Ventral Thalamic Nucleus Research Articles

Convergent Inputs from Thalamic Motor Nuclei and Frontal Cortical Areas to the Dorsal Striatum in the Primate

Current models of basal ganglia circuitry primarily associate the ventral thalamic nuclei with relaying basal ganglia output to the frontal cortex. However, some studies have demonstrated projections from the ventral anterior (VA) and ventral lateral (VL) thalamic nuclei to the striatum, suggesting that these nuclei directly modulate the striatum. VA/VL nuclei have specific connections with primary, supplementary, premotor, and cingulate motor cortices indicating their involvement in motor function. These areas mediate different aspects of motor control such as movement execution, motor learning, and sensorimotor integration. Increasing evidence indicates that functionally related motor areas have convergent projections to the dorsal striatum, suggesting that integration of different aspects of motor control occur at the level of the striatum. This study examines the organization of VA/VL thalamic inputs to the dorsal "motor" striatum to determine how this afferent projection is organized with respect to corticostriatal afferents from motor, premotor, and cingulate motor areas. Motor cortical projections to specific dorsal striatal regions arose from multiple areas, including components from primary motor, premotor, supplementary, and cingulate motor areas. Diverse motor cortical projections to a given dorsal striatal region indicated convergence of functionally related corticostriatal motor pathways. Most dorsal striatal sites received dense thalamic inputs from the VL pars oralis nucleus. Additional thalamostriatal projections arose from VA, VL pars caudalis, and ventral posterior lateral pars oralis nuclei and Olszewski's Area X. Our results provide evidence for convergent striatal projections from interconnected ventral thalamic and cortical motor areas, suggesting that these afferents modulate the same striatal output circuits.

An anterograde and retrograde tract-tracing study on the projections from the thalamic gustatory area in the rat: distribution of neurons projecting to the insular cortex and amygdaloid complex.

Projections from the thalamic gustatory nucleus, i.e. the parvicellular part of the posteromedial ventral thalamic nucleus (VPMpc) to the forebrain regions were studied in the rat by the tract-tracing methods with anterograde tracer (biotinylated dextran amine, BDA) and anterograde/retrograde tracer (wheat-germ agglutinin-horseradish peroxidase, WGA-HRP). After BDA injection into the VPMpc, terminal labeling was observed in the insular cortex, amygdaloid complex, and fundus striati. The terminal labeling in the amygdaloid complex was distributed in dorsolateral area of the rostral part of the lateral amygdaloid nucleus and the rostral part of the lateral subdivision of the central amygdaloid nucleus. The terminal labeling in the central amygdaloid nucleus extended to the fundus striati. The retrograde tracing study with WGA-HRP revealed that the projection fibers from the VPMpc to the amygdaloid complex originated from the medial part of the VPMpc and also from the thalamic area medial to the VPMpc. In the rats injected with Fluoro-Gold and WGA-HRP, respectively into the insular cortex and amygdaloid complex, no double-labeled neuronal cell bodies were found in the VPMpc, although neurons labeled singly with Fluoro-Gold were intermingled with those singly labeled with WGA-HRP in the medial part of the VPMpc. The results indicated that VPMpc neurons projecting to the amygdaloid complex constituted a population different from VPMpc neurons projecting to the insular cortex.

Comparative distribution of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites and PACAP receptor mRNAs in the rat brain during development

