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Retinal projections to the midline and intralaminar thalamic nuclei in the common marmoset (Callithrix jacchus).

In this study, we report the identification of a hitherto not reported direct retinal projection to midline and intralaminar thalamic nuclei in the marmoset brain. After unilateral intravitreal injections of cholera toxin subunit B (CTb), anterogradely transported CTb-immunoreactive fibers and presumptive terminals were seen in the following thalamic midline nuclei: paraventricular, rhomboid, interanteromedial, and reuniens, and thalamic intralaminar nuclei: central medial, central lateral, central dorsal, and parafascicular. Studies employing sensitive tracers in other primate species are needed in order to verify the possible universality of these projections. Some of the possible functional correlates of the present data are briefly discussed. The present results may contribute to the elucidation of the anatomical substrate of the functionally demonstrated involvement of this midline/intralaminar thalamic nuclear complex in several domains that include arousal and awareness, besides specific cognitive, sensory, and motor functions.

Animals↗

Loss of thalamic intralaminar nuclei in progressive supranuclear palsy and Parkinson's disease: clinical and therapeutic implications.

Whilst many reports mention neurofibrillary tangle pathology in the thalamus in progressive supranuclear palsy, there has been little detailed regional analysis of the distribution and density of thalamic pathology in this disease or in other parkinsonian syndromes. The caudal intralaminar thalamic nuclei are the major thalamic regulators of the caudate nucleus and putamen, areas known to be dysfunctional in progressive supranuclear palsy and Parkinson's disease. We investigated whether these thalamic nuclei degenerate in patients with these disorders compared with age-matched, neurologically normal controls. Neurofibrillary tangle and Lewy body pathology was assessed and unbiased optical disector methods were used to quantify total neuronal number. Despite different thalamic pathology, there was a dramatic reduction in the total neuronal number in the caudal intralaminar nuclei in both progressive supranuclear palsy and Parkinson's disease (40-55% loss). In contrast, there was no loss of volume or total neuronal number in the limbic thalamic nuclei in either disease group, indicating selective degeneration of the caudal intralaminar nuclei. In Parkinson's disease, Lewy bodies were found in these regions, while in progressive supranuclear palsy abundant intracellular neurofibrillary tangles and glial tangles concentrated in the caudal intralaminar nuclei. However, tangle formation accounted for only a small proportion of cell loss (</=10%) in the thalamus in progressive supranuclear palsy. These findings have several implications. The caudal intralaminar thalamus appears to be one of three basal ganglia sites commonly affected in both progressive supranuclear palsy and Parkinson's disease. These sites are the dopaminergic substantia nigra, the cholinergic pedunculopontine tegmental nucleus and, from our results, the glutamatergic caudal intralaminar thalamus. In both diseases these sites contain characteristic but different pathologies, indicating disease-specific mechanisms of neurodegeneration. Interestingly, the proportion of remaining neurons affected by these pathologies is low. This may indicate additional (possibly common) cellular mechanisms responsible for the degeneration in these regions. Both the dopaminergic nigra and the glutamatergic caudal intralaminar thalamus are the major regulators of basal ganglia function via the caudate nucleus and putamen. The pedunculopontine tegmental nucleus has major projections to both of these regulators. These findings indicate that dysregulation of two neurotransmitter systems within the basal ganglia may underlie common parkinsonian symptoms in these disorders. For patients with Parkinson's disease, this loss of glutamate regulation may help explain some problems with dopamine replacement therapies, particularly over time. For patients with progressive supranuclear palsy, more widespread degeneration of basal ganglia structures would contribute to poor treatment outcomes.

Aged↗

The specificity of the 'nonspecific' midline and intralaminar thalamic nuclei.

The midline and intralaminar thalamic nuclei have long been considered to be a 'nonspecific' nuclear complex that relays the activity of the brain-stem reticular formation to widespread cerebral-cortical areas. Over the past decade, it has become clear that individual midline and intralaminar nuclei each receive specific sets of afferents and project to specific parts of the cerebral cortex and striatum. Moreover, the targets of the thalamocortical and thalamostriatal projections of a given nucleus are interconnected through corticostriatal projections. Therefore, the midline and intralaminar nuclei might have a dual role in corticosubcortical interactions in the forebrain. Through distinct sets of inputs to individual midline or intralaminar thalamic nuclei, these nuclei are in a position to interact selectively with particular, functionally segregated basal-ganglia-thalamocortical circuits. By way of nonselective inputs, in particular from cholinergic brain-stem nuclei, the midline and intralaminar nuclei might act in concert to modify the level of activity of the entire basal-ganglia-thalamocortical system.

