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Lack of regional specificity for connections formed between thalamus and cortex in coculture.

The mammalian cerebral cortex consists of many structurally and functionally specialized areas, with characteristic input from particular nuclei of the thalamus. Some localized external influence, such as the arrival of fibres from the appropriate thalamic nucleus before or around the time of birth, could trigger the emergence of committed cortical fields from an undifferentiated 'protocortex. The guidance of axons from each thalamic nucleus to its appropriate target area in the cortex could, then, be crucial in the regulation of cortical differentiation. Recently, Yamamoto et al. and Bolz et al. have demonstrated that cocultured explants of rat lateral geniculate nucleus and visual cortex can form layer-specific interconnections. We have now tested the possibility that each cortical area exerts a selective trophic influence on axons from its appropriate thalamic nucleus, and vice versa, by coculturing explants of different regions of the thalamus and cortex taken at various stages of development. Although thalamo-cortical and cortico-thalamic connections formed in vitro can be remarkably normal in many respects, they lack regional specificity.

Animals↗

Non-invasive mapping of connections between human thalamus and cortex using diffusion imaging.

Evidence concerning anatomical connectivities in the human brain is sparse and based largely on limited post-mortem observations. Diffusion tensor imaging has previously been used to define large white-matter tracts in the living human brain, but this technique has had limited success in tracing pathways into gray matter. Here we identified specific connections between human thalamus and cortex using a novel probabilistic tractography algorithm with diffusion imaging data. Classification of thalamic gray matter based on cortical connectivity patterns revealed distinct subregions whose locations correspond to nuclei described previously in histological studies. The connections that we found between thalamus and cortex were similar to those reported for non-human primates and were reproducible between individuals. Our results provide the first quantitative demonstration of reliable inference of anatomical connectivity between human gray matter structures using diffusion data and the first connectivity-based segmentation of gray matter.

Adult↗

Diffuse basal ganglia or thalamus hyperechogenicity in preterm infants.

OBJECTIVE: To determine the incidence and factors associated with diffuse basal ganglia or thalamus hyperechogenicity (BGTH) in preterm infants. STUDY DESIGN: (1) Review of serial neurosonograms among neonates with gestational age (GA) <34 weeks born at Weiler Hospital during a 21-month period; (2) Color Doppler flow imaging; (3) Case-control study using GA group-matched controls; and (4) Blind reading of CT scans or MRIs in patients with BGTH. RESULTS: Among 289 infants, 24 (8.3%) had diffuse BGTH. Color Doppler flow imaging was normal in nine patients. The incidence of diffuse BGTH was inversely related to GA (P<0.01). Logistic regression (n=96) showed that diffuse BGTH was significantly associated with requirement of high-frequency oscillation (HFO) (P=0.031), severe intraventricular hemorrhage (IVH) (P=0.004), hypotension requiring vasopressors (P=0.040), hypoglycemia (P=0.031) and male gender (P=0.014). Most patients with diffuse BGTH had normal basal ganglia and thalamus on CT/MRI, one had a hemorrhage, and one had an ischemic infarction. CONCLUSIONS: In our series, diffuse BGTH occurred in 8.3%, and was associated with factors similar to those previously reported. In contrast, several series have reported almost exclusively linear or punctuate hyperechoic foci, corresponding to hyperechogenicity of the lenticulostriate vessels. Our data provide further evidence to suggest that diffuse BGTH and hyperechogenicity of the lenticulostriate vessels are two different entities. Additional studies are required to determine the long-term significance of diffuse BGTH.

Basal Ganglia↗

Hyperperfusion in the lateral temporal cortex, the striatum and the thalamus during complex visual hallucinations: single photon emission computed tomography findings in patients with Charles Bonnet syndrome.