The distribution and density of pituitary adenylate cyclase-activating polypeptide (PACAP) binding sites as well as PACAP-specific receptor 1 (PAC1-R), vasoactive intestinal polypeptide/PACAP receptor 1 (VPAC1-R), and VPAC2-R mRNAs have been investigated in the rat brain from embryonic day 14 (E14) to postnatal day 8 (P8). Significant numbers of binding sites for the radioiodinated, 27-amino-acid form of PACAP were detected as early as E14 in the neuroepithelia of the metencephalon and the myelencephalon. From E14 to E21, the density of binding sites in the germinative areas increased by 3- to 5-fold. From birth to P12, the density of binding sites gradually declined in all neuroepithelia except in the external granule cell layer of the cerebellum, where the level of binding sites remained high during the first postnatal weeks. Only low to moderate densities of PACAP binding sites were found in regions other than the germinative areas, with the exception of the internal granule cell layer of the cerebellum, which contained a high density of sites. The localization of PACAP receptor mRNAs was investigated by in situ hybridization using [(35)S] uridine triphosphate-specific riboprobes. The evolution of the distribution of PAC1-R and VPAC1-R mRNAs was very similar to that of PACAP binding sites, the concentration of VPAC1-R mRNA being much lower than that of PAC1-R mRNA. In contrast, intense expression of VPAC2-R mRNA was observed in brain regions other than germinative areas, such as the suprachiasmatic, ventral thalamic, and dorsolateral geniculate nuclei. The discrete localization of PACAP binding sites as well as PAC1-R and VPAC1-R mRNAs in neuroepithelia during embryonic life and postnatal development strongly suggests that PACAP, acting through PAC1-R and/or VPAC1-R, may play a crucial role in the regulation of neurogenesis in the rat brain.

Changes in cerebral blood oxygenation of the frontal lobe induced by direct electrical stimulation of thalamus and globus pallidus: a near infrared spectroscopy study

OBJECTIVEBlood oxygenation level dependent (BOLD) contrast functional MRI images show activated cortical areas by detecting a reduced concentration of deoxyhaemoglobin (deoxy-Hb) during neuronal activity; however, near infrared spectroscopy (NIRS) has...

A morphometric study of subcortical changes in Alzheimer's disease

The populations and loss of neurons, the density of neurofibrillary tangles (NFT) and senile plaque (SP), and the macroscopic shrinkage of the subcortical areas in patients with Alzheimer's disease (AD) were quantitatively evaluated using computer‐based image analysis techniques. Twelve subcortical areas were examined at distinct levels of the brain in eight AD cases and five age‐matched controls. The areas examined were as follows: the nucleus basalis of Meynert (nbM); globus pallidus (GP); putamen (PT); claustrum (CL); the anterior thalamic nucleus (THA: anterior ventral thalamic nucleus); medial thalamic nucleus (THM: medio‐dorsal thalamic nucleus); lateral thalamic nucleus (THL: ventro‐lateral and ventro‐anterior thalamic nuclei); subthalamic nucleus (ST); substantia nigra, zona compacta (SNC); red nucleus (RD); locus ceruleus (LC); and raphe nucleus (RP). Distinct neuronal loss and a high density of NFT were shown in the nbM, LC, RP, CL, SNC, and THA in the AD brain. Because of the high density of the NFT relative to the neuronal loss, neuronal loss in those nuclei may have been mainly caused by NFT formation. In the THM and THL, no distinct neuronal loss but some degree of NFT formations was detected. In the GP, ST, and RD, neuronal shrinkage or loss was shown in patients with AD. With respect to the SP, the density of SP in the CL, PT and THM was high (1.7–2.2%), whereas that in the SNC, GP, ST and RD was low. This finding suggests that SP may not have major effects on the neuronal degeneration observed in subcortical nuclei of patients with AD. Although macroscopic shrinkage of all subcortical nuclei was seen in AD patients, selective vulnerability to atrophic change was not evident at macroscopic levels. This comprehensive morphometric study offers more precise information for evaluating the subcortical dysfunction in AD patients than do conven‐tional neuropathological examinations.

Differential effects of clozapine and haloperidol on ketamine-induced brain metabolic activation

