Extracellular glutamate, aspartate and arginine increase in the ventral posterolateral thalamic nucleus during nociceptive stimulation

Although there is evidence that the thalamus plays a remarkable role in pain processing few in vivo studies on the thalamic neurochemical correlates of pain have been done. In the present experiments a combination of capillary zone electrophoresis with laser-induced fluorescence detection (CZE-LIF) and microdialysis in freely moving rats was used to measure extracellular arginine, glutamate and aspartate in the thalamus during the formalin test. Microdialysis probes were implanted in the left ventral posterolateral (VPL) nucleus of the thalamus in rats. Samples were collected every 30 s, derivatized with fluorescein isothyocyanate and injected into a CZE-LIF instrument. After nine baseline samples, a subcutaneous formalin (5%, 50 microl) injection in the right hind paw caused an increase of arginine, glutamate and aspartate that lasted for about 3 min. These increases were calcium and nerve impulse dependent. These results indicate that the release of arginine, glutamate and aspartate may mediate rapid pain neural transmission in the VPL nucleus of the thalamus.     

Synaptic arrangements in the ventral posterolateral nucleus of the squirrel

Because murine rodents have no complex synaptic arrangements in the ventral posterolateral nucleus (VPL), we sought to determine if the lack of complexity was a characteristic common to all rodents. We studied the synaptology of VPL in the fox squirrel, Sciurus niger, using electron microscopy. We found vesicle-containing dendrites and complex synaptic arrangements in the squirrel VPL. Therefore, the relative simplicity of the rat and mouse VPL is not a general feature of the rodent somatosensory thalamus.     

Projection from the external pallidum to the reticular thalamic nucleus in the squirrel monkey

Small injections of biocytin in the external segment of the pallidum (GPe) of the squirrel monkey (Saimiri sciureus) led to anterograde labeling of fibers in the thalamic reticular nucleus (NRT). These fibers reached NRT by coursing along the ventral tip of the internal capsule or by directly piercing the internal capsule more dorsally. They arborized profusely within the entire rostrocaudal extent of the nucleus. Within NRT, biocytin-labeled fibers were long, slightly varicosed, and emitted numerous short collaterals whose terminal portions consisted of clusters of large varicosities. Some of these varicosities were closely apposed to cell bodies and proximal dendrites of NRT neurons. Small injections of wheat germ-agglutinated horseradish peroxidase in the rostral pole of NRT led to retrograde cell labeling within the entire rostrocaudal extent of GPe. These retrogradely-labeled cells did not display immunoreactivity for choline acetyltransferase. Hence, beside the well-established projection from the internal pallidum to the thalamus, our findings support the existence of another pallidothalamic projection whereby GPe neurons could exert a powerful influence upon the thalamocortical neurons via a relay in NRT.     

Differences between somatosensory-evoked potentials recorded from the ventral posterolateral thalamic nucleus, primary somatosensory cortex and vertex in the rat

Somatosensory-evoked potential (SEP) components recorded over the primary somatosensory cortex (SI) and vertex in the rat within the 10-30 ms latency range were characterised with respect to the anatomy and function of the primary somatosensory pathway. To this aim, these components were compared to SEP components in the similar latency range recorded from the ventral posterolateral thalamic (VPL) nucleus, a nucleus known to be part of the subcortical structure of the primary somatosensory pathway and were described with respect to their stimulus-response characteristics and their response to the mu-opioid agonist fentanyl. The VPL positive (P)11-negative (N)18-P22 and SI P13-N18-P22 differed with respect to peak occurrence (P11 versus P13, respectively) and waveform morphology, but did not differ with respect to stimulus-response characteristics and their response to fentanyl. When compared to the vertex P15-N19-P26, the VPL P11-N18-P22 and SI P13-N18-P22 complex follow a relatively fast acquisition in stimulus intensity-response and were affected significantly less to increasing stimulus frequencies and to fentanyl. These results demonstrated that when compared to the VPL-SEP and SI-SEP, the Vx-SEP was modulated differently by the experimental conditions. It is suggested that this may be related to involvement of neural structures within different functional somatosensory pathways.     

