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Evidence for reactive synaptogenesis in the ventrolateral thalamus and red nucleus of the rat: changes in high affinity glutamate uptake and numbers of corticofugal fiber terminals.

High affinity glutamate uptake into corticofugal fiber terminals was measured in the ventrolateral thalamus and red nucleus at varying time intervals after lesions were made by kainic acid in the contralateral interpositus nucleus of the cerebellum in rats. Under similar conditions the density of cortical fiber terminals was estimated using the Fink-Heimer impregnation technique. 1. Glutamate uptake steadily increased in the ventrolateral thalamus up to 60 days after lesions in the contralateral cerebellum. 2. Similar changes were noted in the red nucleus. 3. The changes were dependent on the integrity of corticofugal fibers to the thalamus and red nucleus. 4. No changes in uptake of gamma-aminobutyric acid were noted. 5. Saturation curves for glutamate uptake suggested a change in the maximal number of transport sites. 6. Fink-Heimer degeneration studies showed an increase in cortical terminals in the ipsilateral ventrolateral thalamus and in both rostral and caudal regions of the red nucleus following lesions in the contralateral interpositus nucleus. The data are consistent with an increase in the number of cortical fiber terminals in reaction to loss of cerebellar input to the ventrolateral thalamus and red nucleus. This study correlates anatomical and biochemical evidence for collateral sprouting in a model based on electrophysiologic data in the red nucleus and extends the model to include the thalamus.

Animals↗

Neuronal activity in the monkey motor thalamus during bicuculline-induced dystonia.

Recent data suggest that a decreased basal ganglia output may occur in dystonia, resulting in an increased thalamic drive to the mesial premotor cortex. In a previous work we found that injection of the GABAA antagonist bicuculline into the rostral motor thalamus induced contralateral dystonic postures, whereas myoclonic jerks were frequent after injection into the caudal motor thalamus. In the present study, we performed electrophysiological recordings in the rostral and caudal parts of the ventrolateral thalamus of two cynomolgus monkeys before and after bicuculline injections or saline injections. Discharge frequencies of thalamic neurons were increased after bicuculline injections vs. controls. Their discharge pattern was more bursty in the caudal part in which bursts of neuronal activity were correlated with myoclonic jerks. After bicuculline injection, neurons responded more frequently and less selectively to passive limb movements in both parts of the motor thalamus. Conversely, the response to microstimulation increased after bicuculline injection, particularly in the caudal part. Our data show that acute bicuculline-induced dystonia is associated with a reversible overactivity and disorganization of neuronal activity in the motor thalamus. Such a phenomenon might induce an overspreading of cortical activity leading to dystonia. We postulate that the distinct clinical syndromes observed after bicuculline injections into the rostral and caudal motor thalamus are due to differences both in the neuronal circuitry within each thalamic nucleus and in segregated cortical projections.

Action Potentials↗

A lacertilian dorsal retinorecipient thalamus: a re-investigation in the old-world lizard Podarcis hispanica.

The aim of this work is to delineate the retinorecipient cell groups of the dorsal thalamus of lizards and to study some of the differential connections in order to help to understand the evolution of the visual system in tetrapods. Tract-tracing and immunohistochemical techniques were applied to the retinorecipient dorsal thalamus of the lizard Podarcis hispanica. The retina of Podarcis projects to four areas of the dorsal thalamus: nucleus ovalis (Ov), intergeniculate leaflet (IGL), dorsal lateral geniculate nucleus (GLD) and dorsolateral anterior nucleus (DLA). Nucleus ovalis shows a clear cell plate/neuropile organization and projects to the ventral thalamus. Thus, it seems to belong to the ventral rather than to the dorsal thalamus. The IGL contains large cells reactive for GABA and/or NPY immunohistochemistry. It is interconnected with the supra/retrochiasmatic hypothalamus and projects to the opposite thalamus and to the ipsilateral tectum. The caudal DLA, which lacks both GABA- and NPY-like immunoreactive cells, is reached by a few thin retinal fibers, although distal dendrites of DLA cells enter the GLD, suggesting an important retinal input. The DLA projects to the medial and dorsal telencephalic cortices. The GLD is the main retinorecipient thalamic structure that projects to the telencephalon. It shows a crude laminar organization in which cell plate neurons project to the ipsilateral pallial thickening, but it does not receive a descending projection from the visual telencephalon and thus differs from the GLD of other amniotic vertebrates. In the context of present knowledge, these results suggest that an IGL homologue is present in all tetrapods studied, whereas Ov seems to be restricted to diapsid vertebrates. Moreover, our data suggest that a unimodal visual projection to the telencephalon (arising from the GLD) first appeared in reptiles by segregation from a limbic (multimodal) thalamo-telencephalic pathway.

