Ventrobasal Thalamus Research Articles

Receptive field properties of trigeminothalamic neurons in the rostral trigeminal sensory nuclei of cats.

This study described topographic and receptive field representation in the region of the rostral trigeminal nuclei, and evaluated whether thalamic neurons from the principal sensory nucleus relay muscle afferent information to the thalamus. Extracellular single-unit activity was recorded from anesthetized cats. Units were tested for responses to natural stimuli (i.e., air bursts, brushing, light pressure, and pinch) applied to the face and oral cavity, electrical stimulation of the masseter nerve, and ramp-and-hold movements of the jaw. The receptive fields and physiological properties for 110 units were studied; we were able to verify the recording site for 96 of these units. Most of the units had discrete receptive fields in the oral cavity, skin, hair, and masseter muscle. Only 2 units received convergent inputs. Stimulation of the ipsilateral and contralateral ventroposteromedial nucleus of the thalamus was performed to identify antidromically activated units. The results showed that the dorsal principal sensory nucleus received its input primarily from the oral cavity. Most of the units (85%) that were activated by antidromic stimulation from the ipsilateral thalamus were located in this nucleus. In contrast, 82% of the units that projected to the contralateral thalamus were located in the ventral principal sensory nucleus. A complete somatotopic representation of the ipsilateral face and oral cavity was observed in the ventral principal sensory nucleus. Although 24 units had muscle receptive fields, none were activated by stimulation of the ipsilateral thalamus, and only 1 responded to stimulation of the contralateral thalamus. Most of the units that were not antidromically driven were recorded outside of the cytoarchitectural boundaries of the principal sensory nucleus. Retrograde labeling of the rostral trigeminal nuclei indicated that most of the neurons in the dorsal principal sensory nucleus projected to the ipsilateral thalamus, whereas those in the ventral principal sensory nucleus projected to the contralateral thalamus. Taken together, these observations do not support the presence of a substantial relay for muscle afferent input from the dorsal principal sensory nucleus to the ventrobasal thalamus in cats.

Vibrissal stimulation affects glucose utilization in the trigeminal/somatosensory system of normal rats and rats prenatally exposed to ethanol

The effect of gestational ethanol exposure on stimulus-induced sensory activity in the trigeminal/somatosensory system was determined. The mature offspring of mothers fed an ethanol-containing diet (Et) or pair-fed a nutritionally matched control diet (Ct) were examined. The C-row mystacial whiskers were stimulated. Glucose utilization in the principal sensory nucleus of the trigeminal nerve (PSN), ventrobasal thalamus, and somatosensory cortex was determined with [14C]2-deoxyglucose autoradiography. In Ct- and Et-treated rats, whisker stimulation increased glucose utilization in C-row barrel(oid)s in the left PSN, the right ventrobasal thalamus, and the right somatosensory cortex. The rate of glucose utilization in the C-row barrel(oid)s and in nonstimulated regions was lower in the Et-treated rats than in controls. In the cortices of Ct-treated rats, the activity in the C-row barrels on the right side was greater than in the right nonbarrel somatosensory cortex. Et-treated rats also exhibited an increase in glucose utilization, albeit smaller than that in the Ct-treated rats. In contrast, the glucose utilization in the left B- and C-row barrels of Ct-treated rats was decreased. No such decrease was evident in the left cortices of Et-treated rats. Thus, stroking whiskers stimulates the activity of sites in the trigeminal/somatosensory system. In cortex, the definition of these sites is emphasized by depressed activity, i.e., "surround" inhibition, in sites connected via callosal or corticocortical projections. Prenatal exposure to ethanol depresses the metabolic activity regardless of the physiological state; however, the "surround" inhibition of cortical activity is eliminated by prenatal exposure to ethanol through an exuberant projection.

Some aspects of the synaptic circuitry underlying inhibition in the ventrobasal thalamus.

