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PubMed2000

Irregular jerky tremor, myoclonus, and thalamus: a study using low-frequency stimulation.

High-frequency thalamic stimulation alleviates tremor in Parkinson's disease (PD) and essential tremor (ET). The origin of thalamic myoclonus is unexplained and the effects of low-frequency thalamic stimulation on movement control are still unknown. We studied the effects of stimulation at a low frequency of 15 Hz in five drug-free patients (3 PD, 2 ET) 6 months after thalamic implantation of quadripolar electrodes (unilateral in four patients, bilateral in one patient). Clinical, electrophysiological, and videotaped assessment, using a monopolar 15 Hz frequency (3 V, 90 micros) stimulation current applied simultaneously through two adjacent contacts of the electrode, was performed. We observed myoclonus and irregular jerky tremor in the upper limb contralateral to the site of stimulation. The jerks lasted less than 200 ms, were irregular and not synchronous with stimulation, were superimposed on rest or postural tremor, and increased in response to tactile, proprioceptive, or vibratory stimuli. The fact that this complex movement disorder can be induced by low-frequency stimulation in the ventral intermediate nucleus (Vim) of the thalamus suggests that it results, at least partly, from dysfunction of the Vim and possibly adjacent nuclei of the thalamus.

Aged↗
PubMed1980

A quantitative comparison of the hominoid thalamus: II. Limbic nuclei anterior principalis and lateralis dorsalis.

Structures in the limbic system are commonly thought to be similar in form and function in all mammalian brains. In the study reported here, two thalamic limbic nuclei, N. anterior principalis and N. lateralis dorsalis, were compared among a group of extant hominoids. The nuclear volumes, neuronal densities, numbers of neurons per nucleus, and columes of neuronal perikarya were measured. Humans have much larger nuclei but the nuclei constitute a similar proportion of the whole thalamus as found in the other hominoids. Whereas the human limbic nuclei were observed to have a decrease in the densities of nerve cells compared with those of the other hominoids, this difference is less than that found in most other thalamic nuclei. Consequently the estimated number of neurons is much higher for humans. The total number of neurons best separates the human limbic nuclei from those of the other hominoids. This preliminary study suggests that during hominid evolution neurons were preferentially added to the limbic nuclei of the thalamus.

Adult↗
PubMed2001

Nigrostriatal collaterals to thalamus degenerate in parkinsonian animal models.

Movement, cognition, emotion, and positive reinforcement are influenced by mesostriatal, mesocortical, and mesolimbic dopamine systems. We describe a fourth major pathway originating from mesencephalic dopamine neurons: a mesothalamic system. The dopamine transporter, specific to dopamine containing axons, was histochemically visualized in thalamic motor and limbic-related nuclei and regions that modulate behavioral state as opposed to sensory nuclei in rats, nonhuman primates, and humans. Anatomical tracing established this innervation's origin via axon collaterals from the mesostriatal pathway. These findings implicate the thalamus as a novel site for disease specific alterations in dopamine neurotransmission, such as exist with nigral degeneration attending Parkinson's disease. This was confirmed in hemiparkinsonian animals where reduction of thalamic dopamine innervation occurred coincident with signs of active axonal degeneration. Individual mesencephalic dopamine neurons therefore have the potential to modulate normal and pathologic behavior not only through traditional nigrostriatal pathways but also by way of axon collaterals that innervate the thalamus.

Animals↗
PubMed2003

Fine structural localization of connexin-36 immunoreactivity in mouse cerebral cortex and thalamus.