Animals↗

The primate motor thalamus.

The functional parcellation of the motor thalamus of primates has suffered from serious historical and technical drawbacks, which have led to extreme confusion. This is a problem when thalamic stereotaxy is again being use clinically. The cause usually imputed is the historical conflict between two main schools, the Vogt and the 'Anglo-American' (Michigan), which used different nomenclatures. In fact, the reasons are more profound and serious. A combination of them led to: an archaic, rigid conception of the 'thalamic nucleus'; overexploitation of cytoarchitectonic technique, comparative anatomy and cortical connections; underexploitation of subcortical afferent territories; recent misuse of these territories; hesitations in the use of the VA-VL system; and opposition between ventral ('relay') and dorsal ('associative') 'nuclei'. Previous and current parcellations and nomenclatures for the lateral region finally appeared inappropriate. Before presenting a new parcellation and nomenclature for the lateral region, we explain why we did not adopt one of most common or of recently proposed nomenclatures, and were led to make our own. This is established according to rational and historically grounded rules. Precise definition of thalamic elements is provided. A thalamic 'region' is a gross topographic division corresponding to the former nuclei. A 'territory' is defined as the cerebral space filled by afferent endings from one source. When having a distinct topography in a region, a given territory makes a 'subregion'. For each of the studied 'motor' territories a review was made of its known cortical projections. The thalamic space where neurons project to a given cortical target constitutes a 'source space'. Topographical comparison of the sources spaces with territories reveals that there is often no coincidence between different (afferent or efferent) neuronal set spaces. It appears that source spaces are coincident in the pallidal and nigral territories but not in the cerebellar territory where two topographically distinct source spaces could be distinguished. A 'thalamic nucleus' is defined as the intersection of a thalamocortical source space with one territory. A rapid review of the general anatomy of the diencephalon is made. The ('dorsal') thalamus is divided into 'allo-' and 'isothalamus', the latter with 'bushy' and 'microneurons'. The lateral region is isothalamic. The 'motor thalamus' makes the anterior part of the lateral region. The present work aims to analyse the functional anatomy of the 'motor thalamus' by using precise topography and three-dimensional analyses of the subcortical territories receiving from the cerebellar nuclei (part II), the medial nucleus of the pallidum (part III) and the pars reticulata and mixta of the substantia nigra (part IV). Large injections were used to obtain the maximal extent of each territory. A major deficiency of previous studies was inadequate catography. Reliance on ventricular (CA-CP) landmarks observed by use of orthogonal teleradiography is mandatory. A study was made of intra- and interspecific variations and their effect on stereotactic and cartographic precision in macaques. All three subcortical motor afferent territories to the motor thalamus of macaques are examined in precise cartography with three dimensional reconstructions, rotations and 'reslicing'. The motor thalamus is made up of three topographically distinct and separate territories: cerebellar, pallidal territory and nigral. They cover the entire anterior part of the lateral region. There is no polar subdivision without lower afferents in front of the pallidal and nigral territories and thus no reason for isolating a nucleus lateralis polaris or a polar VA. The cerebellar territory is continuous and dense, in front of the somesthetic nucleus and everywhere separate from it. It has a complex three-dimensional shape, strongly convex anteriorly. Its caudal portion is dorsal to the somesthetic nucleus.(ABSTRACT

Animals↗

Nitric oxide synthase in the adult and developing thalamus: histochemical and immunohistochemical study in the rat.