We describe here, and review, the ultrastructural features and synaptic relationships of flat-vesicle containing, presumptively inhibitory presynaptic elements in the glomerular and extraglomerular neuropils of the thalamic ventrobasal (VB) nucleus in monkey, cat and rat. This account is based on EM study of normal material, LM and EM immunocytochemistry for GABA, anterograde tracing with HRP and EM of physiologically characterized interneurons intracellularly injected with HRP. It emerges clearly from this study that attempts to categorize flat-vesicle containing terminals in thalamic tissue as either F-boutons (axon terminals with flattened synaptic vesicles and Gray type II synaptic specializations) or P-boutons (dendritic appendages of interneurons with flattened vesicles) by examining only single sections are likely to produce unreliable results. In many cases it is only by studying serial sections that such profiles can be unambiguously identified. Within glomeruli the P-boutons participate in triplet (triadic) synapses which are thought to mediate rapid feed forward inhibition of projection cells, and serial synaptic arrays involving other P-boutons. Since P-boutons from more than one interneuron are present in individual VB glomeruli, P-bouton to P-bouton synapses may mediate disinhibition of interneurons. We show that dendritic shafts of interneurons make and receive synaptic contacts and that in the monkey, at least, reciprocal synaptic contacts between shafts or between a shaft and a P-bouton are not uncommon. Finally, we confirm that in the rat VB there are insignificant numbers of P-boutons or cells with the morphological and transmitter characteristics of interneurons and we suggest that comparative electrophysiological studies of inhibitory events in rat VB versus those in cat or monkey VB during transmission of somatosensory information might help to clarify the roles of thalamic intrinsic neurons.

Reduced Retrograde Labeling of Diencephalic-Projecting Neurons in the Gracile Nucleus of the Monkey Following Removal of Dorsal Column Input

As part of an anatomical investigation of neuronal responses to deafferentation of the dorsal column nuclei by transection of the dorsal spinal columns, the uptake and retrograde transport of HRP by thalamic projection cells in the dorsal column nuclei was studied. The ventrobasal thalamus of 13 macaque monkeys was injected bilaterally with HRP at periods ranging from 3 to 364 days following intended unilateral transection of fasciculus gracilis at a mid- to upper thoracic level. The density of labeled cells in the gracile nuclei ipsilateral to complete lesions of fasciculus gracilis was compared with the density of labeled cells in the contralateral gracile nuclei that were fully innervated or partially denervated by an incomplete lesion. Also, the density of labeled cells in the fully innervated cuneate nuclei was compared. In general, there was a reduction in density of labeled cells in the gracile nuclei ipsilateral to complete lesions. without a corresponding decrement in labeled cells in the cuneate nuclei on that side. This result confirms effects on spinal motoneurons and on thalamocortical projection cells in the lateral geniculate nucleus following deafferentation. However, attempts to define a time course for the reduction in transport by lemniscal projection cells revealed an effect that was dramatic in some animals, partial in others, and not demonstrable in the remainder, without a clear relationship to time after surgery. This result is related to a literature which describes a variety of morphological, biochemical, electrophysiological, and behavioral effects of deafferentation which appear to wax and wane with time after neuronal injury.

Glutamate in terminals of thalamocortical fibers in rat somatic sensory cortex

Thalamocortical terminals in layer IV of the somatic sensory cortex (SI) were identified by anterograde transport from ventrobasal thalamus. They were large, contained loosely packed round clear vesicles and abundant mitochondria, and made asymmetric contacts mainly with dendritic spines. Post-embedding immunocytochemistry revealed these terminals to be enriched in glutamate. Levels of glutamate in thalamocortical terminals, and in dendritic spines postsynaptic to them, were significantly higher than in nearby dendrites, astroglia, or in GABAergic terminals (identified by double immunostaining). These results support glutamate as neurotransmitter in thalamocortical fibers, and suggest that dendritic spines may take up glutamate released by these terminals.