The mounting physiological evidence for low-resistance electrical coupling between thalamic and cortical neurons contrasts with a lack of morphological data on gap junctions in thalamus and cortex. Connexin-36 is a neuronally specific protein associated with low-resistance gap junctions in the central nervous system. Connexin-36 localization was studied in the mouse somatosensory cortex and thalamus by using immunocytochemistry and immunoelectron microscopy. Expression of connexin-36 immunoreactivity is widespread in the forebrain and significantly enhanced in the barrel cortex and thalamic reticular nucleus during the second postnatal week, but it extends to other thalamic nuclei as well. At the electron microscopic level, pre- and postembedding immunogold labeling revealed that 70-76% of connexin-36-immunolabeled particles were localized at focal sites on apposed plasma membranes of cortical and thalamic dendrites; approximately 5% of the particles were associated with parasynaptic membranes; but on no occasion could overt, morphologically identifiable gap junctions be demonstrated in association with connexin-36 immunoreactivity. The widespread distribution of focal concentrations of connexin-36 subunits could provide a basis for the electrical coupling that exists between cortical and reticular thalamic neurons, but morphologically definable gap junctions may be too small to be adequately visualized by conventional immunoelectron microscopy.

Animals↗
PubMed1976

Organization and morphologies of acetylcholinesterase-containing neurons in the thalamus and hypothalamus of the rat.

The distribution and morphologies of neurons containing acetyl cholinesterase (AChE, EC 3.1.1.7) in the thalamus and hypothalamus of the rat were studied by means of a pharmaco-histochemical technique involving staining for AChE (Karnovsky-Roots' procedure) at various times after administration of bis-(u-methylethyl)phosphorofluoridate. This method enables visualization of individual AChE-containing neuronal somata and their processes to a degree not possible with other protocols for the enyzme. The strongest AChE activity occurring at the level of the thalamus is found within the small, round to oval, somata of nucleus anterior dorsalis. Most of the intralaminar nuclei, as well as nucleus reticularis, are composed of medium-sized multipolar neurons displaying moderate to strong AChE activity. Moderately stained AChE neurons are also found in pars ventralis of nucleus geniculatus lateralis and in pars lateralis of nucleus habenularis. Most of the neurons of the lateral and posterior thalamic territories, however, are nearly devoid of AChE. At the level of the hypothalamus, the neurons of nuclei supraoptics and paraventricularis show strong AChE activity. The AChE neurons of nucleus supraopticus are surrounded by numerous AChE-containing processes of some large lateral preoptic area neurons that stain intensely for the enzyme. Numerous intensely stained AChE perikarya occur in the lateral, dorsal, and supra-mammillary hypothalmic areas. These neurons often possess several AChE-containing processes. Nuclei arcuatus and ventomedialis consist mainly of neurons displaying a weak to moderate intensity of AChE staining. At the level of the mamillary bodies most neurons show moderate AChE activity except the neuronal somata of nucleus mammillaris lateralis which stain very strongly for the enzyme.

Acetylcholinesterase↗
PubMed1977

Topographic organization of the projections from cortical areas 17, 18 and 19 onto the thalamus, pretectum and superior colliculus in the cat.

The distribution of cortical projections from areas 17, 18 and 19 to the lateral thalamus, pretectum, and superior colliculus was investigated with the autoradiographic tracing method. Cortical areas 17, 18 and 19 were demonstrated to project retinotypically and in register upon the dorsal lateral geniculate nucleus, medial interlaminar nucleus, lateral zone of the lateral posterior complex, nucleus of the optic tract and superior colliculus. Area 19 was shown to project retinotopically upon the pulvinar nucleus. Clear retinotopic organization was not demonstrable in the projections of areas 17, 18 and 19 to the reticular complex of the thalamus and ventral lateral geniculate nucleus, or in the projection of area 19 to the anterior pretectal nucleus. The cortical projections were employed to define the retinotopic organization of the nucleus of the optic tract, pulvinar nucleus, and later zone of the lateral posterior complex. The cortical projections show the vertical meridian to be represented caudally, with the lower visual field represented laterally, and the upper visual field medially, within the nucleus of the optic tract. The projections of area 19 to the pulvinar nucleus demonstrate the lower visual field to be represented rostrally and the upper field caudally in this mucleus; the vertical meridian to be represented at the lateral border and the visual field periphery to be represented at the medial border of the pulvinar nucleus. Cortical projections to the lateral zone of the lateral posterior complex demonstrate the lower visual field to be represented rostrally and the upper visual field caudally; the vertical meridian to be represented at the medial limit and the visual field periphery at the lateral border of the termination zones. On the basis of the experimental findings a new terminology is introduced for the feline lateral posterior complex. Divisions are proposed which correspond to zones with demonstrably distinct afferent input. The pulvinar nucleus is defined by the distribution of projections from area 19. Three flanking divisions are defined within the lateral posterior complex; a lateral division recipient of projections from area 17, 18 and 19, and interjacent division recipient of projections of the superficial layers of the superior colliculus, and a medial division flanking the tectorecipient zone medially.