Animals↗

GABA in the intralaminar thalamic nuclei modulates dopamine release from the two dopaminergic nigro-striatal pathways in the cat.

Halothane-anaesthetized cats implanted with several push-pull cannulae were used to study the effects of the unilateral application of GABA (10(-5) M, 30 min) into thalamic intralaminar nuclei on the in vivo release of (3H)-dopamine [3H)-DA) newly synthesized from (3H)-tyrosine in both caudate nuclei (CN) and substantiae nigrae (SN). GABA applied into the left centralis lateralis nucleus (CL) elicited symmetric changes in the two CN, (3H)-DA release being initially reduced and thereafter markedly increased. On the contrary, an asymmetric pattern of responses was observed in the two CN during and after GABA application into the left centrum medianum parafascicular complex (CM/PF) since (3H)-DA release was decreased ipsilaterally and enhanced contralaterally. Changes in (3H)-DA release intervening in the two SN appeared to be triggered by processes independant from those operating in the CN. Hence, an immediate increase in (3H)-DA release with a time course distinct from that observed in other structures occurred in the contralateral SN after the application of GABA either into the left CL or the left CM/Pf. Furthermore in both cases, a biphasic response (decrease followed by an increase) similar to that intervening in the CN following GABA application into the CL was seen in the ipsilateral SN. Autoradiographic studies performed with (14C)-GABA (10(-5) M) revealed that the amino-acid did not spread out from the site of application. During and after GABA application (10(-5) M, 30 min) into the CL or the CM/Pf neuronal firing was markedly enhanced not only locally but also into respective contralateral homologous structures. These results further confirm the important and specific roles of distinct thalamic nuclei in the bilateral regulation of DA release from dendrites and nerve terminals of the nigro-striatal dopaminergic neurons.

Animals↗

Brainstem projections to midline and intralaminar thalamic nuclei of the rat.

The projections from the brainstem to the midline and intralaminar thalamic nuclei were examined in the rat. Stereotaxic injections of the retrograde tracer cholera toxin beta -subunit (CTb) were made in each of the intralaminar nuclei of the dorsal thalamus: the lateral parafascicular, medial parafascicular, central lateral, paracentral, oval paracentral, and central medial nuclei; in the midline thalamic nuclei-the paraventricular, intermediodorsal, mediodorsal, paratenial, rhomboid, reuniens, and submedius nuclei; and, in the anteroventral, parvicellular part of the ventral posterior, and caudal ventral medial nuclei. The retrograde cell body labeling pattern within the brainstem nuclei was then analyzed. Nearly every thalamic site received a projection from the deep mesencephalic reticular, pedunculopontine tegmental, dorsal raphe, median raphe, laterodorsal tegmental, and locus coeruleus nuclei. Most intralaminar thalamic sites were also innervated by unique combinations of medullary and pontine reticular formation nuclei such as the subnucleus reticularis dorsalis, gigantocellular, dorsal paragigantocellular, lateral, parvicellular, caudal pontine, ventral pontine, and oral pontine reticular nuclei; the dorsomedial tegmental, subpeduncular tegmental, and ventral tegmental areas; and, the central tegmental field. In addition, most intralaminar injections resulted in retrograde cell body labeling in the substantia nigra, nucleus Darkschewitsch, interstitial nucleus of Cajal, and cuneiform nucleus. Details concerning the pathways from the spinal trigeminal, nucleus tractus solitarius, raphe magnus, raphe pallidus, and the rostral and caudal linear raphe nuclei to subsets of midline and intralaminar thalamic sites are discussed in the text. The discussion focuses on brainstem-thalamic pathways that are likely involved in arousal, somatosensory, and visceral functions.

Animals↗

Cortical topography of thalamic intralaminar nuclei.