The distribution of neuronal elements that express nitric oxide synthase (NOS), the synthetic enzyme of the free radical nitric oxide, was investigated in the adult and developing rat thalamus by means of NADPH-diaphorase (NADPH-d) histochemistry, which is a marker of NOS. Immunocytochemistry was also used to confirm the equivalence between the histochemical pattern of staining and the distribution of the expression of the neuronal NOS isoform. In the adult thalamus, NADPH-d-positive and NOS-immunoreactive perikarya were selectively concentrated along the midline (in the paraventricular, rhomboid, and central medial nuclei) and in the dorsal and ventral lateral geniculate nuclei. Isolated clusters of stained neurons were also observed in the lateral posterior nucleus, in the dorsal part of the medial geniculate nucleus, and in the ventromedial nucleus. Positive perikarya were either absent or very sparse in the other thalamic nuclei. Many thalamic domains were, however, characterized by distinct patterns of NADPH-d-positive fibers, preterminal and terminal-like elements. The highest density of stained neuropil was observed in the anteroventral and anteromedial nuclei, in several of the midline nuclei, in the anterior intralaminar nuclei, and in the lateral and medial geniculate nuclei. Although histochemical reactivity was observed in the thalamus at birth, the intensity and the pattern of distribution of staining observed in adulthood was not achieved until the end of the third postnatal week. The NADPH-d histochemical positivity followed discrete developmental schedules in various thalamic domains, and different areas reached a mature pattern at different ages. In addition, populations of transiently stained neuronal cell bodies were observed in the medial thalamus during the first two postnatal weeks. These results show discrete patterns of expression of NOS in the adult and developing thalamus and suggest that nitric oxide may be involved in selected physiological and developmental roles in different thalamic domains.

Aging↗

GABA(B) receptor gene expression in monkey thalamus.

Expression of gamma-amino butyric acid type B (GABA[B]) receptor gene transcripts was examined in the macaque monkey thalamus by in situ hybridization, using monkey-specific cRNA probes. GABA(B) transcript expression was widespread and of much higher density in the dorsal thalamus than in the reticular nucleus and other parts of the ventral thalamus and was highest in the epithalamus. In the dorsal thalamus, highest mRNA levels were found in the anteroventral nucleus and in the parafascicular nucleus. Sensory relay nuclei showed moderate GABA(B) mRNA levels. Neurons of all sizes were labeled, suggesting expression in relay cells and interneurons, and there was no labeling of neuroglial cells. Following 10-day periods of monocular deprivation, levels of GABA(B) mRNA were decreased in the deprived magno- and parvo-cellular laminae of the dorsal lateral geniculate nuclei, indicating activity-dependent regulation. High levels of GABA(B) receptors in the dorsal thalamus are likely to reflect the high density of synaptic inputs from the reticular nucleus while low expression in the reticular nucleus implies weak, GABA(B)-mediated intrareticular inhibition.

Animals↗

The cingulate bridge between allocortex, isocortex and thalamus.

The Fink-Heimer silver impregnation and the autoradiographic methods were used to study the fiber projections of the cingulate cortex in the squirrel monkey. It was found that this cortex provides inputs to the straitum, thalamus and several areas of isocortex. Evidence was found for a number of fiber projections (1) Fibers from the anterior limbic area were traced to the central part of the head of the caudate nucleus, putamen, septum, dorsomedial nucleus of the thalamus, anterior hypothalamus and lateral basal nucleus of the amygdala. (2) Projections from the cingulate area were traced to the lateral part of the head of the caudate nucleus, putamen, and to the centromedian, anterior, lateral dorsal, and lateral ventral thalamic nuclei and to medial nuclei of the base of the pons. (3) There were porjections from the retrosplenial area of the anterior, lateral dorsal, dorsomedial, and posterior thalamic nuclei and lateral nuclei of the pons. These results indicate that most of the cingulate gyrus is an intermediate structure between the thalamus and overlying cortex. The anterior limbic area forms a bridge between the thalamus and other areas of the cingulate gyrus and the frontal cortex. (4) the retrosplenial area and the posterior part of the cingulate area bridge the adjacent visual snesory association cortex and pelvic areas of the snesory motor cortex, respectively. These areas of the cingulate gyrus project directly to the striatum as well as to the thalamus, structurally providing limbic system input to subcortical motor structures.

