at different levels. However, it should be examined whether the neuronal groups, which are labeled from the different structures in similar locations, are composed of individual neurons projecting to more than one of these structures.     

The morphology of neurons in trigeminal nucleus oralis projecting to the medullary dorsal horn (trigeminal nucleus caudalis): a retrograde horseradish peroxidase and Golgi study

This study demonstrates that trigeminal nucleus oralis, the most rostral subdivision of the spinal trigeminal nucleus, contains four morphologically distinct types of small neurons which project to the medullary dorsal horn (trigeminal nucleus caudalis) via descending intratrigeminal pathways. Using the retrograde transport of horseradish peroxidase following injections in the medullary dorsal horn, labeled small neurons with cell bodies ranging from 8-15 microns in diameter are found principally in the ventrolateral portion of the trigeminal nucleus oralis. Most neurons are labeled ipsilaterally throughout the entire rostrocaudal extent of the ventrolateral portion of the trigeminal nucleus oralis, but a few cells are also labeled contralaterally. From this aspect of the present study it can be concluded that a specific portion of the trigeminal nucleus oralis, i.e. the ventrolateral part, contains numerous small neurons which send descending projections to the medullary dorsal horn that could affect synaptic activity there. Utilizing both the methods of Golgi and retrograde horseradish peroxidase labeling four distinct types of small descending medullary dorsal horn projection neurons can be distinguished in the ventrolateral portion of the trigeminal nucleus oralis on the basis of their morphology and the distribution of their axons and dendrites. All four neuronal cell types are present throughout the entire rostrocaudal extent of the trigeminal nucleus oralis. Type I neurons are the most frequently labeled descending medullary dorsal horn projection neurons. They are concentrated in the medial 500-550 microns of the ventrolateral portion of the trigeminal nucleus oralis and display dendritic trees which occupy spherical domains approaching 300 microns in diameter. The unmyelinated axons of many of these cells arise either directly from the cell body or a primary dendrite and give rise to a single collateral within 50 microns of their site of origin. This collateral generates a fine axonal plexus within a portion of the dendritic arbor of the parent cell while the parent axon, without branching further, travels a short distance in the ventrolateral portion of the trigeminal nucleus oralis and enters a deep axon bundle. Type II neurons are the second most frequently labeled descending medullary dorsal horn projection neuron. They generate medial and lateral dendritic arbors which together span nearly the entire medial 500-550 microns of the ventrolateral portion of the trigeminal nucleus oralis. An unmyelinated axon emerges from the cell body and within 10-30 microns of its origin gives rise to two collaterals.(ABSTRACT TRUNCATED AT 400 WORDS)     

Induction of c-Fos-like protein in bulbar catecholaminergic neurones by electrical stimulation of the sensorimotor cortex in the rat

The sensorimotor cortex (SMC) establishes a functional connectivity with the nucleus tractus solitarius (NTS) and the rostral ventrolateral medulla (RVLM). These bulbar nuclei are known to contain catecholaminergic neurones involved in the cardiovascular control. The aim of the present study was to establish the proportion of catecholaminergic neurones activated by electrical stimulation of SMC. For this purpose, double immunocytochemical procedures were used to reveal the distribution of Fos protein and tyrosine hydroxylase (TH). The results showed that, in the NTS, 7% of the neurones immunoreactive for TH expressed Fos-protein, versus 34% in the RVLM. These data provide evidence that the SMC activated preferentially catecholaminergic neurones of the RVLM which are known to be involved in cardiovascular control via spinal preganglionic neurones.     

N-methyl-D-aspartate receptor-independent long-term depression and depotentiation in the sensorimotor cortex of the freely moving rat

Bidirectional modifications in synaptic efficacy are central components in recent models of cortical learning and memory, and we previously demonstrated both long-term synaptic potentiation (LTP) and long-term synaptic depression (LTD) in the neocortex of the unanaesthetized adult rat. Here, we have examined the effects of N-methyl-D-aspartate receptor (NMDAR) blockade on the induction of LTD, LTP, and depotentiation of field potentials evoked in sensorimotor cortex by stimulation of the white matter in the adult, freely moving rat. High frequency (300 Hz) stimulation (HFS) was used to induce LTP and prolonged, low-frequency (1 Hz) stimulation was used to induce either depotentiation or LTD. LTD was expressed as a reduction in the amplitude of the short and long-latency field potential components, while depotentiation was expressed as a decrease in the amplitude of a previously enhanced late component. Under NMDAR blockade, HFS failed to induce LTP and instead produced a depression effect similar to LTD. Following washout of the drug, HFS induced a normal LTP effect. Unlike LTP, LTD and depotentiation were found to be NMDAR-independent in the neocortex of the freely moving rat.     