The cortical projection of the thalamic intralaminar nuclei (ILN) has been studied by injecting little amounts of horseradish peroxidase (HRP) on the cerebral cortex of the rat. All of the cortical areas (except area 17) receive ipsilateral projections from at least one nucleus of the ILN. The nucleus centralis lateralis had the largest number of labeled neurons, principally after injections in frontal, temporal and occipital cortical areas. The nucleus paracentralis presented only moderate numbers of HRP positive neurons from the frontal cortex, and very few from parietal and temporal areas. The nucleus parafascicularis showed labeled somata after frontal injections as well as parietal and temporal areas. In comparison to the other ILN, the amount of labeled neurons in this nucleus is relatively small. The nucleus centralis medialis presented the least number of labeled neurons regardless of injected area. Its cortical efferents remain restricted to small areas of the dorsal aspects of frontal, anterior cingular and temporal cortices. Each of the ILN contains neurons which connect with more than one cortical zone, according to a characteristic topographic distribution.

Afferent Pathways↗

Restricted cortical termination fields of the midline and intralaminar thalamic nuclei in the rat.

The projections from the midline and intralaminar thalamic nuclei to the cerebral cortex were studied in the rat by means of anterograde tracing with Phaseolus vulgaris-leucoagglutinin. The midline and intralaminar nuclear complex taken as a whole projects to widespread, predominantly frontal, cortical areas. Each of the constituent thalamic nuclei has a restricted cortical projection field that overlaps only slightly with the projection fields of adjacent midline and intralaminar nuclei. The projections of the intralaminar nuclei cover a larger cortical area than those of the midline nuclei. The laminar distributions of fibres from individual midline and intralaminar thalamic nuclei are different and include both deep and superficial cortical layers. The parataenial, paraventricular and intermediodorsal midline nuclei each project to circumscribed parts of the prefrontal cortex and the hippocampal and parahippocampal regions. In the prefrontal cortex, the projections are restricted to the medial orbital, infralimbic, ventral prelimbic and agranular insular fields, and the rostral part of the ventral anterior cingular cortex. In contrast to the other midline nuclei, the rhomboid nucleus projects to widespread cortical areas. The rostral intralaminar nuclei innervate dorsal parts of the prefrontal cortex, i.e. the dorsal parts of the prelimbic, anterior cingular and dorsal agranular insular cortical fields, the lateral and ventrolateral orbital areas, and the caudal part of the ventral anterior cingular cortex. Additional projections are aimed at the agranular fields of the motor cortex and the caudal part of the parietal cortex. The lateral part of the parafascicular nucleus sends fibres predominantly to the lateral agranular field of the motor cortex and the rostral part of the parietal cortex. The medial part of the parafascicular nucleus projects rather sparsely to the dorsal part of the prelimbic cortex, the anterior cingular cortex and the medial agranular field of the motor cortex. Individual midline and intralaminar thalamic nuclei are thus in a position to directly influence circumscribed areas of the cerebral cortex. In combination with previously reported data on the organization of the midline and intralaminar thalamostriatal projections and the prefrontal corticostriatal projections the present results suggest a high degree of differentiation in the convergence of thalamic and cortical afferent fibres in the striatum. Each of the recently described parallel basal ganglia-thalamocortical circuits can thus be expanded to include projections at both the cortical and striatal levels from a specific part of the midline and intralaminar nuclear complex. The distinctive laminar distributions of the fibres originating from the different nuclei emphasize the specificity of the midline and intralaminar thalamocortical projections.

Animals↗

Parabrachial nucleus projections to midline and intralaminar thalamic nuclei of the rat.