Animals↗

Topographic organization of convergent projections to the thalamus from the inferior colliculus and spinal cord in the rat.

The purpose of this study was to identify thalamic areas receiving convergent sensory inputs from acoustic and spinal projection systems in the rat. The topographic distribution of afferents to the thalamus from the inferior colliculus and spinal cord was examined by using WGA-HRP as an anterograde axonal tracer. Following injections in the inferior colliculus, terminal labeling was present in ventral, medial, and dorsal divisions of the medial genicuate body (MGB) and in adjacent areas of the posterior thalamus, including the posterior limitans nucleus, the posterior intralaminar nucleus, the marginal zone, the peripeduncular region, the lateral or parvicellular part of the subparafascicular nucleus, and a region intercalated between the posterior limitans nucleus and the suprageniculate nucleus. In the caudal thalamus spinal projections remained in the reticular formation medial to the collicular terminal field. At intermediate levels of the MG, however, the spinal projection began to overlap the collicular field, terminating in the medial division of the MG and in the posterior intralaminar nucleus, the marginal zone, the lateral subparafascicular nucleus, and the area between the suprageniculate and posterior limitans nuclei. More rostrally, the convergent field expanded to include aspects of the dorsal MG division. The extent to which afferent projections to the thalamus from the inferior colliculus and spinal cord converge is thus graded in the caudorostral plane, with the greatest overlap occurring at the level of the rostral third of the MGB. These observations identify potential areas of acoustic and somesthetic integration and may account for observations of neuronal plasticity in the thalamus in response to the pairing of acoustic and somesthetic inputs.

Afferent Pathways↗

Expression of cholecystokinin and somatostatin genes in the human thalamus.

The cholecystokinin (CCK) gene is expressed in thalamocortical and thalamo-striatal neurons of the rat. In the cat, this peptide is found in some intralaminar and midline nuclei, whereas somatostatin (SRIF) is expressed in the reticular nucleus of the cat but not in rat. Since the putative neurotransmitters used by thalamic neurons are still incompletely known, especially in humans, we investigated the expression of the CCK and SRIF genes in the human thalamus by using hybridization histochemistry. CCK mRNA was found in many neurons, located in several nuclei of the dorsal thalamus. They were especially numerous and widespread in the nuclei associated with the internal thalamic lamina. They formed a continuum in the basal medial thalamus, from the central-medial nucleus, through the centre median/parafascicular complex to the limitans and suprageniculate nuclei. In addition, neurons with CCK mRNA were found medially and laterally to the mediodorsal nucleus, in the midline and intralaminar nuclei. Only rare neurons with CCK mRNA were found in other nuclei (e.g., in the ventral group of nuclei). SRIF mRNA was found in many neurons of the reticular nucleus, but not in the dorsal thalamus. Neurochemical features of the human thalamus, for the genes studied here, resemble those found in the cat. SRIF may play a role in modulating dorsal thalamic impulses, which may be conveyed through CCK innervation to the striatum and, partly, to the cortex.

Adult↗

Downregulation of complexin I and complexin II in the medial thalamus is blocked by N-acetylcysteine in experimental Wernicke's encephalopathy.