Animals↗
PubMed1984

Projections of the amygdala to the thalamus in the cynomolgus monkey.

The projections of the amygdala to the thalamus in cynomolgus monkeys (Macaca fascicularis) were studied with both anterograde and retrograde axonal tracing techniques. Horseradish peroxidase (HRP) was injected into medial and midline thalamic sites in five animals, and tritiated amino acids were injected into selected amygdaloid regions in a total of 13 hemispheres in ten animals. The findings from the two types of tracer experiments demonstrated the origins, course, and terminal pattern of amygdaloid projections to two thalamic nuclei--medialis dorsalis (MD) and reuniens. Almost all of the amygdaloid nuclei contribute projections to MD, though the greatest proportion arise from the basal group and terminate in discrete, interlocking patches within the medial, magnocellular portion of MD. In addition to this major projection, the central and medial amygdaloid nuclei send a lighter projection to the lateral portion of nucleus reuniens. The amygdalothalamic projections took a variety of routes out of the amygdala before the large majority joined the inferior thalamic peduncle and entered the rostral head of the thalamus where they turned caudally toward their targets. A small number of amygdalothalamic fibers may also run in the stria terminalis.

Amygdala↗
PubMed1985

Vibrissae tactile stimulation: (14C) 2-deoxyglucose uptake in rat brainstem, thalamus, and cortex.

The right mystacial vibrissae of awake, adult rats were stroked at 4-6 times/second and brain regions which increased (14C) 2-deoxyglucose (2DG) uptake were mapped autoradiographically. The ventral parts of the ipsilateral spinal trigeminal nuclei pars caudalis (Sp5c), pars interpolaris (Sp5i), pars oralis (Sp5o), and the principal trigeminal sensory (Pr5) nuclei were activated. The lateral part of the ipsilateral facial (VII) nucleus (the region which innervates the vibrissae muscles) was also activated possibly via excitatory, trigeminal (Sp5c, Sp5i, Sp5o, Pr5) sensory afferents. A number of regions were activated contralateral to the sensory stimulus. Discrete patches of (14C) 2DG uptake occurred in deep layers of the superior colliculus (SCsgp). Dorsolateral and dorsomedial parts of the ventrobasal nucleus (VB), and posterior, dorsolateral parts of the reticular nucleus (R) of thalamus were activated, along with broad portions of the primary somatosensory cortex (SI) and second somatosensory cortex (SII). Though all layers of SI and SII cortex increased 2DG uptake, VB thalamic afferents to layers IV and Vc-Vla presumably accounted for the greater activation of these cortical layers during repetitive sensory stimulation of the vibrissae (RSSV). Activation of the above structures fits well with known anatomical data. However, the pattern of activation during RSSV was very different from that previously described during vibrissae motor cortex stimulation (VMIS). RSSV and VMIS both produced similar repetitive movements of all the mystacial vibrissae. However, only a few overlapping brain regions were activated during both RSSV and VMIS. These RSSV-VMIS overlap zones included Sp5o; rostral Sp5i; lateral VII; SCsgp; ventrobasal-posteromedial and ventrobasal-ventrolateral zones in thalamus; and a rostral region of SI probably anterior to the Woolsey vibrissae barrelfield in the dysgranular somatosensory (SI) cortex. Since RSSV and VMIS would both be expected to activate vibrissae proprioceptors, we have hypothesized that vibrissae proprioceptive input was processed in part in the RSSV-VMIS overlap zones. Convergence of motor-sensory inputs and other types of processing could have also occurred in these overlap zones.