Regulation of growth-associated protein 43 (GAP-43) messenger RNA associated with plastic change in the adult rat barrel receptor complex

Plastic change occurs in the adult rat barrel receptor complex following peripheral deafferentation by removal of facial vibrissae (vibrissectomy) and can be prevented by prior depletion of brain norepinephrine. Growth-associated protein (GAP-43, B50, F1, pp46), a marker for synaptic reorganization, increases in the barrel cortex of adult rats following both peripheral and central deafferentation. Here we followed changes in GAP-43 mRNA expression in the barrel receptor system following vibrissectomy. Adult rats had unilateral total vibrissectomy with sparing of the central (C3) vibrissa. By in situ hybridization, GAP-43 mRNA first increased at 24h (9%, P < 0.05) in the ipsilateral trigeminal complex. Levels remained elevated (up to 25% of the unlesioned side) over the next 6 days, decreased to 88% at 7 days and returned to control levels at 14 days. Contralateral barrel cortex levels of GAP-43 mRNA increased by 14% at 4–5 days remained elevated through 7 days and returned to control levels by 14 days. Increased GAP-43 mRNA levels 6 days after vibrissectomy were reproduced by complete transection of the infraorbital nerve and were blocked by depletion of brain norepinephrine. No change occurred in ventrobasal thalamus GAP-43 mRNA at any time. Dot blot and Northern blot hybridizations of GAP-43 mRNA after vibrissectomy showed a 43% increase in the ipsilateral trigeminal complex and a 16% increase in the contralateral barrel cortex at 3 days and an 84% increase in ipsilateral trigeminal and 50% increase in contralateral barrel cortex GAP-43 mRNA at 6 days, respectively. Thus, deafferentation-induced plasticity in the barrel pathway depends upon norepinephrine and is associated with increase in both GAP-43 mRNA and protein suggesting that this may involve a structural change.

Estrogen induces synaptic plasticity in adult primate neurons.

The number of axosomatic synapses, the length of the synaptic plates and the perimeter of the post synaptic neuronal perikarya were assessed on thin sections from the infundibular hypothalamic nucleus and from the ventrobasal thalamus of 3 adult ovariectomized African green monkeys that were treated with estradiol valerate and of 3 control animals that were injected with vehicle. Estradiol valerate treatment resulted in a 61% [corrected] decrease in the number of axosomatic synapses in the infundibular hypothalamic nucleus. The length of the synaptic plates and the perimeter of the postsynaptic cells were not affected by the hormonal treatment. The decrease in the number of axosomatic synaptic inputs in the infundibular hypothalamic nucleus was accompanied by a significant increase in the glial ensheathing of neuronal somas. No effect of the hormonal treatment was detected in the ventrobasal thalamus. The results indicate that estrogen may induce glial and synaptic plasticity in the hypothalamus of adult primates.

Demyelination, and remyelination by Schwann cells and oligodendrocytes after kainate-induced neuronal depletion in the central nervous system

Excitotoxins are thought to kill neurons while sparing afferent fibers and axons of passage. The validity of this classical conclusion has recently been questioned by the demonstration of axonal demyelination. In addition, axons are submitted to a profound alteration of their glial environment. This work was, therefore, undertaken to reassess axonoglial interactions over time after an excitotoxic lesion in the rat. Ultrastructural studies were carried out in the ventrobasal thalamus two days to 18 months after neuronal depletion by in situ injections of kainic acid. In some cases, lemniscal afferents were identified by using anterograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase from the dorsal column nuclei. Two and four days after kainate injection, numerous dying axons displaying typical signs of Wallerian degeneration were observed in a neuropile characterized by the loss of neuronal somata and dendrites, an increase in number of microglia/macrophages and the disappearance of astrocytes. Ten and 12 days after kainate injection, degenerating axons were no longer observed although myelin degeneration of otherwise unaltered axons was ongoing with an accumulation of myelin remnants in the neuropile. At 16 and 20 days, the demyelination process was apparently complete and axons of different diameters were sometimes packed together. One and two months after kainate injection, the axonal environment changed again: remyelination of large-caliber axons occurred at the same time as reactive astrocytes, oligodendrocytes and numerous Schwann cells appeared in the tissue. Schwann cell processes surrounded aggregates of axons of diverse calibers, ensheathed small ones and myelinated larger ones. Axons were also remyelinated by oligodendrocytes. Horseradish peroxidase-labeled lemniscal afferents could be myelinated by either of the two cell types. After three months, the neuropile exhibited an increase in number of hypertrophied astrocytes and the progressive loss of any other cellular or axonal element. At this stage, remaining Schwann cells were surrounded by a glia limitans formed by astrocytic processes. These data indicate that although excitotoxins are sparing the axons, they are having a profound and complex effect on the axonal environment. Demyelination occurs over the first weeks, accompanying the loss of astrocytes and oligodendrocytes. Axonal ensheathment and remyelination takes place in a second period, associated with the reappearance of oligodendrocytes and recruitment of numerous Schwann cells, while reactive astrocytes appear in the tissue at a slightly later time. Over the following months, astrocytes occupy a greater proportion of the neuron-depleted territory and other elements decrease in number. These successive stages in alteration of axonoglial interactions seem to evolve in parallel to the changes in density and terminal morphology that we described earlier for myelinated afferent fibers to the excitotoxic lesion.