Metabolic dysfunction as a consequence of thiamine (vitamin B1) deficiency (TD), a model of Wernicke's encephalopathy, leads to elevation of extracellular glutamate concentration in vulnerable brain regions consistent with the development of excitotoxicity. Complexin I and complexin II are two genes labeling principally inhibitory and excitatory synapses, respectively. Because current evidence supports an important role for complexins in the modulation of neurotransmitter release, we examined the involvement of both proteins in the pathology of the medial thalamus and inferior colliculus in TD rats by immunoblotting. At the symptomatic stage, complexin I and complexin II levels in the medial thalamus were decreased by 63% and 45%, respectively, compared to control animals, but were unchanged in the inferior colliculus. These changes in thalamus were also observed using immunohistochemical methods, and seemed to be due to downregulation of both proteins because synaptophysin levels were unaffected in this brain region. In addition, cotreatment with the antioxidant N- acetylcysteine prevented both neuronal loss and downregulation of complexins. Our findings suggest dysregulation of excitatory and inhibitory neurotransmitter release in the medial thalamus, which is not present in the inferior colliculus. Furthermore, loss of complexin I and II in the thalamus may be mediated by processes that involve oxidative stress. Such changes in complexin levels may contribute to the pathophysiology of thalamic damage in TD, and offer a potential basis for the well-known differences in pathology between this structure and the inferior colliculus in this disorder.

Acetylcysteine↗

Interactions between inputs from adjacent digits in somatosensory thalamus and cortex of the raccoon.

Interactions between somatosensory afferents arriving from different points in the periphery play an important role in sensory discrimination and also provide the substrate for plasticity following peripheral injury. To examine the extent and time course of such interactions, extracellular recordings were made from neurons in the primary somatosensory cortex and the ventroposterior lateral thalamus of anesthetized raccoons. Interactions between adjacent digits were studied using the conditioning-test paradigm in which a test pulse was delivered to the digit containing the neuron's receptive field (the on-focus digit) at various intervals following conditioning stimulation of an adjacent, off-focus digit. Off-focus stimulation produced predominantly inhibition of the test response with a maximum effect at 20-40 ms in both cortex and thalamus. The mean inhibition was approximately twice as large in the thalamus as in the cortex. Recordings were made in other animals after unmyelinated C fibers had been destroyed in the on-focus digit by subcutaneous injection of capsaicin. This resulted in a doubling of the responses evoked by the test stimulus in both regions, but the spontaneous discharge rate was not changed. The amount of inhibition produced in the cortex was unchanged by capsaicin treatment, but was reduced in the thalamus compared to control animals. This indicates that capsaicin-sensitive peripheral afferents provide a tonic control over interdigit inhibition in the thalamus.

Action Potentials↗

Arterial vascularization of the human thalamus: extra-parenchymal arterial groups.

The problem of the arterial vascularization of the human thalamus has been debated at length. Anatomical references concerning the thalamic arterial groups are contradictory and complex, preventing any solid application in practice. It is, therefore, difficult to produce reliable anatomical radio-clinical correlation. In this work, 12 adult human cerebellums (24 hemispheres) were dissected after intra-vascular injection. With care for clarification and standardization, the extra-parenchymal thalamic arteries were classified in six groups: pre-mamillary artery, perforating thalamic arteries, thalamo-geniculate arteries, perforating branches of the postero-medial, postero-lateral and anterior choroidal arteries. Variations in the pre-mamillary artery were rare. The origin of the perforating thalamic artery was unilateral in two of three cases. The origin of the thalamo-geniculate arteries arose between the posterior cerebral artery (53%) and the posterior choroidal arteries (43%). The postero-median choroidal artery was most often single and usually gave the perforating branches for the medial aspect of the thalamus. The postero-lateral choroidal artery was frequently multiple and essentially gave the perforating branches for the superior aspect of the thalamus. The pulvinarian branches most often rose from the postero-lateral choroidal arteries (two thirds of cases) and more rarely from the postero-median choroidal arteries (one third of cases). The anterior choroidal artery is a source of thalamic vascularization by its cisternal branches running towards the lateral thalamus. It can also participate in the vascularization of the pulvinar by the plexiform branches crossing the temporal horn of the lateral ventricle. This study has allowed definition of the intra-parenchymatous arterial map of the thalamus. This mapping is essential for producing anatomical radio-clinical correlations which are pertinent for therapeutic decisions.

Aged↗

Multiregional 1H-MRSI of the hippocampus, thalamus, and basal ganglia in schizophrenia.