Animals↗
PubMed1985

Light and electron microscopic evidence of transneuronal labeling with WGA-HRP to trace somatosensory pathways to the thalamus.

Horseradish peroxidase conjugated to wheat-germ lectin is being used with increasing frequency as an anterograde label to trace pathways in the nervous system, owing to the sensitivity of the method and ease of use. However, it has been suggested that horseradish peroxidase conjugated to wheat-germ lectin may be transneuronally transported, thus affecting the ease of interpretation of the results. The present study used the projections of the dorsal column nuclei and spinal cord to the thalamus as a model system to determine whether transneuronal transport could be demonstrated and whether the degree of such transport was related to the size of the injection site. Light microscopic observation of sections incubated with tetramethyl benzidine after large injections (1 microL of a 10% solution of horseradish-peroxidase-conjugated wheat-germ lectin in water) in the dorsal column nuclei demonstrated the presence of labeled neurons in the nucleus reticularis thalami, which is not known to receive afferents from or project to these nuclei. The electron microscopic study, although based upon the use of the chromogen benzidine dihydrochloride, less sensitive than tetramethyl benzidine, revealed the existence of labeled neurons in the thalamic ventrobasal complex. This is unlikely to be due to retrograde labeling and is therefore interpreted as a result of transneuronal, perhaps transsynaptic, transport. Glial and perivascular cells also contained granules of reaction product in some cases. Smaller injections (100 nL) in the dorsal column nuclei, on the other hand, did not produce this apparent transneuronal labeling. After small injections (100 nL) in the spinal cord, anterograde labeling was observed mainly in the thalamic ventrobasal complex in the rat, and in the posterior group in the cat, and the nuclei centralis lateralis and submedius in both species, as has been described in numerous other studies. After large injections, additional labeled areas were observed in the posterior intralaminar region (parafascicular-center median complex), in the medial thalamus (nuclei reuniens, rhomboid and paraventricular), and in the cat, in the ventroposterolateral nucleus. In the rat, experiments were performed in which a kainic acid injection was made to induce neuronal loss in the nucleus reticularis gigantocellularis of the medulla, which is a relay of the spinoreticulothalamic pathway, known to project to some of these thalamic areas.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1987

Organization of postcranial kinesthetic projections to the ventrobasal thalamus in raccoons.

To determine the presence and organization of kinesthetic, as compared with other mechanosensory projection zones in the thalamus of raccoons, unit-cluster responses to mechanical stimulation of the postcranial body were mapped electrophysiologically in the thalami of 14 raccoons anesthetized with Dial-urethane. A distinct zone of kinesthetic projections (from receptive fields in muscles, tendons, and joints) was found in the rostral and dorsal aspects of the mechanosensory projection zone. These projections are somatotopically organized: those from axial structures lie dorsalmost and those from successively more distal limb regions are successively more caudoventral. The kinesthetic forelimb representation is large and lies rostrodorsal to a large central core of cutaneous projections from the forepaw digits. A few scattered kinesthetic projections were found at the caudal edge of the sensory thalamic region. The large, spatially and somatotopically distinct kinesthetic projection zone in the thalamus parallels those seen in the cortex and medulla of raccoons. Similar findings in monkeys, and suggestions from data in cats and humans support the hypothesis of a distinct pathway to the cortex for kinesthetic information in all mammals.

Afferent Pathways↗
PubMed1988

Basal forebrain cholinergic and noncholinergic projections to the thalamus and brainstem in cats and monkeys.