Unit responses in the ventrobasal thalamus (VPL) of the cat to bradykinin injected into somatic and visceral arteries

Under light to moderate sodium pentobarbital anesthesia one half of the thalamic neurons displaying place and modality specific responses to low intensity mechanical stimulation of contralateral receptive fields also responded, by excitation or by inhibition, to bradykinin injections into somatic and visceral arteries. Partial or complete somatovisceral convergence was commonly seen in neurons with otherwise typical lemniscal properties. The response intensities varied considerably for different neurons; the responses to somatic bradykinin were always stronger than to visceral injections. The time course of the response was comparable to that seen in peripheral nerves, other central sites, and the behavioral reaction to bradykinin. Control experiments indicated the independence of the bradykinin responses from variations in blood pressure or general arousal effects. It is suggested that modulation of ventrobasal thalamic activity may be an important factor in central nociceptive processing.     

Ascending inhibition of nociceptive neurons in the nucleus ventralis posterolateralis following conditioning stimulation of the nucleus raphe magnus

Recordings were made from neurons in the nucleus ventralis posterolateralis (VPL) of urethane-chloralose-anesthetized cats, following both noxious mechanical stimulation of the integument and electrical stimulation of the greater splanchnic nerve (SPL). The effects of stimulating the nucleus raphe magnus (NRM) on responses obtained from these units were investigated. Units responding to noxious mechanical stimulation of the integument with SPL input were found in the posterior shell region of the VPL. Responses elicited from these units by electrical stimulation of the SPL were inhibited following conditioning stimulation in or near the NRM. Inhibition could still be demonstrated after bilateral section of the dorsolateral funiculi at the level of C₃−C₄. Responses of these units to electrical stimulation of the ventrolateral funiculus (VLF) of the cervical cord were also inhibited following conditioning stimulation in or near the NRM. These results suggest that inhibition of these units produced by conditioning NRM stimulation may be partially mediated by an ascending pathway, in addition to the well-known descending spinal pathways. Glutamate stimulation of the NRM inhibited responses of nociceptive VPL units to SPL stimulation, but responses of the same units to VLF stimulation were little affected by the glutamate stimulation of the NRM. Inhibition of responses of nociceptive VPL units to SPL stimulation may be due to anti-dromic excitation of brainstem neurons having efferent connection with the NRM.     

Axonal polyglucosan body in the ventral posterolateral nucleus of the human thalamus in relation to ageing

Summary Axonal polyglucosan bodies in myelinated axons in the ventral posterolateral nucleus of the human thalamus (VPL) are described. These axonal inclusions were distributed exclusively in the dorsolateral part of the caudal VPL, and their arrangement may be associated with fibres originating from the gracile nucleus. They were not observed in patients under age of 50, and appeared to increase in number and size with advancing age. It is suggested that axonal polyglucosan bodies are an ageing phenomenon of the secondary sensory fibers.     

Serotoninergic and noradrenergic projections to the ventral posterolateral nucleus of the monkey thalamus

In the present study, serotoninergic and noradrenergic varicosities were identified in the ventral posterolateral nucleus of the macaque monkey. Monoaminergic neurons projecting to the ventral posterolateral nucleus of the thalamus were identified by using retrograde labeling with horseradish peroxidase combined with immunocytochemical staining for serotonin or dopamine-beta-hydroxylase. The midbrain nucleus raphe dorsalis was the major site of origin for neurons providing a serotoninergic projection to the ventral posterolateral nucleus. A few retrogradely labeled serotonin-containing neurons were also observed in the central superior and the raphe pontis nuclei. Noradrenergic cells with projections to the thalamus were primarily located in the nucleus locus coeruleus with some projection neurons in the nucleus subcoeruleus, and the A5 catecholamine cell group of the pons.     

