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PubMed2006

The thalamus and midbrain in Reye syndrome.

A previously healthy 5 1/2-year-old male had Reye syndrome. He presented in coma with apnea 1 week after a viral infection and following 2 days of vomiting and progressive obtundation. He was in coma with dystonic posturing and intact brainstem function. Laboratory evaluation revealed initial hypoglycemia, and markedly elevated liver enzymes, prolonged clotting times, and elevated ammonia levels. No underlying metabolic disorder was present, and the patient completely recovered. On a modified diffusion-weighted image magnetic resonance imaging scan, restriction of diffusion in the thalamus and midbrain was observed. While abnormalities of the thalamus and midbrain have previously been reported, this is the first report of diffusion-weighted imaging indicating early impairment of water diffusion, a finding more commonly observed with stroke.

Child, Preschool↗

PubMed2004

Correlations between MRI-assessed volumes of the thalamus and cortical Brodmann's areas in schizophrenia.

BACKGROUND: We compared the thalamic-cortical volumetric correlational patterns in patients with schizophrenia and normal comparison subjects, and evaluated their relations to outcome. METHODS: High-resolution MR images were acquired in patients with schizophrenia (n=106) and normal comparison subjects (n=42). Patients were divided into good-outcome (n=52) and poor-outcome (Kraepelinian, n=54) subtypes based on their ability for self-care. Correlations between the relative gray and white matter volumes of the individual cortical Brodmann's areas and five dorsoventral levels of the thalamus were assessed. RESULTS: Compared to normal subjects, schizophrenia patients lacked significant thalamic gray matter volume correlations with the prefrontal and medial temporal cortical regions in the right hemisphere, and with frontal, cingulate, posterior parietal and occipital regions in the left hemisphere, while normal white matter volume cortical-thalamic correlations along the cingulate gyrus and in the temporal lobe were not found in schizophrenia patients in both hemispheres. In contrast to both normal comparison subjects and good-outcome group, schizophrenia patients with poor outcomes showed significant bilateral gray matter volume correlations between the dorsal thalamus and ventral prefrontal cortex, while the group differences in the white matter volume correlations were mostly restricted to the cingulate arch. CONCLUSIONS: Whereas patients with schizophrenia exhibit deficiencies in cortical-thalamic correlational patterns, poor outcome is associated with abnormal interregional correlations not observed in either normal subjects or patients with good outcomes. This latter finding may be explained by a core neurodevelopmental disturbance that results in aberrant cortical-thalamic connectivity in poor-outcome schizophrenia.

Adult↗

PubMed2005

Increased expression of glutaminase and glutamine synthetase mRNA in the thalamus in schizophrenia.

Numerous molecules enable the handling of glutamate that is destined for neurotransmitter release, including transporters, receptors and glutamatergic enzymes. Previous work in our lab has shown altered levels of transcript expression of excitatory amino acid transporters and a vesicular glutamate transporter in the thalamus in schizophrenia. These changes suggest that molecules that facilitate the release and reuptake of glutamate may be abnormal in schizophrenia. In this study we determined the levels of expression of phosphate activated glutaminase (PAG), which converts glutamine to glutamate, and glutamine synthetase (GS), which converts glutamate to glutamine, with the hypothesis that thalamic PAG and GS transcript expression is altered in schizophrenia. We investigated expression of PAG and GS mRNA using in situ hybridization in six different thalamic nuclei (anterior, dorsomedial, centromedial, ventral anterior, ventral and reticular) from 13 persons with schizophrenia and 8 comparison subjects and found that transcripts for PAG and GS were significantly increased in schizophrenia. Increased PAG and GS transcripts suggest enhanced glutamatergic neurotransmission in the thalamus and its efferent targets in schizophrenia.

Aged↗

PubMed2004

Interneurons and triadic circuitry of the thalamus.