We report the findings of single photon emission computed tomography using 123I-IMP and magnetic resonance image studies of five patients with Charles Bonnet syndrome (CBS) while they were having visual hallucinations. All patients developed complex visual hallucinations after suffering from eye disease. The mean age at onset of CBS was 71.6 years. Single photon emission computed tomography studies in all patients disclosed hyperperfusion areas with some asymmetrical appearances in the lateral temporal cortex, striatum and thalamus. These results suggest that when elderly people suffer from eye disease, subsequent excessive cortical compensation in the lateral temporal cortex, striatum and thalamus may precipitate the development of visual hallucinations.

Aged↗

Decreased blood flow of the left thalamus during somnolent episodes in a case of recurrent hypersomnia.

A 24-year-old male with recurrent hypersomnia associated with decreased blood flow in the thalamus on single photon emission computed tomography (SPECT) is reported. In the hypersomnolent period, the decrease of blood flow in the left thalamus was revealed in the SPECT and slow waves appeared sporadically or sometimes as a burst on the electroencephalogram (EEG). In a phase of insomnia in the convalescent period there were almost no slow waves in the resting EEG but many slow waves appeared on hyperventilation EEG and the power spectrum at this hyperventilation resembled the power spectrum at the resting EEG in the hypersomnolent period. In the remission period there was no abnormal data in these testings.

Adult↗

Anatomical evidence for a mechanism of lateral inhibition in the rat thalamus.

The aim of this study was to determine whether or not thalamic reticular nucleus (Rt) neurons form synaptic connections with the thalamocortical (TC) neurons from which they receive synaptic contacts. Therefore, we examined, in adult rats, the relationships between single TC and Rt neurons, which had been marked simultaneously with an anterograde/retrograde tracer (biocytin or Neurobiotin), using the extracellular or juxtacellular technique. (i) From 30 successful extracellular microapplications of marker into the Rt, 22 gave retrogradely marked TC somatodendritic arbors at the fringe of or clear outside the anterogradely darkly stained Rt axon terminal fields. Following biocytin application into the thalamus, few cells were retrogradely stained in the Rt at the periphery of the anterogradely labelled axon terminal field. (ii) The juxtacellular filling of a single Rt cell was accompanied by the back-filling of a single TC neuron (n = 4 pairs), which presumably formed synaptic contacts with the former cell. The somatodendritic complex of the back-filled TC neuron was located outside the Rt cell's axonal arbor. These anatomical data provide clear evidence that Rt and thalamic neurons predominantly form between themselves open rather than closed loop connections. Because TC neurons make glutamatergic synapses onto Rt cells, which are GABAergic, and are the first elements synaptically activated by prethalamic afferents into the TC-Rt network, the present results strongly support the hypothesis that Rt neurons principally generate a mechanism of lateral inhibition in the thalamus.

Animals↗

Convergence of afferents from superior sagittal sinus and tooth pulp on cells in the thalamus of the cat.

We have previously shown convergence of craniovascular and tooth pulp afferents in the cervical spinal cord of cats. This study looked for similar convergence in the thalamus. Fifty-four thalamic cells with input from tooth pulp, superior sagittal sinus, or both, were identified. Twenty-nine cells with tooth pulp and superior sagittal sinus input were located in the ventrobasal complex of the intralaminar nuclei. Most of these 29 cells were also excited by cooling the contralateral tooth pulp, and 21 had receptive fields on the contralateral face or forelimb. Twenty cells excited by stimulation of superior sagittal sinus, and not tooth pulp, were found in several nuclei. The 5 cells excited by stimulation of tooth pulp, but not sagittal sinus, were restricted to the ventrobasal complex. The data confirm convergence from sagittal sinus, tooth pulp, and skin in the thalamus of anaesthetized cats.

Afferent Pathways↗

The endogenous lipid oleamide activates serotonin 5-HT7 neurons in mouse thalamus and hypothalamus.

Oleamide is an endogenous lipid that accumulates during sleep deprivation and has hypothermic effects when administered to rodents. The mechanisms for its activity remain unknown. Intraperitoneal injections of oleamide elicited dramatic increases in content of c-fos mRNA and Fos protein in distinct brain regions, including cingulate and somatosensory cortical areas and numerous nuclei of the thalamus and hypothalamus, indicating that there are explicit targets for its action. In the thalamus and hypothalamus a majority of neurons induced for c-fos expression also expressed the serotonin 5-HT7 receptor, an allosteric target for oleamide in in vitro studies. These data suggest that oleamide may act at 5-HT7 receptors to elicit alterations in transcription that result in some of its physiological effects.