Subanesthetic doses of N-methyl- d-aspartate (NMDA) receptor antagonists such as ketamine and phencyclidine precipitate psychotic symptoms in schizophrenic patients. In addition, these drugs induce a constellation of behavioral effects in healthy individuals that resemble positive, negative, and cognitive symptoms of schizophrenia. Such findings have led to the hypothesis that decreases in function mediated by NMDA receptors may be a predisposing, or even causative, factor in schizophrenia. The present study examined the effects of the representative atypical (clozapine) and typical (haloperidol) antipsychotic drugs on ketamine- induced increases in [ 14 C] -2-deoxyglucose (2-DG) uptake in the rat brain. As previously demonstrated, administration of subanesthetic doses of ketamine increased 2-DG uptake in specific brain regions, including medial prefrontal cortex, retrosplenial cortex, hippocampus, nucleus accumbens, basolateral amygdala, and anterior ventral thalamic nucleus. Pretreatment of rats with 5 or 10 mg/kg clozapine alone produced minimal or no change in 2-DG uptake, yet clozapine completely blocked ketamine-induced changes in 2-DG uptake in all brain regions studied. In striking contrast, a dose of haloperidol (0.5 mg/kg) that produces a substantial cataleptic response, potentiated, rather than blocked, ketamine-induced activation of 2-DG uptake. These results demonstrate, in a model with potential relevance to schizophrenia, a striking neurobiological difference between the actions of prototypical typical and atypical antipsychotic drugs. The dramatic blockade by clozapine of ketamine-induced brain metabolic activation suggests that antagonism of the consequences of reduced NMDA receptor function could contribute to the superior therapeutic effects of this atypical antipsychotic agent. The results also suggest that this model of ketamine-induced alterations in 2-DG uptake may be extremely useful for understanding the complex neural mechanisms of atypical antipsychotic drug action.

Trigeminal Projections to the Dorsal Thalamus in a Lacertid Lizard, Podarcis hispanica

Trigeminothalamic projections in the lizard Podarcis hispanica were investigated by means of biotinylated dextranamine (BDA) injections into different nuclei of the dorsal thalamus. Previous studies of lizards found a projection from the sensory trigeminal nuclei in the brainstem to the nuclei ventromedialis and ventrolateralis of the ventral thalamus. The present results show that, in addition to these projections to ventral thalamic nuclei, neurons of the nucleus of the descending tract and the principal sensory nucleus project contralaterally to the pretectal nucleus lentiformis thalami and bilaterally to the nucleus dorsolateralis anterior thalami of the dorsal thalamus. The contralateral projection to the nucleus dorsolateralis anterior is more developed than its ipsilateral counterpart and appears to be topographically organized. Since the nucleus dorsolateralis thalami has ascending projections to the cortex telencephali, this nucleus may be the thalamic relay of trigeminal sensory information to the telencephalon.

3H]-2-deoxyglucose uptake study in mutant dystonic hamsters: abnormalities in discrete brain regions of the motor system.

The genetically dystonic (dtSZ) hamster, an animal model of idiopathic paroxysmal dystonia, displays attacks of generalized twisting movements and abnormal postures of limbs and trunk either spontaneously or in response to mild stress. This experimental model may be helpful to give insights into the pathophysiology of idiopathic dystonia in man. In the present study, the regional uptake of [3H]-2-deoxyglucose (2-DG) was examined in brains (75 brain regions) of dtSZ hamsters during the expression of severe dystonia. 2-DG autoradiography revealed significant changes of 2-DG uptake in discrete brain regions of dtSZ hamsters compared with age-matched, nondystonic control hamsters. In dystonic hamsters, a dramatic increase of 2-DG uptake was observed in the red nucleus (159% over control). Furthermore, enhanced 2-DG uptake was found in the ventromedial, ventrolateral, and anteroventral nuclei of the thalamus (19-42%) and in the medial vestibular nucleus (23%). A significant decrease in 2-DG uptake in deep cerebellar nuclei (-30%) may be the result of decreased synaptic activity of GABAergic neurons within these structures resulting in enhanced excitatory output to red nucleus, thalamic, and vestibular nuclei. In dtSZ hamsters, the 2-DG uptake was not significantly altered overall within the basal ganglia. Significant increases of 14% were, however, found in discrete parts of the caudate putamen in which recent studies revealed changes of dopamine receptors. Altered neural activity within the basal ganglia may therefore contribute to increased 2-DG uptake in the ventral thalamic nuclei as well as to decreased 2-DG uptake (-13%) found in the reticular thalamic nucleus. Although the present data are in line with the concept that abnormal thalamocortical activity seems to be critically involved in the dystonic syndrome, altered activities in other motor areas than output structures of the basal ganglia, such as in the red nucleus, may contribute to clinical manifestation of dystonia in mutant hamsters.