The thalamus is strategically placed to control the flow of information to cortex and thus conscious perception. A key player in this control is a local GABAergic interneuron that inhibits relay cells. This interneuron is especially interesting because, in addition to a conventional axonal output, most of its output is via distal dendrites. The latter seem to be electrotonically and thus functionally isolated from the soma and axon, and they enter into complex synaptic arrangements. It is proposed that, because of special synaptic properties of its dendritic outputs, this local GABAergic interneuron of the thalamus provides gain control for the relay cell and thereby keeps relay of information to cortex within a fairly linear regime.

Animals↗

PubMed2006

An argument for an olfactory thalamus.

The mammalian olfactory system is unique in that sensory receptors synapse directly into the olfactory bulb of the forebrain without the thalamic relay that is common to all other sensory pathways. We argue that the olfactory bulb has an equivalent role to the thalamus, because the two regions have very similar structures and functions. Both the thalamus and the olfactory bulb are the final stage in sensory processing before reaching target cortical regions, at which there is a massive increase in neuron and synapse numbers. Thus, both structures act as a bottleneck that is a target for various modulatory inputs, and this arrangement enables efficient control of information flow before cortical processing occurs.

Animals↗

PubMed1999

Neurochemical adaptation to cocaine abuse: reduction of N-acetyl aspartate in thalamus of human cocaine abusers.

BACKGROUND: The aim of this study was to determine the existence of, and possible mechanisms for, chronic cocaine use-induced neurotoxicity in the human brain. Because in vivo magnetic resonance spectroscopy (MRS) provides a noninvasive way to detect biochemical and physiological changes in the brain, we sought to specifically determine the neurochemical adaptations in chronic cocaine-dependent subjects. METHODS: Twenty-one cocaine users and 13 non-drug-using, age-matched normal volunteers were recruited for an in vivo proton MRS study. Following screening that included physical examination, histories, and blood testing, cocaine group subjects received a spectral scan on a 1.5-T GE Signa scanner. Spectra were obtained from the left basal ganglia and/or the left thalamus from subjects in both groups using an rf bird-cage type head coil with single-voxel localization. RESULTS: The level of N-acetyl aspartate in the region of left thalamus was lower (17%) in the chronic cocaine user group but not in the region of left basal ganglia, compared with the control group. CONCLUSIONS: These results suggest that chronic cocaine use may induce abnormal neurochemical activity and a state of neuronal dysregulation and/or neurotoxicity. It will now be important to determine if these alterations are reversible during withdrawal and what the functional implications of this observation are with respect to cognitive function and drug relapse.

Adult↗

PubMed2000

Bilateral lesions of the gustatory thalamus disrupt morphine- but not LiCl-induced intake suppression in rats: evidence against the conditioned taste aversion hypothesis.

Rats decrease intake of a saccharin conditioned stimulus (CS) when followed by: (1) the administration of an aversive agent such as lithium chloride (referred to as a conditioned taste aversion, CTA); (2) access to a very palatable concentration of sucrose (referred to as an anticipatory contrast effect, ACE); or (3) the administration of a drug of abuse. It is not clear, however, whether the suppressive effects of drugs of abuse are mediated by their aversive or rewarding properties. The present set of experiments addressed this issue by examining the suppressive effects of morphine in rats with a lesion thought to dissociate the two phenomena (i.e., CTA and ACE). The results show that bilateral ibotenic acid lesions of the gustatory thalamus eliminate the suppressive effects of morphine, but fail to disrupt the suppressive effects of the aversive agent, lithium chloride. This pattern of results argues against the CTA account in favor of the reward comparison hypothesis. Specifically, the data suggest that rats suppress intake of a saccharin CS in anticipation of the availability of a preferred drug of abuse and that the gustatory thalamus is essential for this type of reward comparison process.

Animals↗

PubMed2001

Orexin A-like immunoreactivity in the hypothalamus and thalamus of the Syrian hamster (Mesocricetus auratus) and Siberian hamster (Phodopus sungorus), with special reference to circadian structures.