The projections of basal forebrain neurons to the thalamus and the brainstem were investigated in cats and primates by using retrograde transport techniques and choline acetyltransferase (ChAT) immunohistochemistry. In a first series of experiments, the lectin wheat germ-agglutinin conjugated with horseradish peroxidase (WGA-HRP) was injected into all major sensory, motor, intralaminar, and reticular (RE) thalamic nuclei of cats and into the mediodorsal (MD) and pulvinar-lateroposterior thalamic nuclei of macaque monkeys. In cats numerous neurons of the vertical and horizontal limbs of the diagonal band nucleus and the substantia innominata (SI), including its rostromedial portion termed the ventral pallidum (VP), were retrogradely labeled after WGA-HRP injections in the rostral pole of the RE complex, the MD, and anteroventral/anteromedial (AV/AM) thalamic nuclei. Fewer retrogradely labeled cells were observed in the same areas after injections in the ventromedial (VM) thalamic nucleus, and none or very few after other thalamic injections. After RE, MD, and AV/AM injections, 7-20% of all retrogradely labeled cells in the basal forebrain were also ChAT positive, while none of the retrogradely labeled neurons following VM injections displayed ChAT immunoreactivity. The basal forebrain projection to the MD nucleus was shown to arise principally from VP in both cats and macaque monkeys. In a second series of experiments performed in cats, injections of WGA-HRP in the brainstem peribrachial (PB) area comprising the pedunculopontine nucleus led to retrograde labeling of a moderate number of neurons in the lateral part of the VP, SI, and preoptic area (POA), only a few of which displayed ChAT immunoreactivity. In addition, a large number of retrogradely labeled cells were observed in the bed nuclei of the anterior commissure and stria terminalis after PB injections. In a third series of experiments, the use of the retrograde double-labeling method with fluorescent tracers in squirrel monkeys allowed us to identify a significant number of basal forebrain neurons sending axon collaterals to both the RE thalamic nucleus and PB brainstem area, while no double-labeled neurons were disclosed after injections confined to the ventral anterior/ventral lateral (VA/VL) thalamic nuclei and PB area or following injections in the cerebral cortex and PB area. Our findings reveal the existence of cholinergic and noncholinergic basal forebrain projections to the thalamus and the brainstem in both cats and macaque monkeys. We suggest that these projections may play a crucial role in the control of thalamic functions in mammals.

Animals↗
PubMed1991

Transient retinal axon collaterals to visual and somatosensory thalamus in neonatal hamsters.

We have studied the postnatal development of individual axons in the optic tract and thalamus of the Syrian hamster, concentrating attention on retinal ganglion cell axons that make a transient projection to the main somatosensory nucleus, the ventrobasal complex. We bulk-filled axons with horseradish peroxidase in hemithalami maintained en bloc, in vitro. After processing and reaction with diaminobenzidine, we reconstructed individual axons from serial sections. In hamsters and other rodents, the optic tract is composed of superficial and internal components, either or both being possible sources of the retino-ventrobasal projection. Both project to the midbrain, but in normal adults only the superficial optic tract maintains collaterals in the thalamus. We found that the axons of the internal component bear numerous transient thalamic collaterals on postnatal days 0, 1, and 2, and some of these extend into the ventrobasal complex. Axons in the superficial optic tract also bear collaterals on days 0 to 2, but these are confined to the superficial half of the dorsal lateral geniculate nucleus. Thus the transient retino-ventrobasal projection comprises solely transient collaterals originating from axon trunks in the internal optic tract. On days 1 and 2, some collaterals from the superficial optic tract appear to have begun to arborize in the lateral geniculate nucleus. In contrast, collaterals from internal optic tract axons to the ventrobasal complex branch little if at all as they traverse the lateral geniculate nucleus, and at no time prior to their elimination do they develop an appreciable terminal arbor. These long collaterals often terminate in growth cones that include lamellopodia. Our HRP-impregnation method also revealed some transient non-retinofugal axons that pass medially from the ventral lateral geniculate nucleus to the ventrobasal complex but then return without terminating or branching. By day 4, they are absent, as are collaterals from the internal optic tract to the ventrobasal complex.