Neuronal activity in the region of the thalamic principal sensory nucleus (ventralis caudalis) in patients with pain following amputations

Thalamic neuronal activity has not been studied in a primate model of peripheral nerve injury. We now report neuronal activity in the region of the human principal sensory nucleus of thalamus (ventralis caudalis) in awake patients during the physiologic exploration that precedes surgical procedures for treatment of stump pain and movement disorders. All patients with amputations showed increased thalamic representations of the stump as reflected in both receptive and projected field maps. This suggested that thalamic re-organization involved both the afferent inputs from and the perceptual representation of the limb. The spontaneous activity of neurons in the region of ventralis caudalis representing the limb with the stump (stump area) was significantly different from that in other areas of the region of ventralis caudalis in patients with amputations (stump control areas) and in patients with movement disorders (control areas). The mean interspike intervals were significantly shorter for cells located in stump areas than for those located in stump control or control areas. Cells in all areas were found to fire in three different patterns: B group (burst) characterized by bursting activity, R group (relay) characterized as a Poisson process, and III group characterized by non-bursting, non-Poisson activity. Cells in the B group were significantly more common in stump control (41%) and stump areas (33%) than in control areas (15%). Bursting cells were found to have patterns consistent with the occurrence of a calcium spike (spike-burst pattern). The spike-burst pattern was most common among cells with receptive fields in the stump area. In these cells firing between bursts (primary event rate) was significantly higher than other cells in the region of ventralis caudalis, suggesting that spike-bursts are not due to hyperpolarization, i.e. low-threshold spikes. Spike-bursts often occur as a result of low-threshold spikes, when the cell is hyperpolarized. In contrast, spike-bursts in these patients were associated with increased interburst firing rates in cells with receptive fields. Thus bursting of these cells may have been due to high-threshold dendritic calcium spikes evoked by afferent input. In that case bursting could be involved in activity-dependent changes in thalamic function following deafferentation through a calcium-mediated mechanism.

Lower density of A1 adenosine receptors in nucleus reticularis thalami in rats with genetic absence epilepsy.

The possible involvement of the adenosinergic modulatory system in the pathogenesis of absence seizures was investigated in genetic absence epilepsy rats from Strasbourg (GAERS). Using in vitro quantitative autoradiography, the distribution of A1 adenosine receptors and adenosine uptake sites in the brain of GAERS was studied and compared to that of control animals. An area-specific lower density of A1 receptors (15% decrease) was detected in reticular (nRT) and anterior ventral (AV) thalamic nuclei as well as basal ganglia in the brains of GAERS animals compared with control animals. Since adenosine exerts an anti-oscillatory effect on the thalamic nuclei by suppressing (via A1 receptors) excitatory as well as inhibitory neurotransmitter release, the impairment in A1 receptor density seen here, especially in nRT, could be implicated in the thalamic rhythmicity underlying spike and wave discharges present in this absence epilepsy model.

PEP-19 immunohistochemistry defines the basal ganglia and associated structures in the adult human brain, and is dramatically reduced in Huntington's disease

We have investigated the distribution of PEP-19, a neuron-specific protein, in the adult human brain. Immunohistochemistry for PEP-19 appears to define the basal ganglia and related structures. The strongest immunoreactivity is seen in the caudate nucleus and putamen, each of which showed both cell body and neuropil PEP-19 immunoreactivity The substantia nigra and both segments of the globus pallidus showed PEP-19 immunoreactivity only in the neuropil. Cell bodies and dendrites of the thalamic nuclei ventralis lateralis and ventralis anterioralis were less strongly immunoreactive. Cerebellar Purkinje cells and their dendrites were immunoreactive, as were the presubiculum/subiculum regions and dentate gyrus granule cells of the hippocampus. The CA zones of the hippocampus were not immunoreactive. Preliminary data from immunoblotting experiments indicate that PEP-19 immunoreactivity is significantly reduced in cerebellum in Alzheimer's disease. While there were no apparent alterations of immunoreactivity in Down's syndrome or in Parkinson's disease, immunohistochemical analysis showed a massive loss of PEP-19 immunoreactivity in the caudate nucleus, putamen, globus pallidus and substantia nigra in Huntington's disease. These results show that PEP-19, a neuron-specific, calmodulin-binding protein, is distributed in specific areas of the adult human brain. The reduction in PEP-19 immunoreactivity in Alzheimer's disease and Huntington's disease suggests that PEP-19 may play a role in the pathophysiology of these diseases through a mechanism of calcium/calmodulin disregulation. This may be especially apparent in Huntington's disease where the distribution of the product of the abnormal gene, huntingtin, alone is not sufficient to explain the pattern of pathology. Abnormal huntingtin associates more strongly with calmodulin than does normal huntingtin (Bao et al., 1996, Proc. natn. Acad. Sci. U.S.A., 93, 5037–5042) suggesting a disruption of calmodulin-mediated intracellular mechanism(s), very likely involving PEP-19.

Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of thetish mutant rat

Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat.

Subcortical connections of normotopic and heterotopic neurons in sensory and motor cortices of the tish mutant rat

Orthograde and retrograde tracers were used to examine subcortical connections of neurons in the neurological mutant tish rat. This animal exhibits bilateral heterotopia similar to those observed in epileptic humans with subcortical band heterotopia. Terminal varicosities were labeled in the striatum, thalamus, brainstem, and spinal cord following injections of the anterograde tracer biotinylated dextran amine (BDA) into the heterotopic cortex. The general topography of corticothalamic projections was evaluated by injecting the retrograde tracer Fluoro-Gold (FG) into ventral thalamic nuclei. Retrograde labeling of small-to-medium sized neurons was observed in layer VI of topographically restricted portions of the normotopic cortex. Similar appearing cells were labeled in the neighboring portions of the underlying heterotopia; however, these neurons did not display characteristic lamination or radial orientation. Thalamocortical terminals labeled by injecting BDA into the ventroposterolateral nucleus (VPL) were observed primarily in layer IV of the medial aspect of the normotopic somatosensory cortex. In contrast, a radial column of terminals was present in the underlying heterotopia. Typical barrel labeling was found in the lateral aspect of the normotopic somatosensory cortex after injecting the ventroposteromedial nucleus (VPM), whereas more diffuse patches of labeling were observed in the underlying heterotopia. Heterotopic neurons in the tish cortex, thus, exhibit characteristic features of subcortical connectivity. Both normotopic and heterotopic neurons in the tish brain project to appropriate subcortical sites and establish bidirectional topographic connections with the thalamus. These results suggest that primary sensory-motor information is represented in a parallel manner in the normotopic and heterotopic cortices of the tish rat. J. Comp. Neurol. 395:29–42, 1998. © 1998 Wiley-Liss, Inc.

The Diencephalon and Pretectum of the White Sturgeon (Acipenser transmontanus): A Cytoarchitectonic Study

The cytoarchitecture of the diencephalon and pretectum of the white sturgeon, Acipenser transmontanus, was studied utilizing cresyl violet stained serial paraffin sections. The identified cell groups were assigned to the preoptic area, hypothalamus, thalamus and posterior tubercle, epithalamus, synencephalon and pretectum. The outlines of the diencephalic and pretectal nuclei were projected graphically onto a midsagittal section of the brain, thus providing a reconstruction of the relative positions of the major cell groups. This facilitated comparisons with the diencephalic and pretectal nuclei of other ray-finned fishes. Our cytoarchitectural analysis indicates that the diencephalon and pretectum of the white sturgeon is intermediate to that described for cladistians and neopterygians. The preoptic area in Acipenser is relatively conservative compared to other ray-finned fishes but lacks distinct subdivisions in the magnocellular periventricular preoptic nucleus and includes a unique migrated rostral accessory nucleus. The hypothalamic walls are rather thin, and due to the presence of extensive lateral and posterior recesses and the lack of migrated nuclei, they superficially resemble the condition seen in sharks. The dorsal and ventral thalamic nuclei do not exhibit much variation compared to other ray-finned fishes, except for the presence of a small lateral posterior thalamic nucleus, the absence of a distinct ventrolateral thalamic nucleus, and slight differences in the internal organization of the ventromedial thalamic nucleus. The posterior tubercle in Acipenser clearly comprises more migrated cell groups than that of Polypterus, however, these cell groups are considerably less well defined than in neopterygians. As in other nonteleost actinopterygians, the habenular nuclei are highly asymmetrical with the right side larger than the left side. The cytoarchitectonic complexity of the pretectum in Acipenser is intermediate to that observed in Polypterus and neopterygians in that a magnocellular component within the superficial pretectal nucleus is clearly present but cannot be delineated as a distinct magnocellular superficial pretectal nucleus. Also, the posterior pretectal nucleus which is absent in Polypterus but which has been identified as a small nucleus both in Lepisosteus and Amia is represented in Acipenser by a small group of scattered cells.