Somatosensory thalamus of a prosimian primate (Galago senegalensis). II. An HRP and Golgi study of the ventral posterolateral nucleus (VPL)

The topographic arrangement and cytoarchitecture of cells in the ventral posterolateral nucleus (VPL) of a prosimian primate (Galago senegalensis) were studied using horseradish peroxidase (HRP) and Golgi impregnation techniques. Following cortical implants of HRP, reactive neurons in VPL are organized into medially concave lamellae which extend through the dorsoventral and rostrocaudal dimensions of the nucleus. After implant in forelimb and hindlimb areas of motor-sensory cortex, labeled cells are confined to the medial (VPL_m) and lateral (VPL_l) portions of VPL, respectively. HRP-positive cells in the ventral part of each lamella are organized into clusters which correspond to the clusters of cells and “parcellated-bursts” of preterminal debris previously described in bushbaby VPL (Pearson and Haines, this volume). HRP-reactive cells in the ventral intermediate nucleus (Vim) are evenly distributed as contrasted to the tightly clustered groups of somata in the adjacent VPL. This evidence argues in favor of the presence of Vim in dorsal thalamus of this prosimian. Golgi impregnations reveal two main types of relay cells in Galago VPL. Type I cells have multiangular somata, straight distal dendrites, and primary dendritic branch points which are free of appendages. Type II cells have rounded somata, sinuous distal dendrites, and clusters of appendages located at primary branch points. Intermediate cells (i.e., cells with morphological features in between types I and II) are also present in VPL. Comparison of tufted Golgi impregnated cells with neurons labeled with HRP shows definite similarities in somata size and shape, and in the orientation of proximal dendrites. This evidence corroborates the relay nature of the tufted neurons in VPL. Relay cells in Galago VPL have morphological features which are similar to those of relay cells in lateral and medial geniculate nuclei of cat and primate. Type III cells have small round somata, radiate dendrites with elaborate appendages, and axons which appear to be intrinsic to VPL. Consequently, these cells are considered to be interneurons in the VPL of Galago. Glial-like neurons (type IV cells) were also observed. These have beaded dendritic processes similar to those which presumably represent presynaptic boutons in other species. Consequently, these cells are also assumed to function intrinsically within VPL.     

Electron microscopic evidence that cortical terminals make direct contact onto cells of the thalamic reticular nucleus in the monkey

Injections of WGA-HRP were made into somatosensory cortex to determine whether or not the cortex makes monosynaptic connections with neurons of the thalamic reticular nucleus. Two classes of synaptic profiles making asymmetric contacts onto small dendrites were labeled. The first class was small, and contained densely packed vesicles and few mitochondria. The second, larger class contained loosely packed vesicles, several mitochondria, and accounted for approximately one-third of labeled contacts.     

Projection from the deep cerebellar nuclei to the pedunculopontine nucleus in the squirrel monkey

Large injections of the anterograde tracer biocytin in the deep nuclei of the cerebellum of squirrel monkeys (Saimiri sciureus) led to a massive labeling of the superior cerebellar peduncle fibers which could be followed up to their major termination site in the thalamus. Along their course through the brainstem, biocytin-labeled fibers emitted fine collaterals that arborized profusely within the entire rostrocaudal extent of the pedunculopontine nucleus (PPN). These fibers were long, slightly varicose, and broke off into numerous shorter and thinner fibers whose terminal portions consisted of a few large varicosities that were often closely apposed to dendrites and cell bodies of PPN neurons. Some PPN cells that were contacted displayed immunoreactivity for choline acetyltransferase. Ultrastructural analysis revealed that synapses formed by cerebellar fibers in PPN were of the asymmetric type and occurred predominantly on dendrites of PPN neurons. Thus, beside the well established cerebellothalamic projection, our findings reveal the existence of a cerebellotegmental projection, whereby the cerebellum may influence the basal ganglia and/or the thalamus via a relay in PPN.     