The projections from the parabrachial nucleus to the midline and intralaminar thalamic nuclei were examined in the rat. Stereotaxic injections of the retrograde tracer cholera toxin-beta (CTb) were made in each of the intralaminar nuclei of the dorsal thalamus (the lateral parafascicular, medial parafascicular, oval paracentral, central lateral, paracentral, and central medial nuclei), as well as the midline thalamic nuclei (the paraventricular, intermediodorsal, mediodorsal, paratenial, rhomboid, reuniens, parvicellular part of the ventral posterior, and caudal ventral medial nuclei). The retrograde cell body labeling pattern within the parabrachial subnuclei was then analyzed. The paracentral thalamic nucleus received an input only from the internal lateral parabrachial subnucleus. However, this subnucleus also projected to all the other intralaminar thalamic nuclei, except for the central lateral thalamic nucleus, which received no parabrachial afferent inputs. The external lateral parabrachial subnucleus projected to the lateral parafascicular, reuniens, central medial, parvicellular part of the ventral posterior, and caudal ventromedial thalamic nuclei. Following CTb injections in the paraventricular thalamic nucleus, retrogradely labeled cells were found in the central lateral, dorsal lateral, and external lateral parabrachial subnuclei. The medial and ventral lateral parabrachial subnuclei projected to the oval paracentral, parafascicular, and rhomboid thalamic nuclei. Finally, the waist area of the parabrachial nucleus was densely labeled after CTb injections in the parvicellular part of the ventral posterior thalamic nucleus. Nociceptive, visceral, and gustatory signals may reach specific cortical and other forebrain sites via this parabrachial-thalamic pathway.

Animals↗

Cholinergic and non-cholinergic projections from the canine pontomesencephalic tegmentum (Ch5 area) to the caudal intralaminar thalamic nuclei.

The distribution and morphology of cholinergic and non-cholinergic neurons projecting to the caudal intralaminar thalamic nuclei from the Ch5 area in the dog were examined using a technique combining horseradish peroxidase (HRP) retrograde labeling with choline acetyltransferase (ChAT) immunocytochemistry. After processing for ChAT, cholinergic neurons were found primarily within the nucleus tegmenti pedunculopontinus (PPN) and the central tegmental tract (ctt). ChAT positive neurons were also located in the nucleus cuneiformis and among the fibers of the lateral lemniscus and medial longitudinal fasciculus. On the basis of immunocytochemical and cytoarchitectonic data, PPN was divided into two distinct cell groups - a compact cell group located dorsolateral to the brachium conjunctivum and a diffuse cell group intermingled among the fibers of the brachium conjunctivum. Tissue processed for WGA-HRP and ChAT following injections of lectin-conjugated horseradish peroxidase into either the centrum medianum (CM) or parafascicular (Pf) nucleus resulted in double labeled cholinergic projection neurons in both PPN and ctt. Injections which involved CM and the caudal part of the central lateral thalamic nucleus (CL) resulted in more retrogradely labeled neurons than did those injections involving Pf. Injections of CM and CL also resulted in more double labeled cells in the dorsolateral compact portion of PPN than did injections confined to Pf. In all cases a small number of cholinergic neurons located in the contralateral PPN were retrogradely labeled as well. A substantial number of retrogradely labeled neurons were not ChAT positive, and in some cases, comprised up to 27% of the total population of projection neurons. Measurements of cell soma areas indicated that cells comprising the general cholinergic population were mostly medium (300-600 micrograms2) or large (greater than 600 micrograms2) in size. The majority of cholinergic projection neurons fell within the medium size category while the noncholinergic projection neurons were significantly smaller than their cholinergic counterparts. The results of this study suggest that in the dog, Ch5 cholinergic neurons which project to the caudal intralaminar thalamic nuclei are medium in size and are located primarily within PPN and ctt. In addition, a parallel projection to the caudal intralaminar nuclei exists which originates from smaller, non-cholinergic neurons in these same regions. Based on the results of this study, it appears that cholinergic projections to intralaminar thalamic nuclei which in turn project to the neostriatum may be one of the pathways over which PPN can affect basal ganglia activity.

Animals↗

Superior colliculus projections to midline and intralaminar thalamic nuclei of the rat.