Differential Effects of Unilateral Lidocaine Infusion into the Globus Pallidus on Consolidation and Performance of Inhibitory Avoidance

The striatum is involved in memory consolidation; also involved in this process is one of its two major efferent targets, namely, the substantia nigra. It is not clear, however, if the other target, the globus pallidus, participates in storage and/or performance of learned information. To examine this problem, male Wistar rats were trained in an inhibitory avoidance task and tested for retention 24 h afterward. Independent groups were infused, unilaterally, with 2% lidocaine in the pallidus either 2 min after training or 2 min before testing. No disturbances of memory were detected with posttraining infusion, but a significant deficit in retention was observed as a consequence of pretest infusion. Infusion of isotonic saline into the globus pallidus, or of lidocaine before testing into the parietal cortex, after training into the ventral thalamic nucleus, and both before training and testing into this thalamic nucleus were without effect. Taken together, the data indicate that unilateral inactivation of the GP interferes with retrieval of information derived from inhibitory avoidance training, but not with the early stages of memory consolidation of this task, and other work indicates that the pallidus may be involved in a late phase of this process.

Regional alterations in neuronal activity in dystonic hamster brain determined by quantitative cytochrome oxidase histochemistry

The neural mechanisms underlying idiopathic dystonia are currently unknown. Genetic animal models, such as the dt s= hamster, a model of idiopathic paroxysmal dystonia, may be helpful to providing insights into the pathophysiology of this common movement disorder. Recent metabolic mapping studies in the hamster model, using 2-deoxyglucose autoradiography, demonstrated altered 2-deoxyglucose uptake in motor areas such as the striatum, ventral thalamic nuclei, red nucleus, and deep cerebellar nuclei, during dystonic attacks. Whereas the 2-deoxyglucose method is thought to reflect mainly acute alterations of synaptic activity, determination of cytochrome oxidase activity has been suggested as a method of choice to examine sustained baseline changes in neuronal activity. Therefore, in the present study quantitative cytochrome oxidase histochemistry was used to identify chronic regional alterations in the absence of dystonic attacks in mutant hamsters. For comparison with recent 2-deoxyglucose studies, cytochrome oxidase activity was also determined during a dystonic attack, which was induced by mild stress. Cytochrome oxidase was determined in 109 brain regions of dystonic hamsters and non-dystonic, age-matched control hamsters. In the absence of a dystonic attack, a tendency to decreased cytochrome oxidase activity was found in most brain regions, possibly due to retarded brain development in mutant hamsters. Significant decreases in cytochrome oxidase activity were found in motor areas and limbic structures, such as hippocampus, piriform cortex, fundus striatum, globus pallidus, substantia nigra pars reticulata, mediodorsal nucleus of the thalamus, ventral pallidum, and interpositus nucleus of the cerebellum. After induction of a dystonic attack, the trend of decreased cytochrome oxidase activity disappeared, except in globus pallidus and interpositus nucleus of the cerebellum. Although the significant alterations in cytochrome oxidase activity in the absence of a dystonic attack were moderate, the data are in line with previous findings in the mutant hamsters, indicating that dysfunctions of the basal ganglia and their output nuclei are involved in the dystonic condition. Altered neural activity in limbic structures, found in the absence of dystonic attacks in mutant hamsters, may contribute to the stress-susceptibility of the animals.

Human thalamic nucleus mediating taste and multiple other sensations related to ingestive behavior.