BACKGROUND: The hippocampus, thalamus and basal ganglia are among the brain regions of major interest in schizophrenia. AIMS: The purpose of this study was to corroborate previous findings of reduced N-acetylaspartate in the hippocampal and thalamic regions and to investigate possible metabolite changes in the putamen in schizophrenia. METHOD: MRSI study of the thalamus, basal ganglia, and hippocampus in 13 schizophrenic patients under stable medication and age-matched healthy controls. RESULTS: A decrease of the N-acetylaspartate signal was found in the hippocampal region and the thalamus but not in the putamen of patients compared to controls. No significant group differences in the signals from creatine and phosphocreatine, and choline-containing compounds were found in the hippocampal region and the putamen but the signal from choline-containing compounds was decreased in the thalamus of patients. CONCLUSION: Metabolic processes in the basal ganglia of schizophrenic patients seem to be opposite the hippocampal and thalamus findings.

Adult↗

"Pusher syndrome" following cortical lesions that spare the thalamus.

Stroke patients with "pusher syndrome" show severe misperception of their own upright body orientation although visual-vestibular processing is almost intact. This dissociation argues for a second graviceptive system in humans for the perception of body orientation. Recent studies revealed that the posterior thalamus is an important part of this system. The present investigation aimed to study the cortical representation of this system beyond the thalamus. We evaluated 45 acute patients with and without contraversive pushing following left-or right-sided cortical lesions sparing the thalamus. In both hemispheres, the simple lesion overlap associated with contraversive pushing typically centered on the insular cortex and parts of the postcentral gyrus. The comparison between pusher patients and controls who were matched with respect to age, lesion size, and the frequency of spatial neglect, aphasia and visual field defects revealed only very small regions that were specific for the pusher patients with cortical damage sparing the thalamus. Obviously, the cortical structures representing our control of upright body orientation are in close anatomical proximity to those areas that induce aphasia in the left hemisphere and spatial neglect in the right hemisphere when lesioned. We conclude that in addition to the subcortical area previously identified in the posterior thalamus, parts of the insula and postcentral gyrus appear to contribute at cortical level to the processing of the afferent signals mediating the graviceptive information about upright body orientation.

Aged↗

Microvascularization of thalamus and metathalamus in common tree shrew (Tupaia glis).

The microangioarchitecture of the thalamus and metathalamus in common tree shrew (Tupaia glis) was studied using vascular corrosion cast/stereomicroscope and SEM technique. The arterial supply of the thalamus and metathalamus was found to originate from perforating branches of the posterior communicating artery, the posterior cerebral artery, the middle cerebral artery, and the anterior choroidal artery. These perforating arteries gave rise to numerous bipinnate arterioles which in turn, with decreasing vessel diameters, branched into a non-fenestrated capillary bed. Venous blood from the superficial parts of the thalamus and metathalamus was collected into the thalamocollicular vein, whereas venous blood from internal aspects of the thalamus was conveyed to the internal cerebral vein. Some venous blood from the most rostral part of the thalamus flowed into tributaries of the middle cerebral vein before draining into the cavernous sinus. Further, the thalamic and metathalamic vascular arrangement was found to be of centripetal type. In addition, thalamic arterial anastomosis was rarely observed. Thus, obstruction of thalamic blood supply could easily lead to thalamic infraction.

Animals↗

Expression of GABA transporters, GAT-1 and GAT-3, in the cerebral cortex and thalamus of the rat during postnatal development.

The cellular and subcellular localization of two GABA transporters, GAT-1 and GAT-3, was investigated using immunocytochemical methods in the rat cerebral cortex and thalamus during postnatal development. The distribution of the transporters is compared with that of the neuronal marker GABA, and with that of vimentin and of glial fibrillary acidic protein, which identify immature and mature astrocytes, respectively. Our observations show that the two transporters are already expressed at birth in both brain areas with the same cellular localization as in adult rats, as GAT-1 is present in growth cones and terminals only in the cortex, whereas both transporters are expressed in astrocytes in the cortex and thalamus. The distribution of GAT-1 and GAT-3 undergoes postnatal changes reflecting in general the neurogenetic events of the neocortex and thalamus and, more specifically, the maturation of GABAergic innervation. The adult-like pattern of expression is achieved in the third postnatal week in the cortex and in the second postnatal week in the thalamus. The early expression of GAT-1 in GABAergic terminals confirms previous studies showing the existence of neuronal mechanisms of GABA uptake from the embryonic stages. As for the glial localization, the precocious existence of two astrocytic GABA transporters suggests that they operate through different functional mechanisms from birth, whereas their exclusively glial expression in the thalamus indicates that the astroglia plays a major role in the transport, recycling and metabolism of thalamic GABA.