Animals↗

Somatotopic organization and cortical projections of the ventrobasal complex of the flying fox: an "inverted" wing representation in the thalamus.

The present study investigates the somatotopic representation in the somatosensory thalamus of a megachiropteran bat. Using standard microelectrode mapping techniques, representational maps were generated for the ventrobasal (Vb) and posterior (Po) thalamic complexes of the Grey-headed flying fox. Anatomical tracing from neocortical injections provided additional data confirming the somatotopy found physiologically. A full representation of the body surface innervated by the trigeminal and spinal nerves was found. However, in contrast with other mammals, the representations of the forelimb and adjacent thoracic trunk within the thalamus were inverted. This means that the distal portions of the wing membrane and the tips of the digits were represented dorsally in Vb, and the thoracic trunk was represented ventrally. In Po the digit tips were represented in the ventral most portion and the thoracic trunk in the dorsal portion of the nucleus. These results are discussed in relation to similarities of megachiropteran somatosensory thalamic nuclei to those of other mammalian species and in relation to the formation of thalamic somatotopic maps and fiber sorting.

Animals↗

Nitric oxide synthase and interferon-gamma receptor immunoreactivities in relation to ascending spinal pathways to thalamus, hypothalamus, and the periaqueductal grey in the rat.

The retrograde tracer fluoro-gold was injected into the periaqueductal grey, thalamus or hypothalamus, and spinal cord sections were processed for neuronal nitric oxide synthase (nNOS) immunohistochemistry to investigate the relationships of nNOS immunoreactive, and spinomesencephalic, spinothalamic and spinohypothalamic projection neurones. In addition, in the lateral spinal nucleus the relationship between spinomesencephalic, -thalamic and -hypothalamic projection neurones, and nNOS and interferon-gamma receptor immunoreactive structures was investigated at the lumbar level. No single retrogradely labelled spinomesencephalic, -thalamic or -hypothalamic neurone showed nNOS immunoreactivity. In the lateral spinal nucleus, however, many fluoro-gold-labelled neurones were closely apposed by both nNOS and interferon-gamma receptor immunoreactive structures, especially prominent in the hypothalamic injection cases. This study gave no evidence for nNOS immunoreactivity in spinal neurones projecting to the periaqueductal grey, thalamus or hypothalamus, but suggests that in the lateral spinal nucleus such neurones are contacted by both nNOS- and interferon-gamma receptor-containing axon terminals.

Animals↗

Inhibition of subliminally primed responses is mediated by the caudate and thalamus: evidence from functional MRI and Huntington's disease.

Masked prime tasks have shown that sensory information that has not been consciously perceived can nevertheless trigger the preactivation of a motor response. Automatic inhibitory control processes prevent such response tendencies from interfering with behaviour. The present study investigated the possibility that these inhibitory control processes are mediated by a cortico-striatal-pallidal-thalamic pathway by using a masked prime task with Huntington's disease patients (Experiment 1) and with healthy volunteers in a functional MRI (fMRI) study (Experiment 2). In the masked prime task, clearly visible left- or right-pointing target arrows are preceded by briefly presented and subsequently masked prime arrows. Participants respond quickly with a left or right key-press to each target. Trials are either compatible (prime and target pointing in the same direction) or incompatible (prime and target pointing in different directions). Prior behavioural and electrophysiological results show that automatic inhibition of the initially primed response tendency is reflected in a 'negative compatibility effect' (faster reaction times for incompatible trials than for compatible trials), and is shown to consist of three distinct processes (prime activation, response inhibition and response conflict) occurring within 300 ms. Experiment 1 tested the hypothesis that lesions of the striatum would interrupt automatic inhibitory control by studying early-stage Huntington's disease patients. Findings supported the hypothesis: there was a bimodal distribution for patients, with one-third (choreic) showing disinhibition, manifested as an absent negative compatibility effect, and two-thirds (non-choreic) showing excessive inhibition, manifested as a significantly greater negative compatibility effect than that in controls. Experiment 2 used fMRI and a region of interest (ROI) template-based method to further test the hypothesis that structures of the striatal-pallidal-thalamic pathway mediate one or more of the processes of automatic inhibitory control. Neither prime activation nor response conflict significantly engaged any ROIs, but the response inhibition process led to significant modulation of both the caudate and thalamus. Taken together, these experiments indicate a causal role for the caudate nucleus and thalamus in automatic inhibitory motor control, and the results are consistent with performance of the task requiring both direct and indirect striatal-pallidal-thalamic pathways. The finding that Huntington's disease patients with greater chorea were disinhibited is consistent with the theory that chorea arises from selective degeneration of striatal projections to the lateral globus pallidus, while the exaggerated inhibitory effect for patients with little or no chorea may be due to additional degeneration of projections to the medial globus pallidus.