Responses of neurons in the gracile nucleus of cats to innocuous and noxious stimuli: basic characterization and antidromic activation from the thalamus.

1. Responses to innocuous and noxious mechanical and thermal stimuli were recorded from 90 neurons in the gracile nucleus of anesthetized cats. Cells were tested by antidromic activation for projections to the contralateral ventrobasal thalamus. 2. Cells were characterized broadly by their responses to mechanical stimuli as 1) responding only to tapping (16%), 2) fast-adapting to low-intensity mechanical stimuli (33%), or 3) slowly adapting (51%; most with a fast-adapting component to their responses). All fast-adapting cells and those slowly adapting cells that were tested with noxious heat were further categorized on the basis of their patterns of firing and responses to stimuli. These plus the tap-responsive cells comprised a more restricted sample of 76 categorized cells. 3. Many (22) slowly adapting cells responded to noxious heat (69% of tested slowly adapting cells; 29% of all categorized cells), either on the first application (9 cells) or after sensitization (13 cells), indicating input originating in nociceptors. Nearly all of these (21) responded more to intense pressure than to innocuous pressure. The majority of slowly adapting cells not responsive to noxious heat (5 of 8) or not tested with it (8 of 12) also responded more to intense than to innocuous pressure, suggesting possible input originating in nociceptors. Most cells that responded to noxious heat also had both rapidly and slowly adapting responses with low thresholds. Many were recorded in the range of the cluster region of the gracile nucleus. 4. Cells antidromically activated from the thalamus projected to the rostral part of the ventral posterior lateral nucleus, regardless of their physiological category, and included many with nociceptive input. Latencies of antidromic activation were shorter at more caudal locations in the gracile nucleus, indicating higher conduction velocities to the thalamus. Responses of antidromically activated cells to low-intensity phasic stimuli tended to be greater than those of cells not antidromically activated. 5. Background activity of the neurons was low, most firing at less than one spike/s. Antidromically activated cells had higher background activity than cells not antidromically activated. 6. The results indicate a greater proportion and more widespread distribution of cells with nociceptive input in the cat gracile nucleus than has been previously recognized. Many of these projected to the ventrobasal thalamus, showing that information originating in nociceptors can reach the thalamus through a dorsal column-medial lemniscal pathway in cats.

Widely distributed GABA-mediated afferent inhibition processes within the ventrobasal thalamus of rat and their possible relevance to pathological pain states and somatotopic plasticity.

We have recently described extensive inhibitory interactions between inputs to the ventroposterolateral (VPL) (Roberts and Wells 1990, 1991) and ventroposteromedial (VPM) (Salt 1989) portions of the ventrobasal nucleus of the thalamus (VB). We wished to determine whether (i) the inhibition observed in the VPL was operating at the thalamic level, (ii) was dependent on GABA receptors, (iii) was demonstrable on neurons of the ventro-posteromedial nucleus of the thalamus (VPM) and (iv) was operant on test responses evoked by natural stimuli. Conditioning stimulation of sciatic nerve afferents caused inhibition of air jet evoked test responses of single VB neurons in urethane-anaesthetized rats. Both VPM and VPL neurons were subject to inhibition by conditioning stimulation of hindlimb afferents, indicating the wide-spread nature of the inhibitory process. This inhibition was reduced by the iontophoretic application of SR95531, a GABAA receptor antagonist. We conclude that there is a widely distributed inhibitory system operating in the somatic thalamus which involves both the medial and lateral portions of the nucleus and is, at least in part, mediated by GABAA receptors. The possible involvement of inhibitory processes and intrinsic membrane properties of thalamic neurones in the somatotopic plasticity of the sensory thalamus following deafferentation and in deafferentation pain is discussed.