Noxious stimuli excite neurons in nucleus submedius of the normal and arthritic rat

Anatomical studies have revealed the existence of an ascending pathway originating in the spinal cord and medullary dorsal horn, relaying in nucleus submedius (Sm) in medial thalamus and terminating in ventrolateral orbital cortex. It has been suggested that this pathway may be involved in the transmission of nociceptive information. In the present study extracellular recordings were obtained from neurons in Sm of anesthetized arthritic and normal rats. Mechanical and thermal stimuli were delivered to various regions of the body to determine the types of somatic stimuli which could activate Sm neurons. Over 40% of the 146 neurons studied responded to somatic stimuli. In the normal rats only high intensity mechanical and thermal stimuli were effective in inducing responses. In the arthritic rats lower intensity mechanical stimuli, joint movements and high intensity thermal stimuli were effective. Such stimuli produce nociceptive reactions in the freely moving arthritic rat. Almost all the responses were excitatory and generally lasted the entire duration of the 15-s stimuli employed. In some cases after-discharges were present. The receptive fields of the neurons were in almost all cases large and bilateral. These findings support the hypothesis that Sm may be involved in mediating the affective-motivational aspects of pain.     

Intratrigeminal and thalamic projections of nucleus caudalis in the squirrel monkey (Saimiri sciureus): a degeneration and autoradiographic study.

In order to test the hypothesis that thalamic efferents of trigeminal nucleus caudalis (NC) are the cranial analogue of the spinothalamic system, lesion and autoradiographic studies were carried out in the squirrel monkey, and the terminal projection fields in thalamus were noted. Results showed that NC, including lateral reticular formation (LRF), projects to contralateral VPM, the VPM-VPL border and medial VPL, and a region dorsal to ventroposterior nucleus (VP) proper which contains cells larger than those in VPM yet which stain as darkly as VPL neurons; this latter zone of termination may be homologous with VPL_o (Vim) in other species, which is that area receiving lemniscal and cerebellar afferents (Mehler, '71; Walsh and Ebner, '73; Boivie, '74). In addition, a small projection is noted in an area intercalated between dorsomedial MG, limitans nucleus and posterior VP which closely agrees with the medial division of Posterior nucleus (Po) described in rhesus and squirrel monkey (Burton and Jones, '76). No terminations were observed in the gustatory nucleus medial to VPM. Bilateral, terminal projection fields were observed in posterior mediodorsal nucleus (MD), and a paralaminar area (PL) which lies in the ventrolateral strip of MD and is particularly prominent in primates; other bilateral fields were noted in CL, particularly the more medial segment of the nucleus. A sparse projection was noted in contralateral CM. Ipsilateral, intratrigeminal connections between NC and main sensory nucleus (MSV) also were observed. We conclude that, in the squirrel monkey, NC efferents, probably including LRF, may be considered analagous to the spinothalamic system by virtue of terminations in older medial and newer ventroposterior thalamus. Terminations in posterior MD may be specific to Primates. Moreover, projections to an area just dorsal to VP proper in squirrel monkey may be included within the broader definition of a neo-spinothalamic area as reflected in spinothalamic tract projections to the ventrolateral complex in cat (Boivie, '71b; Jones and Burton, '74). The small NC projection to a part of Po is consistent with spinothalamic terminations to a “posterior” thalamic area in other primates (Mehler, '69), and with the suggestion that medial Po transmits pain information (Burton and Jones, '76).     