The orexins are recently discovered neuropeptides that reportedly play a role in energy homeostasis, in addition to various other physiological processes. The synthesis of orexin A undergoes diurnal variation in certain areas of the brain, while the mutation of the orexin receptor 2 gene has been implicated in canine narcolepsy. Since the circadian pacemaker in the suprachiasmatic nucleus modulates the sleep/wake cycle, there is a putative role for orexins in the mammalian circadian system. In this study, immunohistochemical techniques were used to determine the distribution of orexin A in the structures of the hypothalamus and thalamus of Syrian and Siberian hamsters. In both species, the pattern of immunoreactivity was similar. Cells immunoreactive for orexin A were noted in the lateral hypothalamic area. Immunoreactive varicose orexin A fibres were found throughout the hypothalamus. The suprachiasmatic nucleus possessed little or no immunoreactive orexin A fibres in its core, but had fibres at its periphery. The thalamus of both species contained comparatively few immunoreactive fibres, which were mainly localised around the midline. The thalamic intergeniculate leaflet contained a plexus of immunoreactive orexin A fibres throughout its rostro-caudal extent. Three areas of the brainstem, the dorsal and median raphe nuclei and the locus coeruleus, were also investigated owing to their relevance to the circadian system and all were found to contain immunoreactive orexin A fibres. The presence of orexin A-immunoreactive fibres in the neural architecture of the mammalian circadian system suggests an important role for orexin A in circadian timekeeping processes.

Animals↗

PubMed1997

Parabrachial nucleus neurons providing axons to both the thalamus and the spinal cord in the rat.

After injecting Fluoro-gold (FG) and tetramethylrhodamine-dextran amine (TMR-DA), respectively, into the medial part of the ventrobasal thalamus and the upper segments of the cervical cord of the rat, a small number of neuronal cell bodies were double-labeled retrogradely with both FG and TMR-DA in the parabrachial nuclear complex (BPN) ipsilateral to the injection into the thalamus. The cell bodies double-labeled with FG/TMR-DA were seen mainly in the Kölliker-Fuse subnucleus and additionally in the external medial subnucleus.

Animals↗

PubMed1998

Visceral afferent pathways to the thalamus and olfactory tubercle: behavioral implications.

The goal of this study was to support the hypothesis that visceral signals may integrate and influence behavior by way of direct pathways from the nucleus tractus solitarii (NTS) to the olfactory tubercle and the midline/intralaminar thalamus. An anterograde tracer, biotinylated dextran amine (BDA) was iontophoresed bilaterally into the caudal NTS to optimize terminal labeling. NTS-cortical projections traversed both limbs of the diagonal bands providing heavy innervation, and terminated lightly within layer 3 of the olfactory tubercle. NTS-thalamic projections terminated within anterior and, as previously shown, posterior divisions of nucleus paraventricularis thalami and avoided the adjoining mediodorsal thalamic nucleus. Heretofore unrecognized projections were traced to the parafascicular and reuniens thalamic nuclei, and the peripeduncular nucleus. Control experiments identified the nucleus gracilis as the principal source of ascending projections to ventroposterior lateral, posterior and intralaminar thalamic nuclei. Our data corroborate the supposition that olfactory signals may integrate with visceral stimuli in the striatal compartment of olfactory tubercle. NTS projections encompass thalamic nuclei that project topographically to the prefrontal cortex, hippocampus and ventral (limbic) striatum, regions activated by visceral stimulation. Structural data support the idea that compartments of the non-discriminative thalamus may contribute to perception and behavioral responses to visceral stimulation.

Afferent Pathways↗

PubMed2000

Differential distribution of metabotropic glutamate receptor subtype mRNAs in the thalamus of the rat.