A simplified approach to retrograde/anterograde axonal labeling using combined injections of horseradish peroxidase and ibotenic acid

Combined injections of ibotenic acid and horseradish peroxidase (HRP) were made into the region of the mouse ventrobasal thalamus that is related to the large mystacial vibrissae. Examination 4 and 5 days later of the corresponding area of the primary somatosensory cortex (i.e., barrel cortex), in thick and in thin sections, showed it to contain numerous corticothalamic projection cells the somata, dendrites and axons of which were densely labeled by the retrograde transport of HRP. Analysis of serial thin sections showed that thalamocortical axon terminals, which had degenerated in response to the injection of ibotenic acid, formed approximately 20% of the asymmetrical synapses in barrel cortex. The fine structure and distribution in cortex of degenerating thalamocortical axon terminals and of intrinsic HRP-labeled corticothalamic axon terminals were identical to those reported in previous studies in which the injection of HRP into the thalamus was combined with the making of electrolytic lesions. This indicates that injecting ibotenic acid is an effective replacement for electrolytic lesioning of the thalamus. The combined injection of ibotenic acid and HRP represents a new and efficient approach for studying reciprocal projection pathways.

Vibrissectomy induced changes in GAP-43 immunoreactivity in the adult rat barrel cortex.

Within the rat primary somatosensory cortex, neurons responding principally to movement of each individual mystacial vibrissa are grouped together in structures termed barrels. Previous studies have examined changes in the area of cortex showing increased 2-deoxyglucose uptake in response to vibrissal stimulation. These studies have shown that chronic removal of all but the central (C3) vibrissa in adult rats induces an enlarged representation of the remaining C3 barrel in the contralateral cortex. This increase is prevented by cortical norepinephrine depletion. The major question raised by such studies is whether such plasticity is due to structural rearrangement or unmasking of otherwise silent synapses. In this study, antibodies to GAP-43, a presynaptic protein whose synthesis is related to neuronal development and regeneration, were used to investigate this issue. In adult rat brain, tangential sections through layer IV of the barrel receptor field normally show moderate levels of GAP-43 immunoreactivity (GAP-IR) in the inter-barrel septa and low levels within the barrels themselves. The present study examined changes in the pattern of GAP-IR from 1 to 8 weeks after vibrissectomy with sparing of C3 as an index of possible physical reorganization of cortical circuits. Quantitative analysis of the cortices of animals with unilateral vibrissectomy with sparing of C3 showed that the area of low GAP-IR within the barrels surrounding C3 was decreased at 1 week (8.4% shrinkage; P less than 0.01) and 8 weeks (12.0% shrinkage; P less than 0.015), relative to the cortex ipsilateral to the surgery. Both bilateral vibrissectomy with sparing of C3 and ibotenic acid lesions of the ventrobasal thalamus produced similar results. Some evidence was also seen that the area of low GAP-IR in the C3 barrel shrank to a similar degree after such manipulations. Cortical norepinephrine depletion had no apparent effect on vibrissectomy-induced GAP-IR changes. These results suggest that removal of vibrissal input to the adult rat barrel cortex produces transynaptic induction of axonal sprouting within the barrel cortex.

Facilitatory and Inhibitory Processes in the Thalamic Ventrobasal Nucleus of the Rat.