3,3'-Diaminobenzidine↗
PubMed1995

Morphology of physiologically identified retinal X and Y axons in the cat's thalamus and midbrain as revealed by intraaxonal injection of biocytin.

Prior morphological studies of individual retinal X and Y axon arbors based on intraaxonal labeling with horseradish peroxidase have been limited by restricted diffusion or transport of the label. We used biocytin instead as the intraaxonal label, and this completely delineated each of our six X and 14 Y axons, including both thalamic and midbrain arbors. Arbors in the lateral geniculate nucleus appeared generally as has been well documented previously. Interestingly, all of the labeled axons projected a branch beyond thalamus to the midbrain. Each X axon formed a terminal arbor in the pretectum, but none continued to the superior colliculus. In contrast, 11 of 14 Y axons innervated both the pretectum and the superior colliculus, one innervated only the pretectum, and two innervated only the superior colliculus. Two of the Y axons were quite unusual in that their receptive fields were located well into the hemifield ipsilateral with respect to the hemisphere into which they were injected. These axons exhibited remarkable arbors in the lateral geniculate nucleus, diffusely innervating the C-laminae and medial interlaminar nucleus, but, unlike all other X and Y arbors, they did not innervate the A-laminae at all. In addition to these qualitative observations, we analyzed a number of quantitative features of these axons in terms of numbers and distributions of terminal boutons. We found that Y arbors contained more boutons than did X arbors in both thalamus and midbrain. Also, for axons with receptive fields in the contralateral hemifield (all X and all but two Y axons), 90-95% of their boutons terminated in the lateral geniculate nucleus; the other two Y axons had more of their arbors located in midbrain.

Animals↗
PubMed2001

Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor.

Our objective was to investigate the long-term safety and efficacy of unilateral deep brain stimulation (DBS) of the VIM nucleus of the thalamus in essential tremor. Forty-nine patients were evaluated for DBS between December 1993 and March 1998. Tremor was assessed by a clinical rating scale at 3 and 12 months and then yearly. Three patients were not implanted, seven were explanted prior to 24 months, 11 were lost to long-term follow-up, and three died from unrelated causes. Twenty-five patients were evaluated with follow-up greater than or equal to 2 years. The last postsurgical follow-up occurred on average 40.2 +/- 14.7 months after surgery. Tremor scores were significantly improved with stimulation on at the long-term follow-up as compared to baseline. There was no change in tremor scores from baseline to long-term follow-up with stimulation off. There was no significant change in any stimulus parameters from 3 months to the long-term follow-up. Three patients had asymptomatic intracerebral hemorrhages and one patient had postoperative seizures. Stimulus-related adverse reactions were mild and easily controlled with changes in stimulus parameters. Device-related complications were common and required repeated surgical procedures. Unilateral DBS of the thalamus has long-term efficacy in some patients for treatment of essential tremor. However, this therapy is compromised by loss of efficacy in some patients and device complications which increase the risk of additional surgical procedures.

Adult↗
PubMed2002

Improvement of severe trunk spasms by bilateral high-frequency stimulation of the motor thalamus in a patient with chorea-acanthocytosis.

We report on a patient with a severe form of chorea-acanthocytosis, intractable to medical treatment, who benefited from bilateral high-frequency stimulation (HFS) of the posterior ventral oral nucleus of the thalamus. The frequency of trunk spasms dramatically decreased after surgery and the clinical benefit remained stable 1 year later. However, no clear effect was observed on dysarthria nor on hypotonia, which always impaired gait. We propose that HFS of the motor thalamus is a potential treatment for choreic or truncal dystonic symptoms whenever hypotonia is not the main feature of the syndrome.

Adult↗
PubMed1998

The role of the thalamus and basal ganglia in parkinsonian tremor.