L-Glutamate (L-Glu) is present in most excitatory synapses of the mammalian brain, acting on several receptor subtypes. Height different genes encoding metabotropic glutamate receptors (mGluRs) subtypes have been described (mGluR1-8), having a distinct distribution in the brain. In the present study, the distribution of mGluR1, 3, 4, 5 and 7 mRNAs was determined in 20 thalamic nuclei of adult rats by performing in situ hybridisation with subtype-specific 35S-labelled oligonucleotide probes. High expression of mGluR1 mRNA mainly occurred in midline nuclei such as the centromedial/centrolateral (CM/CL) nuclei, parafascicular and submedius nuclei, and in the ventroposteromedial (VPM) and posterior (Po) nuclei. In contrast, mGluR5 mRNA was more uniformly distributed at weak to moderate levels, except in the reuniens nucleus where a strong signal was detected. The mGluR3 mRNA was highly expressed in the reticular thalamic nucleus and almost not detectable in any other thalamic region. Additionally, mGluR3 mRNA was found not only in neurones but also in putative glial cells. The mGluR4 mRNA was abundant in most thalamic nuclei, with prominent expression in the CM/CL, Po and ventrobasal complex (VPM and ventroposterolateral, VPL). Finally, mGluR7 transcripts were found evenly distributed throughout the thalamus at moderate levels, the highest signal being detected in the paraventricular thalamic nucleus, VPM, VPL and Po. This differential distribution of mGluR subtypes in the rat thalamus may contribute to the heterogeneity of glutamate effects on thalamic neurones. The mGluR1, mGluR4 and mGluR7 receptors may be involved in the processing of somatosensory information because they are expressed in nuclei that receive direct sensory input.

Animals↗

PubMed1996

Functional characterisation of alpha 1-adrenoceptor subtypes mediating noradrenaline-induced inositol phosphate formation in rat thalamus slices.

In cross-chopped slices from rat thalamus and in the presence of 10 mM LiCl, noradrenaline stimulated the accumulation of [3H]inositol phosphates with [3H]inositol monophosphates ([3H]IP1) being the major product detected (86 +/- 2% of total [3H]inositol phosphates). Noradrenaline-induced [3H]IP1 accumulation was concentration-dependent and yielded and EC50 of 4.6 +/- 0.2 microM, maximum effect of 272 +/- 3% of basal formation and Hill coefficient (nH) of 1.6 +/- 0.1. The effect of 100 microM noradrenaline was inhibited by the alpha 1-adrenoceptor antagonists prazosin, (+)-niguldipine, 5-methylurapidil and WB-4101 (2-(2,6-dimethoxyphenoxyethyl) aminomethyl-1,4-benzodioxane). The inhibition curve for prazosin best fit to a single-site model whereas curves for (+)-niguldipine, 5-methylurapidil and WB-4101 best fit to a two-site model. The putative alpha 1D-adrenoceptor-selective antagonist BMY 7378 (8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8- azaspiro[4.5]decane-7,9-dione) showed low potency and efficacy to inhibit the response to noradrenaline. Pre-treatment of the slices with chloroethylclonidine (100 microM; 30 min) decreased by 64 +/- 4% the maximum response. Noradrenaline-induced [3H]IP1 accumulation was significantly reduced by Ca2+ removal (by 64 +/- 2%) and by the Ca(2+)-channel blockers Ni2+, Co2+ and nimodipine (inhibition of 56 +/- 6%, 54 +/- 5% and 41 +/- 5%, respectively). Taken together these results indicate that noradrenaline-induced inositol phosphate formation in thalamus slices is mainly mediated by the activation of both alpha 1B and alpha 1A subtypes of alpha 1-adrenoceptors.

Adrenergic alpha-Agonists↗

PubMed2002

Strategic infarcts of the thalamus in vascular dementia.

Strategic infarcts or focal hemorrhages involving the paramedian nuclei of the thalamus may alter consciousness and produce complex neuropsychological symptoms such as impairment of memory, attention and motivation. Lesions disrupting the thalamo-prefrontal circuits lead to severe subcortical dementia. We analysed here the clinical, neuropsychological and neuroimaging data of 19 patients with cerebrovascular lesions in the thalamus. In six patients with bilateral paramedian infarcts, and in two with anterior thalamic infarcts, vascular dementia and severe personality changes developed. SPECT findings did not correlate with the neuropsychological symptoms. Transcortical sensory and motor aphasia was observed in four patients with thalamic hemorrhages and infarcts. In these patients SPECT detected hypoperfusion in adjacent cortical areas. Clinical symptoms and outcome of four patients are reported in detail. The clinico-morphological correlations of the thalamo-cortical circuits are reviewed and the possible causes of multiple cognitive and behavioural consequences of vascular thalamic lesions are discussed.