Experiments were carried out on anesthetized rats to clarify the actions of the corticothalamic input on the thalamic ventrobasal neuron (VB). The field potentials and the unit activities were evoked in the VB by the electrical stimulation of the contralateral (cSCx) and ipsilateral somatosensory cortex (SCx), the thalamic radiation (TR), and the medial lemniscus (ML). The corticothalamic axons could be activated from cSCx via the ipsilateral SCx, with the result of a clear excitation followed by the inhibition of VB neurons. These VB responses were also evoked from SCx, TR, or even ML with other responses. Paired stimulation of these sites revealed that the corticothalamic input exerted facilitation on the succeeding corticothalamic input for 690 +/- 74.2 ms (n = 5). It was confirmed that these corticothalamic actions were abolished by the lesion of SCx. In contrast to the corticothalamic-induced VB responses, the VB responses to ML input received powerful inhibitory effects from ML or SCx for 1,150 +/- 35.4 ms (n = 5). It is concluded that the corticothalamic input can excite the VB neuron in a mechanism that differs from that of ML input.

The medullary relay from neck receptors to somatosensory thalamus in the rat: a neuroanatomical study.

Experiments were performed on rats to determine the location of thalamic projecting neurones in the medulla which receive direct contacts from neck primary afferents. The medullary terminations of primary afferents from the cervical region were identified by silver staining their degenerating terminals, diffusely filling their axons with horseradish peroxidase (HRP), or reacting for transganglionically transported HRP applied to muscle or cutaneous nerves. Neurones projecting to the ventrobasal thalamus were identified in the same experimental animals by using retrograde transport of HRP or Fluoro-Gold. En passant swellings or terminals of neck primary afferents were found in the vicinity of neurones projecting to the thalamus in the dorsolateral part of the rostral cuneate nucleus, the ventral aspect of the external cuneate nucleus, and the border zone between the two. Terminals of neck afferents and retrogradely labelled cells also coincided in nucleus x. Putative synaptic contacts were found in the region between the dorsolateral part of the rostral cuneate nucleus and ventromedial external cuneate nucleus. Cutaneous afferents from the neck were associated with thalamic projecting cells located along the dorsolateral border of the rostral cuneate nucleus, and afferents from neck muscles were associated with thalamic projecting cells in the caudal third of the external cuneate nucleus and in nucleus x.

Efferent neurons and suspected interneurons in second somatosensory cortex of the awake rabbit: receptive fields and axonal properties

1. Receptive-field properties of antidromically identified efferent neurons within the representation of vibrissae and sinus hairs above the mouth were examined in secondary somatosensory cortex (S-2) of fully awake adult rabbits. Efferent neurons studied included callosal neurons (CC neurons, n = 88), ipsilateral corticocortical neurons (C-IC neurons, n = 51) that project to primary somatosensory cortex (S-1), and corticofugal neurons of layer 5 (CF-5 neurons, n = 63) and layer 6 (CF-6 neurons, n = 42) that project to and/or beyond the thalamus. Appropriate collision tests demonstrated that substantial numbers of corticocortical efferent neurons (21 of 113 tested) project an axon to both the corpus callosum and to ipsilateral S-1. 2. Suspected interneurons (SINs, n = 62) were also studied. These neurons were not activated antidromically from any stimulus site but did respond synaptically to electrical stimulation of the ventrobasal (VB) thalamus with a burst of three or more spikes at frequencies of 600 to greater than 900 Hz. Most of these neurons also responded synaptically to stimulation of S-1 and the corpus callosum. The action potentials of these neurons were much shorter (mean, 0.49 ms) than those of efferent neurons (mean, 1.01 ms). 3. CF-5 neurons differed from CC, C-IC, and CF-6 neurons in their spontaneous firing rates, axonal properties, and receptive-field properties. Whereas CF-5 neurons had a mean spontaneous firing rate of 5.7 spikes/s, CC, C-IC, and CF-6 neurons all had mean values of less than 1/s. Axonal conduction velocities of CF-5 neurons were much higher (mean, 11.90 m/s) than either CC (mean, 2.63 m/s), C-IC (mean, 0.86 m/s), or CF-6 (mean, 1.73 m/s) neurons. A decrease in antidromic latency (the "supernormal" period), which was dependent on prior impulse activity, was seen in most CC, C-IC, and CF-6 neurons but was minimal or absent in CF-5 neurons of comparable conduction velocity. Although all CF-5 neurons responded to peripheral sensory stimulation, many CC (52%), C-IC (49%), and CF-6 (55%) neurons did not. CC and CF-6 neurons that did not respond to sensory stimulation had significantly lower axonal conduction velocities and spontaneous firing rates than those that responded to such stimulation. Whereas no CC, C-IC, or CF-6 neuron responded synaptically to callosal stimulation, 43% of CF-5 neurons (and 78% of SINs) did so respond. Similar differences in synaptic responsivity to stimulation of S-1 were seen in these populations.(ABSTRACT TRUNCATED AT 400 WORDS)