The superior colliculus (SC) projections to the midline and intralaminar thalamic nuclei were examined in the rat. The retrograde tracer cholera toxin beta (CTb) was injected into one of the midline thalamic nuclei-paraventricular, intermediodorsal, rhomboid, reuniens, submedius, mediodorsal, paratenial, anteroventral, caudal ventromedial, or parvicellular part of the ventral posteriomedial nucleus-or into one of the intralaminar thalamic nuclei-medial parafascicular, lateral parafascicular, central medial, paracentral, oval paracentral, or central lateral nucleus. After 10-14 days, the brains from these animals were processed histochemically, and the retrogradely labeled neurons in the SC were mapped. The lateral sector of the intermediate gray and white layers of the SC send axonal projections to the medial and lateral parafascicular, central lateral, paracentral, central medial, rhomboid, reuniens, and submedius nuclei. The medial sector of the intermediate and deep SC layers project to the parafascicular and central lateral thalamic nuclei. The paraventricular thalamic nucleus is innervated almost exclusively by the medial sectors of the deep SC layers. The superficial gray and optic layers of the SC do not project to any of these thalamic areas. The discussion focuses on the role these SC-thalamic inputs may have on forebrain circuits controlling orienting and defense (i.e., fight-or-flight) reactions.

Animals↗

Lesions of the frontal cortex, hippocampus, and intralaminar thalamic nuclei have distinct effects on remembering in rats.

Lesions of the intralaminar thalamic nuclei (ILn), the medial wall (MW) area of prefrontal cortex, and the hippocampus were compared and found to have distinct effects on delayed matching-to-sample (DMS) and delayed non-matching-to-sample (DNMS) tasks based on different types of stimulus cues. Hippocampal lesions impaired DNMS trained in a radial arm maze but had little effect on DMS trained with retractable levers or olfactory DNMS. MW lesions affected the DMS task but had limited effects on olfactory DNMS and radial arm maze DNMS. ILn lesions resulted in a more generalized pattern of impairment for radial maze tasks and (in previous studies) for the DMS and olfactory DNMS tasks. Only the hippocampal lesion was associated with a delay-dependent impairment. It is argued that ILn lesions disrupt remembering through their effects on the recurrent, feedback pathways that link functionally related areas of the basal ganglia and cortex.

Analysis of Variance↗

Intralaminar thalamic nuclei lesions: widespread impact on dopamine denervation-mediated cellular defects in the rat basal ganglia.

Intralaminar thalamic nuclei represent a major site of non-dopaminergic degeneration in Parkinson disease, but the impact of this degeneration on the pathophysiological functioning of basal ganglia remains unknown. To address this issue, we compared the effects of 6-hydroxydopamine-induced lesions of nigral dopamine neurons alone or combined with ibotenate-induced lesions of intralaminar thalamic neurons on markers of neuronal metabolic activity in the rat basal ganglia using in situ hybridization histochemistry. Thalamic lesions prevented most of the dopamine denervation-induced changes (i.e. the increases in mRNA levels of enkephalin and GAD67 in the striatum, of GAD67 in the globus pallidus and entopeduncular nucleus, and of cytochrome oxidase subunit-I in the subthalamic nucleus), but did not affect the downregulation of striatal substance P and upregulation of GAD67 in the substantia nigra pars reticulata. We also provide immunohistochemical evidence that thalamic lesions markedly decreased striatal expression of the vesicular glutamate transporter vGluT2, confirming the association of this transporter with the thalamic projections to the basal ganglia. Altogether, these data reveal a major antagonistic influence of thalamic and dopaminergic afferents onto the basal ganglia and suggest that degeneration of thalamic neurons in Parkinson disease may represent an important factor counteracting expression of the defects associated with the dopamine denervation.

Adrenergic Agents↗

Spinal neuronal collaterals to the intralaminar thalamic nuclei and periaqueductal gray.

The existence of spinal neuron collaterals projecting to the intralaminar thalamic nuclei (ILN) and the periaqueductal gray (PAG) was determined in the rat using double-labeling, fluorescent, retrograde axoplasmic transport techniques. Distinctively double-labeled neurons, although not numerous, were found in the entire extent of the spinal cord. More double-labeled neurons were observed in the lumbosacral enlargement than in other cord segments. The laminar origin of the ILN and PAG projecting neurons were found primarily in the contralateral reticular portion of V, medial VII and the nucleus of dorsolateral funiculus. In addition, ipsilateral lateral cervical and central cervical nuclei also exhibited double-labeled neurons. This finding suggests that the pathway of medial thalamus projecting to the paleospinothalamic tract is very complex because the tract has triple connections, i.e. direct, collateral and indirect.

Afferent Pathways↗

Abnormal neuroneal activities in intralaminar thalamic nuclei following chronic lesions of nucleus reticularis thalami in rats.