High- and low-threshold calcium currents in neurons acutely isolated from rat sensorimotor cortex

Neurons were isolated by papain treatment and trituration of the frontoparietal cortex of 14 to 28-day-old rats. Whole cell voltage clamp revealed a slowly inactivating high-threshold Ca²⁺ current, activated positive to −45 mV, and a transient low-threshold Ca²⁺ current, activated positive to −65 mV. The high-threshold current was more sensitive to block by Cd²⁺ and the low-threshold current was more sensitive to block by Ni²⁺. Replacement of Ca²⁺ by Ba²⁺ increased the high-threshold current and reduced the low-threshold current. The high-threshold current was enhanced by Bay K 8644 and reduced by nimodipine and ω-conotoxin. The low-threshold current was also reduced by nimodipine but was insensitive to Bay K 8644 and ω-conotoxin. The properties of the currents were consistent with different underlying Ca²⁺ channel types.     

Interactions between LTP- and LTD-inducing stimulation in the sensorimotor cortex of the awake freely moving rat

Bidirectional modifications in synaptic efficacy are central components in models of cortical learning and memory. More recently, the regulation of synaptic plasticity according to the history of synaptic activation, termed "metaplasticity," has become a focus of research on the physiology of memory. Here we explore such interactions between long-term potentiation (LTP) and long-term depression (LTD) in the chronically prepared rat. The effects of successive high- and low-frequency stimulation were examined in sensorimotor cortex in the adult, freely moving rat. High-frequency (300 Hz) stimulation (HFS) applied to the white matter was used to induce LTP, and prolonged, low-frequency (1 Hz) stimulation (LFS) was used to induce either depotentiation or LTD. Combined stimulation (HFS/LFS or LFS/HFS) during the induction phase attenuated potentiation effects only if the LFS followed the HFS. LTD induced by LFS alone was expressed as a reduction in the amplitude of both short- and long-latency field potential components, whereas depotentiation was primarily expressed as a decrease in the amplitude of the potentiated long-latency component. In other experiments, LTP (or LTD) was induced to asymptotic levels before applying LFS (or HFS). LFS caused depotentiation of the late component but had no measurable effect on the early component. HFS reversed previously induced LTD, but the potentiation decayed more rapidly than usual. LTP and LTD therefore modulate each other in the awake, behaving rat.     

Coherent spike-wave oscillations in the cortex and subthalamic nucleus of the freely moving rat

The basal ganglia play a critical role in controlling seizures in animal models of idiopathic non-convulsive (absence) epilepsy. Inappropriate output from the substantia nigra pars reticulata (SNr) is known to exacerbate seizures, but the precise neuronal mechanisms underlying abnormal activity in SNr remain unclear. To test the hypothesis that cortical spike-wave oscillations, often considered indicative of absence seizures, propagate to the subthalamic nucleus, an important afferent of SNr, we simultaneously recorded local field potentials from the frontal cortex and subthalamic nucleus of freely moving rats. Spontaneous spike-wave oscillations in cortex (mean dominant frequency of 7.4 Hz) were associated with similar oscillations in the subthalamic nucleus (mean of 7.9 Hz). The power of oscillations at 5-9 Hz was significantly higher during spike-wave activity as compared with rest periods without this activity. Importantly, spike-wave oscillations in cortex and subthalamic nucleus were significantly coherent across a range of frequencies (3-40 Hz), and the dominant (7-8 Hz) oscillatory activity in the subthalamic nucleus typically followed that in cortex with a small time lag (mean of 2.7 ms). In conclusion, these data suggest that ensembles of subthalamic nucleus neurons are rapidly recruited into oscillations during cortical spike-wave activity, thus adding further weight to the importance of the subthalamic nucleus in absence epilepsy. An increase in synchronous oscillatory input from the subthalamic nucleus could thus partly underlie the expression of pathological activity in SNr that could, in turn, aggravate seizures. Finally, these findings also reiterate the importance of oscillations in these circuits in normal behaviour.