Single neurone studies of opioid tolerance and dependence at the ventrobasal thalamic level in an experimental model of clinical pain, the arthritic rat

The aim of this electrophysiological study was to investigate the effects of an acute injection of morphine (1 mg/kg i.v.) or the opioid antagonist naloxone (0.6-2 mg/kg i.v.) on thalamic ventrobasal (VB) neuronal activities recorded in arthritic rats rendered tolerant/dependent by pretreatment with relatively low doses of morphine. Recordings were performed in animals immobilized by i.v. injections of gallamine triethiodide (Flaxedil) and artificially ventilated under a moderate gaseous anesthesia (mixture of one-third O2, two-thirds N2O, 0.5-0.6% halothane). This level of anesthesia, as checked by the electrocorticogram, was stable and appeared sufficiently deep, since no sign of suffering or stress could be detected. The efficacy of morphine on VB neuronal responses induced by mild stimulation of the joints was greatly reduced in morphine-pretreated arthritic rats, compared to naive animals (mean neuronal inhibition of 35 vs 85%, respectively). This indicates that the tolerance phenomena observed in behavioral studies are reflected at the VB level, on neurons involved in pain processes. In addition, naloxone (0.6, 1 and 2 mg/kg i.v.) induced a dramatic increase in the evoked (52, 88 and 93%) and spontaneous (64, 211 and 292%) VB neuronal activities recorded in morphine-pretreated arthritic rats, while these activities were not significantly altered in naive arthritic rats. The time-courses of the modifications induced by naloxone in morphine-pretreated arthritic animals were similar to those of the naloxone-precipitated morphine withdrawal observed in freely moving rats. These findings may represent the neuronal correlate at the VB level of the withdrawal response and/or the hyperalgesia induced in tolerant arthritic rats by high doses of naloxone.

Neural Processing of Craniovascular Pain: A Synthesis of the Central Structures Involved in Migraine

In order to determine the anatomical distribution of cells concerned with relaying craniovascular nociception, local cerebral glucose utilization was determined by the 2-deoxyglucose method in tissue autoradiographs of the alpha-chloralose anesthetized cat. The superior sagittal sinus was carefully lifted from the brain by sectioning the dura laterally and the falx inferiorly and suspending the sinus across two platinum hook electrodes for stimulation. The sinus was stimulated electrically and its effect on caudal brainstem, upper cervical spinal cord and diencephalic metabolic activity determined. Stimulation of the sinus caused increased metabolic activity in the trigeminal nucleus caudalis, in the cervical dorsal horn and in a discrete area in the dorsolateral spinal cord at the second cervical segment. Metabolic activity was also increased in the ventrobasal thalamus, specifically in the ventroposteromedial (188%) nuclear group, in the medial nucleus of the posterior complex (70%) and the intralaminar complex (49%). There was no change in the surrounding thalamus, lateral geniculate nucleus or overlying cerebral cortex. These increases in 2-deoxyglucose utilisation were blocked by bilateral trigeminal ganglion ablation. The dorsolateral area activated in the spinal cord corresponds to a hitherto unrecognised group of cells in or near the lateral cervical nucleus that may form an important relay for craniovascular nociception. Further electrophysiological studies with glass coated tungsten microelectrodes have characterised the cells in these regions of the thalamus to be responsible for relaying nociceptive information. An understanding of the connections and properties of the neurons that subserve craniovascular pain is an essential prerequisite to understanding the complex pathophysiology of migraine.