Extracellular single unit activity in the intralaminar thalamic nuclei (ncl. centralis lateralis, CL, n = 77 and ncl. parafascicularis, Pf, n = 163) and in the pretectal area (Pt, n = 75) was examined following chronic electrolytic lesions of the nucleus reticularis thalami (nRT) in ketamine-anaesthetized rats after single electrical stimuli to the ventrobasal complex (VB). Extensive alterations of either the ongoing ("spontaneous") activity or the pattern of VB evoked responses were observed. Four major changes were observed in the activity of these intralaminar or pretectal neurones: 1) many neurones were silent, two times more frequently than in a parallel study with control intact rats; 2) the firing pattern of all the other neurones was in the form of tonic (stationary-like) discharge, without burst discharges as previously described in intact animals. They were ranked into classes according to their spontaneous discharge: class I, silent (no resting discharge) 12%, class II (1-15 Hz), 54 % and class III (> 16 Hz), 34%. Class III neurones were never found in intact rats; 3) electrical stimulation of the VB evoked a short latency orthodromic excitatory response in these neurones but this response was not followed by any slowing or depression of the spontaneous activity in more than 40% of recorded cells. When it occurred, this pause was shorter than that always observed in intact rats by more than 35% and longer in 7% of the responsive cells. All these changes were correlated with the extent of damage to the ipsilateral nRT; 4) VB stimulation evoked prolonged excitatory responses lasting more than 150 ms in 13% of the responsive cells, and nRT stimulation led to a short latency response followed by a pause of activity. These findings suggest that the nRT is involved in sensory integration and modulation.

Animals↗

Spontaneous neuronal hyperactivity in the medial and intralaminar thalamic nuclei of patients with deafferentation pain.

Electrical activity was recorded from single cells in the thalamus of 10 patients with chronic pain associated with deafferentation. Under local anesthesia, these patients underwent either electrode implantation or thalamotomy for treatment of their pain. In eight of the 10 patients, single units were identified as discharging spontaneously in high-frequency, often rhythmic, bursts. The discharges were of two types: short bursts comprised of two to six spikes with a burst frequency of one to four per second; and long trains of 30 to 80 spikes of similar frequency. Reconstruction of electrode trajectories indicated that recordings were made from the region corresponding to the lateral aspect of the mediodorsal thalamic nucleus, the central lateral nucleus, a small part of the central median nucleus, and the parafascicular nucleus. In the eight patients in whom spontaneous neuronal burst activity was exhibited, it was impossible to study activity evoked by natural cutaneous stimulation due to the continuous spontaneous neuronal discharges. Both animal and human studies have suggested that pain related to deafferentation is accompanied by spontaneous hyperactivity in the dorsal horn of the spinal cord and in the ventral posterior thalamic nuclei. The authors present evidence of spontaneous neuronal hyperactivity in the intralaminar thalamic nuclei of patients with pain related to deafferentation. The findings suggest that spontaneous neuronal discharge in patients with pain related to deafferentation is more widespread in the central nervous system than has been previously appreciated. The results have important implications for the surgical treatment of chronic pain.

Afferent Pathways↗

Effects of intralaminar thalamic nuclei lesion on glutamic acid decarboxylase (GAD65 and GAD67) and cytochrome oxidase subunit I mRNA expression in the basal ganglia of the rat.

This study investigated the influence of thalamic inputs on neuronal metabolic activity in the rat basal ganglia. By means of in situ hybridization histochemistry, we examined the consequences of ibotenate-induced unilateral lesion of intralaminar thalamic nuclei on mRNA expression of cytochrome oxidase subunit-I (CoI) in the striatum and the subthalamic nucleus (STN) and of the two isoforms of glutamate decarboxylase (GAD65 and GAD67) in the striatum, globus pallidus (GP), entopeduncular nucleus (EP) and substantia nigra pars reticulata (SNr). In the striatum, GAD67 mRNA expression decreased selectively in the rostral part of the structure at 5 and 12 days postlesion (approximately -30%), whereas, GAD65 mRNA levels was downregulated only in the caudal striatum at 12 days (-29%). In both the striatum and STN, CoI mRNA expression decreased ipsilaterally at 5 and bilaterally at 12 days. In GP, GAD67 and GAD65 mRNA expression decreased ipsilaterally at 5 (-20% and -26%) and 12 days (-23% and -36%). In EP, selective bilateral decreases in GAD67 mRNA expression were found at 5 and 12 days (-50% and -40%). Conversely, in SNr, only GAD65 mRNA expression was reduced bilaterally at both time points. These data show that the thalamus exerts a widespread excitatory influence on the basal ganglia network that cannot be accounted for solely by its known direct connections. Given the recent data showing that intralaminar thalamic nuclei are a major nondopaminergic site of neurodegeneration in Parkinson's disease, these results may have a critical bearing on understanding the cellular basis of basal ganglia dysfunction in parkinsonism.