Aging↗

Morphine induced alterations of gamma-aminobutyric acid and taurine contents and L-glutamate decarboxylase activity in rat spinal cord and thalamus: possible correlates with analgesic action of morphine.

Acute administration of morphine induced significant increases of gamma-amino-butyric acid (GABA) content and L-glutamate decarboxylase (GAD) activity at the dorsal parts of the dorsal horn and surroundings of the central canal in the rat spinal cord, in which GABA inhibitory interneurons may play significant roles. In the thalamus, morphine also induced significant increases of GABA content and GAD activity in the vicinity of the ventrolateral part of the ventral nucleus (VM), entopeduncular nucleus (EP), nucleus reuniens thalami (RE), nucleus parafascicularis thalami (PF) and interpeduncular nucleus (IP), respectively. The most significant increase of GABA was observed in the VM and PF, which are known to receive neuronal inputs from secondary neurons involved in the perception of pain. In spite of well-known involvement of periaqueductal gray matter (PVG) in the occurrence of morphine analgesia, GABA content in this area did not change following acute administration of morphine. The above mentioned increases of GABA in the spinal cord and thalamus were antagonized by the pretreatment with levallorphan, a narcotic antagonist, and were not observed when an analgesic dose of sodium salicylate or pentazocine was administered. On the other hand, acute administration of morphine failed to alter the microdistribution of taurine (2-aminoethanesulfonic acid) in the rat spinal cord and thalamus, in which significant increases of GABA content were observed. Contrary to the results obtained in acutely morphine-treated rats, animals rendered dependent by the implantation of a morphine pellet showed significant increases of taurine content in the spinal cord, whereas no change in GABA contents was detected in both spinal cord and thalamus. The present results suggest that morphine analgesia may involve mechanisms intensifying the inputs of GABA inhibitory neurons at the levels of the spinal cord and thalamus, where the primary and secondary neurons involved in the perception of pain are terminated respectively. Possible involvement of alterations in spinal taurine contents in the occurrence of morphine dependence are also suggested.

Aminobutyrates↗

Evidence for a GABAergic projection from the substantia nigra to the ventromedial thalamus and to the superior colliculus of the rat.

Unilateral intranigral infusion of kainic acid (1.5 microgram) produced neuronal loss in the lateral two-thirds of the nigra while sparing axons en passage. Fink-Heimer silver impregnation revealed dense terminal degeneration in the nigra itself (both in the compacta and in the reticulata) and in areas of non-dopaminergic nigral projection such as the ventromedial (VM) nucleus of the thalamus, the superior colliculus and the reticular formation; only spare terminal degeneration was found in areas of dopaminergic projection such as the caudate and septum. In order to clarify the nature of the transmitter of the nigrothalamic and nigrocollicular neurons, the activity of glutamic decarboxylase (GAD), the marker of cholinergic neurons, was measured in the VM and ventrobasal (VB) thalamus and in the nigra of each side, 7 days after unilateral intranigral injection of kainic acid. GAD activity was reduced significantly in the VM-thalamus (-33%), in the superior colliculus (-40%) and in the substantia nigra (-18%) but not in the VB-thalamus of the lesioned side. CAT remained unchanged in these areas. Similar results were obtained in the thalamus and in the superior colliculus after electrocoagulative lesions of the nigra. The results indicate the existence of a nigrothalamic and of a nigrocollicular GABAergic pathway. This projection might play an important role in motor coordination and gaze control.

Animals↗