Electrophysiological evidence that morphine can exert an antinociceptive effect in a neuropathic state: a study in the ventrobasal thalamus of rats after moderate ligation of one sciatic nerve

This study was performed in rats with a mononeuropathy induced by loose ligatures around the common sciatic nerve 2 weeks before the recording session, and exhibiting clear alterations of several pain-related behaviours. Morphine injected intravenously (0.6 and 1 mg/kg) strongly depressed the ventrobasal thalamic neuronal responses to pinch applied to the lesioned or the non-lesioned hindpaw. The effect, comparable on the both sides, was dose-related and reversed by naloxone (0.1 mg/kg i.v.).

TRH analogue antagonizes anaesthetic induced depression of information transfer through the ventrobasal thalamus of the rat

Previous studies have indicated an anti-narcotic action of TRH and its analogues. A major site of anaesthetic action is in the ventrobasal thalamus (VBT). The present experiments were performed to determine whether there was antagonism between anaesthetics and a TRH analogue on VBT transmission. It was found that the TRH analogue CG3703 reversed the depressant actions of the anaesthetics urethane, sodium pentobarbitone and sodium brietal on ventrobasal transmission. These actions were also observed at the cortical level but cuneate transmission was unaffected. These results are discussed in the context of modulation of information flow through VBT. In particular it is suggested that TRHergic input from the thalamic reticular nucleus may be an important regulator of VBT transmission.

Thyroid hormone modulates the development of cholinergic terminal fields in the rat forebrain: relation to nerve growth factor receptor

Hyperthyroidism, induced in rat pups by the daily intraperitoneal administration of 1 μg/g body weight triiodothyronine, facilitated the development of ChAT fiber plexuses in brain regions innervated by basal forebrain cholinergic neurons, leading to an earlier and increased expression of cholinergic markers in those fibers in the cortex, hippocampus and amygdala. A similar enhancement was seen in the caudate-putamen complex. This histochemical profile was correlated with an accelerated appearance of ChAT-positive telencephalic puncta, as well as with a larger total number of cholinergic terminals expressed, which persisted throughout the eighth postnatal week, the longest time examined in the present study. Hypothyroidism was produced in rat pups by adding 0.5% propylthiouracil to the dams' diet beginning the day after birth. This dietary manipulation resulted in the diminished expression of ChAT in forebrain fibers and terminals. Hypothyroid treatment also reduced the quantity of ChAT puncta present during postnatal weeks 2 and 3, and, from week 4 and continuing through week 6, the number of ChAT-positive terminals in the telencephalic regions examined was actually less than the amount extant during the former developmental epoch. Immunostaining for nerve growth factor receptor (NGF-R), which is associated almost exclusively with ChAT-positive somata and fibers in the basal forebrain, demonstrated a different time course of postnatal development. Forebrain fibers and terminals demonstrating NGF-R were maximally visualized 1 week postnatally, a time at which these same neuronal elements evinced minimal ChAT-like immunopositivity. Thereafter and correlated with increased immunoreactivity for ChAT, fine details of NGF-R stained fibers were observed less frequently. Although propylthiouracil administration decreased NGF-R immunodensity, no alteration in the development of that receptor was observed as a function of triiodothyronine treatment. Cholinergic terminals in the ventrobasal thalamus, which derive from ChAT-positive neurons in the pedunculopontine and laterodorsal tegmental nucleus, were unaffected by either hyperthyroid or hypothyroid conditions. These cells also do not demonstrate NGF-R. We conclude from these experiments (1) that cholinergic fiber plexuses eventually exhibiting ChAT positivity in the telencephalon demonstrate NGF-R prior to the cholinergic synthetic enzyme, (2) that susceptibility to thyroid hormone manipulations may involve sensitivity to NGF, at least in some forebrain cholinergic systems and (3) that the effects of thyroid hormone imbalances on brain cholinergic neurons are regionally selective.