The mechanism of parkinsonian tremor may involve a central oscillator, peripheral feedback to the central nervous system (CNS), or both. The thalamus or the globus pallidus is the most likely site for a central oscillator and would be predicted to generate thalamic tremor-related activity characterized, respectively, by calcium spike-associated bursts and by maximal tremor-related activity in the pallidal relay nucleus of thalamus. Thalamic spike trains demonstrate neither of these characteristics. However, cross-correlation, latency, and transfer function analysis indicate that sensory feedback is a critical element in the relationship between thalamic activity and parkinsonian tremor. Therefore, thalamic spike train activity is most consistent with parkinsonian tremor being mediated by peripheral inputs involved in either an unstable reflex loop or sensory modulation of a central oscillator.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed2006

Expression of excitatory amino acid transporter interacting protein transcripts in the thalamus in schizophrenia.

The excitatory amino acid transporters (EAATs) are a family of plasma membrane proteins that maintain synaptic glutamate concentration by removing glutamate from the synaptic cleft. EAATs are expressed by glia (EAAT1 and EAAT2) and neurons (EAAT3 and EAAT4) throughout the brain. Glutamate reuptake is regulated, in part, by EAAT-interacting proteins that modulate subcellular localization and glutamate transport activity of the EAATs. Several lines of investigation support the hypothesis of glutamatergic abnormalities in schizophrenia. Previous work in our laboratory demonstrated increased expression of EAAT1 and EAAT2 transcripts in the thalamus, suggesting that alterations in synaptic glutamate levels may contribute to the pathophysiology of schizophrenia. Since EAAT-interacting proteins regulate EAAT function, directly impacting glutamatergic neurotransmission, we hypothesized that expression of EAAT-interacting proteins may also be altered in schizophrenia. Using in situ hybridization in subjects with schizophrenia and a comparison group, we detected increased expression of JWA and KIAA0302, molecules that regulate EAAT3 and EAAT4, respectively, in the thalamus in schizophrenia. In contrast, we did not find changes in the expression of transcripts for the EAAT2 and EAAT4 regulatory proteins GPS-1 and ARHGEF11. To address prior antipsychotic treatment in our schizophrenic subjects, we treated rats with haloperidol and clozapine for 4 weeks, and found changes in transcript expression of the EAAT-interacting proteins in clozapine-, but not haloperidol-, treated rats. These findings suggest that proteins associated with the regulation of glutamate reuptake may be abnormal in this illness, supporting the hypothesis of altered thalamic glutamatergic neurotransmission in schizophrenia.

Aged↗
PubMed1994

Extrusion transplantation of Schwann cells into the adult rat thalamus induces directional host axon growth.

In a previous study we found that Schwann cells microtransplanted into the central nervous system rapidly dispersed from the transplantation site and became intimately associated with host grey and white matter. We have now investigated whether this migratory behavior of the donor Schwann cells is compatible with the production of stable, continuous anatomical cell tracks and whether such tracks can induce directional host axon growth. During the gradual withdrawal of a micropipette, highly purified suspensions of cultured adult peripheral nerve Schwann cells were continuously extruded to form a vertical column of cells extending for up to 4 mm through the thalamus and across the choroid fissure into the hippocampus of adult rat hosts. The donor Schwann cells were identified by immunohistochemistry for low-affinity nerve growth factor receptor, vimentin, and Rat 401. Although donor Schwann cells migrated into the host tissues, a large number remained along the axis of the injection track to form a column which was maintained for up to 3 weeks. From 4 days, increasing numbers of parallel, unbranching host RT97-positive axons entered the Schwann cell column in alignment with the long axis of the Schwann cells in the vertical tracks. The axons did not fasciculate directly with each other, but mingled diffusely with the Schwann cells. The Schwann cell tracks were able to convey host axons out of the dorsal thalamus, across the extracellular space of the choroid fissure, and into the ventral hippocampus. Thus, Schwann cells, transplanted in the form of elongated tracks, can establish bridges across boundary membranes in the brain and carry substantial numbers of nerve fibers from one area to another.

Animals↗