Animals↗

Periaqueductal gray matter projections to midline and intralaminar thalamic nuclei of the rat.

The periaqueductal gray matter (PAG) projections to the intralaminar and midline thalamic nuclei were examined in rats. Phaseolus vulgaris-leucoagglutinin (PHA-L) was injected in discrete regions of the PAG, and axonal labeling was examined in the thalamus. PHA-L was also placed into the dorsal raphe nuclei or nucleus of Darkschewitsch and interstitial nucleus of Cajal as controls. In a separate group of rats, the retrograde tracer cholera toxin beta-subunit (CTb) was injected into one of the intralaminar thalamic nuclei-lateral parafascicular, medial parafascicular, central lateral (CL), paracentral (PC), or central medial nucleus-or one of the midline thalamic nuclei-paraventricular (PVT), intermediodorsal (IMD), mediodorsal, paratenial, rhomboid (Rh), reuniens (Re), or caudal ventral medial (VMc) nucleus. The distribution of CTb labeled neurons in the PAG was then mapped. All PAG regions (the four columns of the caudal two-thirds of the PAG plus rostral PAG) and the precommissural nucleus projected to the rostral PVT, IMD, and CL. The ventrolateral, lateral, and rostral PAG provided additional inputs to most of the other intralaminar and midline thalamic nuclei. PAG inputs to the VMc originated from the rostral and ventrolateral PAG areas. In addition, the lateral and rostral PAG projected to the zona incerta. No evidence was found for a PAG input to the ventroposterior lateral parvicellular, ventroposterior medial parvicellular, caudal PC, oval paracentral, and reticular thalamic nuclei. PAG --> thalamic circuits may modulate autonomic-, nociceptive-, and behavior-related forebrain circuits associated with defense and emotional responses.

Animals↗

Rat intralaminar thalamic nuclei projections to the globus pallidus: a biotinylated dextran amine anterograde tracing study.

The topographical organization and ultrastructural features of the intralaminar thalamic nuclei (ITN) projections to the globus pallidus (GP) were studied using the biotinylated dextran amine (BDA) anterograde tracing method in the rat. To assess the functional association of BDA injection sites in the ITN, the known topographical organization of the ITN-neostriatal (Str) projections and calcium binding protein (CaBP) immunostaining patterns of the Str and GP were used. BDA injection in the lateral part of the lateral parafascicular nucleus and the caudal part of the central lateral nucleus labeled fibers and boutons mainly in the dorsolateral sensorimotor territory of the Str and the middle territories of the GP. BDA injection in the medial part of the lateral parafascicular nucleus and the central lateral nucleus labeled mainly the middle association territory of the Str and the border and the caudomedial territories of the GP. BDA injection in the medial parafascicular nucleus and the central medial nucleus labeled mainly the medial limbic territory of the Str. The medial parafascicular nucleus projected to the medial-most region of the GP, while the central medial nucleus projection to the GP was very sparse. Electron microscopic observations indicated that BDA-labeled boutons form asymmetric synapses mainly on 0.5-2.0 microm diameter dendritic shafts in the GP. The boutons were small but had a relatively long active zone. The present observations together with the known topographical organization of striatopallidal projections indicated that the ITN-GP projections were topographically organized in parallel to the ITN-Str projections. Thus, each part of the ITN projecting to the sensorimotor, the association, and the limbic territories of the Str also projects to the corresponding functional territories of the GP.

Animals↗