CB1 receptor mediated analgesia from the Nucleus Reticularis Gigantocellularis pars alpha is activated in an animal model of neuropathic pain

Cannabinoids are known to suppress responses to noxious stimulation in animals and man. Recent research has suggested a role for endogenous cannabinoids in the descending inhibition of dorsal horn cells via a supraspinal site of action. We have recently demonstrated [J. Physiol. 506(2) (1998) 459] that the nucleus reticularis gigantocellularis pars alpha (GiA) is a major source of such descending modulation, and importantly, that this system is activated in response to noxious stimulation. We have therefore investigated the role of CB1 receptor activation in mediating the antinociceptive effects of activation of GiA in models of acute and chronic pain. Microinjections (0.5 μl 60% DMSO) of either WIN 55,212-2 (5 μg, selective CB1 agonist), SR141716A (50 μg, competitive CB1 antagonist), both compounds together, or vehicle alone into GiA were performed prior to these tests in a randomised, blind manner. In control animals, WIN 55,212-2 markedly increased withdrawal latencies in the tail flick test and reduced responses to subcutaneous formalin. These effects were blocked by co-administration of SR141716A. These data suggest that activation of cannabinoid CB1 receptor subtypes in GiA leads to behavioural analgesia. In animals with partial sciatic nerve ligation, microinjection of drugs and injection of formalin were performed contralaterally to the site of ligation. Partial sciatic nerve ligation significantly reduced behavioural responses to contralaterally applied formalin. Microinjection of SR141716A to GiA reversed this inhibition of responses to formalin in animals with partial sciatic nerve ligation. These data provide evidence that endogenous CB1 receptor ligands are involved in GiA mediated antinociception, and that this system is important for the modulation of nociceptive transmission in an animal model of chronic neuropathic pain.     

Responses of neurons in the caudal intralaminar thalamic complex of the rat to stimulation of the uterus, vagina, cervix, colon and skin

This study examined responses of 35 neurons in the caudal intralaminar (IL) thalamic nuclei in 12 adult female virgin rats to mechanical stimulation of the skin (brush, pressure, pinch) and to 4 different visceral stimuli (noxious distension of the uterine horns and vaginal canal; gentle distension of the colon and probing the cervix). As in male rats and other species, many IL neurons () responded to frankly noxious somatic stimuli applied to several bodily regions. Some of these () also responded to one or more of the visceral stimuli (mainly the noxious ones), while responded only to a visceral stimulus. Thus, unlike neurons in lateral thalamus studied under identical conditions, IL neurons appear to be signalling information primarily when intense somatic and visceral stimuli are frankly above the noxious threshold.     

Inhibition of primate spinothalamic tract neurons by stimulation in ipsilateral or contralateral ventral posterior lateral (VPLc) thalamic nucleus

The effects of stimulation in the ventral posterior lateral (VPLc) thalamic nuclei on the activity of primate spinothalamic tract neurons were investigated. All 19 cells studied were strongly inhibited by conditioning trains of stimuli delivered to either ipsilateral or contralateral VPLc. Both background discharges and activity evoked by innocuous or noxious cutaneous stimulation were inhibited.     

The vestibular nuclei of the rat project to the lateral part of the thalamic parafascicular nucleus (centromedian nucleus in primates)

To clarify the vestibular projections to the centromedian-parafascicular nuclear complex, thePhaseolus vulgaris leucoagglutinin (PHA-L) and horseradish peroxidase conjugated to wheat germ agglutinin (WGA-HRP), tracing studies have been done in rats. The data demonstrated that the lateral parafasicular nucleus received vestibular afferents mainly from the ventral part of medial vestibular nucleus, and the superior and inferior vestibular nuclei, with an ipsilateral predominance. These findings suggest the vestibular influence to the motor loop of the basal ganglia thalamocortical projections.     

The functional role of the medio dorsal thalamic nucleus in olfaction

Olfaction is unique relative to other sensory modalities in terms of how its neuroanatomy is organized within the brain and its perceptual properties. Olfactory information processing occurs via connections made directly from primary processing areas (piriform cortex) to neocortical structures (orbitofrontal cortex) as well as indirectly via the medio-dorsal nucleus of the thalamus (MDNT). To date, little is known about the functional significance of the MDNT in olfactory information processing. The aim of this article is to review and discuss thalamic function in olfaction. We draw upon research in human neuroimaging, neuropsychology, as well as animal and neurophysiological studies on the thalamus and MDNT in general, before focusing our discussion on the effects of MDNT lesions specific to olfactory function. Finally, although these data are currently limited and sometimes conflicting, especially those based upon human pathology, the putative roles of the MDNT in olfactory information processing and notably its role in attention, are discussed.     