Adult↗

PubMed1999

Evaluation of agonists and antagonists acting at Group I metabotropic glutamate receptors in the thalamus in vivo.

Recordings were made from single neurones in the ventrobasal thalamus of anaesthetised rats in order to evaluate the properties of several agonists and antagonists of Group I mGlu receptors. The selective mGlu1 receptor antagonist LY367385 was found to reduce excitatory responses to iontophoretically applied ACPD and DHPG whereas the mGlu5 agonist CHPG was resistant to antagonism. The antagonists LY367366 and LY393053 reduced responses to all three agonists, but without reducing responses to NMDA or AMPA. Although AIDA was also found to reduce mGlu agonist-evoked responses, this antagonist also produced significant reductions in responses to NMDA and AMPA. These data suggest that there are functional mGlu1 and mGlu5 receptors in the thalamus. Furthermore, LY367385 is a useful tool for investigating mGlu1 functions whereas LY367366 and LY393053 have a broader spectrum of action. The usefulness of AIDA as an antagonist in physiological experiments would appear to be limited by its effects against NMDA and AMPA.

Animals↗

PubMed1999

Pertussis toxin decreases absence seizures and GABA(B) receptor binding in thalamus of a genetically prone rat (GAERS).

Postsynaptic GABA(B) receptor-mediated events have previously been shown to be reduced by prior treatment with pertussis toxin in rat brain. In the present study genetic absence epilepsy rats from Strasbourg (GAERS) were given single bilateral injections of pertussis toxin (PTx 0.4 microg), denatured-PTx or vehicle saline into the relay nuclei of the thalamus under anaesthesia. After recovery the spike and wave discharge duration (SWD) was monitored for up to 6 days following which the brains were removed and GABA(B) or GABA(A) receptor autoradiography performed on 10 microm transverse sections. By 6 days the SWD of the rats treated with PTx was suppressed by 96% compared with vehicle-injected rats with a significant (62%) reduction even after 1 day. Denatured toxin had no effect at any time. After 6 days GABA(B), but not GABA(A), receptor binding was significantly reduced by 70-80% in the ventrolateral and ventral posteriolateral thalamic nuclei. No changes in other brain regions were detected and denatured toxin failed to alter GABA(A) or GABA(B) receptor binding in any brain region. These data implicate G-protein mechanisms in the generation of SWD in GAERS and support the role of GABA(B) receptors in their induction within the thalamus.

Animals↗

PubMed1999

Corticofugal modulation of functional connectivity within the auditory thalamus of rat, guinea pig and cat revealed by cooling deactivation.

Microelectrode recordings were simultaneously performed at multiple sites in the medial geniculate body (MGB) of anesthetized cats, rats and guinea pigs. We studied the effect of cortical deactivation on the association of neural activity within the thalamus during spontaneous activity. The corticofugal influence was suppressed by temporary cooling of the auditory cortex. Pairs of spike trains recorded from the same electrode were distinguished from cases where units were in MGB but recorded with different electrodes. Time domain analyses included crosscorrelations and search for precise repetition of complex spatiotemporal firing patterns of reverberating thalamic circuits. As a complementary approach we performed bispectral analyses of simultaneously recorded local field potentials in order to uncover the frequency components of their power spectra which are non linearly coupled. All results suggest that new functional neuronal circuits might appear at the thalamic level in the absence of input from the cortex. The newly active intrathalamic connections would provide the necessary input to sustain the reverberating activity of thalamic cell assemblies and generate low frequency non-linear interactions. The dynamic control exerted by the cortex over the functional segregation of information processing carried out in the thalamus conforms with theoretical neural network studies and with the functional selectivity-adaptive filtering theory of thalamic neuronal assemblies. Although this general conclusion remains valid across species, specific differences are discussed in the frame of known differences of the microcircuitry elements.