Until now, taste was the only primary sensory modality for which the human central nervous system pathways were unknown. We report sensations evoked by stimulation at microampere current levels in the region of the human thalamic nucleus (ventralis caudalis parvocellularis internis) corresponding to the monkey taste relay nucleus. Stimulation in this region during awake neurosurgical procedures evoked special visceral/somatic (taste/pungent smell), general visceral (fullness of a hollow viscus), as well as painful and nonpainful general somatic sensations. General somatic or visceral sensation was evoked by stimulation at 80% of sites where special visceral/somatic sensation was evoked. These results suggest that primate taste relay mediates multiple sensations in addition to taste.

Differential distribution of mRNAs encoding phosphatidylinositol transfer proteins alpha and beta in the central nervous system of the rat.

The expression of the alpha and beta isoforms of phosphatidylinositol transfer protein (PI-TP alpha and PI-TP beta) in the adult rat brain was examined by in situ hybridization analysis with isoform-specific RNA probes. PI-TP alpha mRNA was detected in rather restricted regions of the brain whereas PI-TP beta mRNA was widely distributed in the brain. PI-TP alpha mRNA signals were remarkable in neocortex layers II/III and V/VI, Purkinje cell layer, deep cerebellar nuclei of the cerebellum, red nucleus and most part of brain stem. Low levels of PI-TP alpha transcript were present in CA3 of the hippocampus, ventral and dorsal thalamic nuclei, and motoneurons of spinal cord. No hybridization signals was obtained in the olfactory bulb, basal ganglia, amygdala, hypothalamus, and pituitary gland. In contrast, strong signals of PI-TP beta mRNA were detected in the dentate gyrus. The beta isoform mRNA was moderately expressed in olfactory bulb, layers II/III of the neocortex, striatum, CA1-CA4 regions of the hippocampus, medial habenula, cerebellum, amygdala, hypothalamus, spinal cord, and pituitary gland. Thalamus and brain stem contained relatively low, but significant levels of PI-TP beta transcript. The distinct distribution of PI-TP alpha and PI-TP beta mRNAs suggests different functional roles for each of the gene products in the mature nervous system.

Estradiol-17 beta increases serotonin transporter (SERT) mRNA levels and the density of SERT-binding sites in female rat brain.

The aim of the present study was to determine the effect of estradiol-17 beta (E2), in its positive feedback mode for gonadotropin release, on the serotonin transporter (SERT) in female rat brain. Levels of SERT mRNA were determined by in situ hybridization and SERT-binding sites were measured by quantitative [3H]paroxetine receptor autoradiography. The injection of estradiol benzoate (EB) in acutely ovariectomized rats increased significantly (approximately 50%) the numbers of cells that expressed SERT mRNA in the dorsal raphe nucleus and the density of SERT-binding sites in lateral septum (90%), basolateral amygdala (20%), ventral nucleus of thalamus (250%) and ventromedial hypothalamic nucleus (250%). SERT-binding sites in EB-treated rats were significantly lower in periaqueductal central grey (15%). These findings indicate that effects on SERT gene expression may be involved in the E2-induction of the gonadotropin surge. Together with our previous findings, they also suggest that the sex differences in depression and the apparent psychotropic effect of E2 may be due to the action of E2 on the serotonin transporter as well as 5-HT2A receptors.

Collateral projections from single neurons in the dorsal column nuclei to the inferior colliculus and the ventrobasal thalamus: a retrograde double-labeling study in the rat

A number of single neurons in the dorsal column nuclei (DCN) and the sensory trigeminal nuclear complex were found to project to the thalamus and the inferior colliculus (IC). In the rats which were injected unilaterally with tetramethylrhodamine-dextran amine (TMR-DA) and Fluoro-Gold (FG) respectively into the posterolateral ventral thalamic nucleus and the external nucleus of IC, a number of neuronal cell bodies labeled retrogradely with both TMR-DA and FG were found throughout DCN contralateral to the injections. A few double-labeled neurons were also seen in the caudomedial part of the gracile nucleus ipsilateral to the injections. The double-labeled DCN neurons had relatively small cell bodies which are oval or fusiform in shape. When the injection sites in the thalamus extend into the posteromedial ventral thalamic nucleus, a few double-labeled neuronal cell bodies were seen contralaterally in the trigeminal sensory nuclear complex, mainly in the caudal part of the interpolar spinal trigeminal nucleus.