Types of synapses and degeneration in the thalamic nucleus ventralis oralis posterior after cerebellar lesions in the squirrel monkey

The thalamic nucleus ventralis oralis posterior (V.o.p) of Saimiri sciureus corresponds to the posterior basal part of the ventral lateral nucleus and is characterized by medium-sized nerve cells. Electron microscopic study revealed seven different types of synapses and the size of vesicles in each has been quantitatively determined. The synapse of type I LR (Large with Rounded vesicles) is considerably larger than the similar type IV MR (Medium-sized with Rounded vesicles) both contain round to ovoid vesicles and a large amount of mitochondria. Their contacts are asymmetric with presynaptic aggregations of synaptic vesicles. The type I LR synapses may also form button-like contacts (adhering junctions) without presynaptic accumulation of synaptic vesicles. The type II F (large with Flattened vesicles) symmetric synapses are formed by large boutons containing flattened vesicles and are partially encircled by astrocytic processes. The type III SR (Small with Rounded vesicles) bouton possesses small, nearly round till ovoid dense vesicles and forms a strongly asymmetric contact. In the type V SO (Small with Ovoid vesicles) bouton, the pleomorphic vesicles are larger than in type III and form asymmetric contacts with relatively small dendrites. Finally, two types of dendritic terminals were distinguished (VI and VII), which can be differentiated chiefly by the distribution of synaptic vesicles; VI DE (Dendritic terminal with Evenly distributed vesicles) and VII DC (Dendritic terminal with Clustered vesicles). Following hemicerebellectomy (4 experiments), only the type I LR and type IV MR synapses were found to be degenerated in the thalamic nucleus V.o.p. Similar degeneration was found in the ventral intermediate nucleus (V.im) which corresponds to the most rostral part of the VPL nucleus (VPLo). After three days survival, the forms of degeneration were largely neurofilamentous or pale, becoming mostly dark after four days. Degeneration of these same types of synapses appeared also in the nucleus ventralis oralis internus (V.o.i) and in the nucleus dorsalis intermedius (D.im), which lies above the ventral intermediate and ventrocaudal nuclei of the thalamus. These results are in good agreement with the findings in the light microscopic investigations if one considers the cyto- and myeloarchitectonic boundaries between the V.o.p and V.im.     

Cytoarchitectonic delineation of the ventral lateral thalamic region in the monkey

The cytoarchitecture of the ventral lateral region of the primate thalamus has been appraised in the frontal, parasagittal and horizontal planes. A morphologically distinct region, possessing a sparse and diffuse distribution of large and small neurons is identified. The region includes several nuclei previously separately named by Olszewski⁴⁵. These are nuclei VPLo, VLc, X, VLps, and some cellular extensions into the VLo nucleus. The whole zone is continuous, and it is shown that no clear separation exists between any of the previously identified sub-nuclei. Connectional grounds are given for suggesting that this region should be considered as a common cerebellar relay nucleus to motor cortex.Morphological criteria for distinguishing the cellsparse nucleus from adjacent nuclei are given. These cytological criteria provide a basis for the experimental analysis of cortical and subcortical connectivity of the ventral lateral thalamic region. Close attention was paid to the border between the VPLo nucleus and the VPLc nucleus. VPLc is separated from VPLo by a clear border, and no transitional zone can be detected in the parasagittal or horizontal planes. Previous ambiguities in the delineation of the VPLo-VPLc border probably stem from analysis in the frontal plane, in which the border is not clear.