Animals↗

PubMed2003

Transient expression of S-100beta immunostaining in developing thalamus and somatosensory cortex of rat.

Serotonin is thought to affect the development of barrel fields in somatosensory cortex of rat and transient expression of the serotonin transporter has been reported in relevant thalamic (ventral posterior) and cortical (layer IV of parietal) regions in support of this. Much of the developmental role of serotonin is mediated by release of the neurotrophic protein S-100beta. The current work was thus undertaken to determine if S-100beta also shows a transient expression pattern in thalamus and barrel fields. Male Sprague-Dawley rats were examined immunocytochemically for S-100beta expression on postnatal days (PD) 1, 7, 15 and 22. Expression of S-100beta selectively peaked in the ventral posterior nucleus of the thalamus at PD 7, and in layer IV of the parietal cortex from PD 7 to 15, in a 'barrel-like' pattern. Our findings suggest that S-100beta could indeed be the mediator of serotonin's effects on barrel field formation.

Animals↗

PubMed1997

Innervation of the caudate nucleus, thalamus and red nucleus by the remaining sensorimotor cortex in cats with fetal or neonatal unilateral frontal cortex removal.

We studied the projections to the caudate nuclei, thalami and red nuclei from the remaining sensorimotor cortex in adult cats that had sustained a unilateral frontal cortex resection prenatally or neonatally. Four cats had the lesion at age E 50-55 and six animals sustained the ablation at age P 8-14 (seven cats were intact controls). All cats grew to young adulthood and then received injections of tritiated leucine-proline in the remaining sensorimotor cortex. Injection sites and axon terminal fields were reconstructed using autoradiography-processed tissue. In all cats the label filled a similar extent of the right pericruciate cortex. Terminal field densities in the subcortical nuclei were estimated using computer-based video software. Three medial-lateral sectors at five coronal levels were examined in the caudate nucleus. Three nuclear groups were analyzed in the thalamus (intralaminary, ventralis lateralis and ventrobasal complex). For the red nucleus, the four quadrants were examined at four coronal levels. The main goal of the study was to assess possible changes in the cortical innervation of the nuclei ipsilateral to the lesion. Therefore, the mean particle counts per nucleus (and per area or sector of nuclei) and per animal group were used to calculate percentage values for the decussated (crossed, or contralateral to the injection site) as a function of the non-decussated (uncrossed, or ipsilateral to the injection site) innervation. The percentage values for the crossed projections were: (a) for the entire caudate nucleus, 61.3% for the intact. 56.7% for the fetal-lesioned and 42.7% for the neonatal-lesioned cats, with no statistical differences between groups; (b) for the thalamus the proportion of crossed projections was minimal fluctuating between a low 0.06-0.16% for the nucleus ventralis lateralis and a high of 2.01-3.46% for the intralaminary nuclei, with the highest values belonging to the lesioned groups but with no significant differences between groups: (c) for the entire red nucleus, 1.98%, 12.74% (P < 0.05) and 6.76% for the intact, fetal- and neonatal-lesioned cats respectively. In the lesioned cats, the topography of the distribution of the axon terminals was bilaterally the same as in the controls. In conclusion, only the red nucleus of the frontal-lesioned cats showed an increased crossed innervation from the remaining sensorimotor cortex but this was relatively weak and statistically significant only for the fetal-lesioned animals. These results as well as the literature suggest that: (a) the crossed corticorubral projections in fetal cats may represent true reinnervation (i.e., newly originated, no preexisting terminals); (b) the relative paucity of the crossed projections in the present cats as compared to the extensive reorganization of subcortical terminals seen after cerebral hemispherectomy (our original postnatal lesion model) may be due to the much smaller size of the present cortical lesion which presumably induced only a limited amount of subcortical nuclear deafferentation.

Animals↗