Adult↗

Magnetic resonance spectroscopy and imaging of the thalamus in idiopathic generalized epilepsy.

Experimental work in animal models of generalized epilepsy and clinical data in humans with idiopathic generalized epilepsy (IGE) indicate that the thalamo-cortical circuitry is involved in the generation of epileptic activity. The purpose of this study was to evaluate in vivo the chemical and structural integrity of the thalamus in patients with IGE. Thalamic proton magnetic resonance spectroscopic imaging (1H-MRSI), measuring N-acetylaspartate (NAA), choline-containing compounds and creatine (Cr) was performed in 20 IGE patients and in a group of age-matched healthy subjects. Additionally, 1H-MRSI measurements were taken in the insular cortex, the posterior temporal lobe white matter and the splenium of the corpus callosum. MRI volumetric analysis of the thalamus was performed in all patients. At the time of the examination, seizures were well controlled in 10 IGE patients and poorly controlled in nine. One patient was newly diagnosed and had the MRI and MRSI examination prior to starting the antiepileptic medication. In IGE patients, 1H-MRSI showed a reduction of mean thalamic NAA/Cr compared with normal controls; no difference was found in NAA/Cr in the other examined areas. There was no difference in NAA/Cr between patients whose seizures were well controlled and those in whom seizures were not controlled. There was no correlation between thalamic NAA/Cr and mean number of spike and wave complexes. We found a significant negative correlation between thalamic NAA/Cr and duration of epilepsy. The mean thalamic volume in patients with IGE was not different from normal controls. These results show evidence of progressive thalamic neuronal dysfunction in patients with IGE supporting the notion of abnormal thalamo-cortical circuitry as a substrate of seizure generation in this form of epilepsy. The thalamic dysfunction may occur regardless of amount of spike and wave activity.

Adult↗

Mental chronometry of target detection: human thalamus leads cortex.

Attentive monitoring of environmental stimuli is most fundamental for rapid target detection. The aim of this study was to assess the timing of thalamic versus cortical processes involved in this cognitive operation. To this end, simultaneous depth and scalp EEG was recorded in eight patients with essential tremor, undergoing thalamic deep brain stimulation (DBS), when the DBS electrodes could be accessed via their temporarily externalized leads. The patients performed an oddball task consisting of 300 presentations of one frequent and two rare visual cues, appearing in randomized order. One of the rare cues was defined as a target, the occurrences of which had to be indicated by a button press (motor condition) or silently counted (non-motor condition). At the scalp and the thalamus, event-related potentials (ERP) were largest upon target presentation, with peak latencies in the time domain of classical P300 responses. Remarkably, target-specific thalamic ERP emerged significantly prior to scalp P300. Furthermore, whereas scalp ERP had a higher amplitude upon rare than upon frequent non-target signals, thalamic ERP were independent of stimulus probability. This pattern was identified during motor and non-motor task execution. We conclude that the human thalamus specifically supports the early recognition of target events and can widely distribute this label through its divergent cortical projections.

Adult↗

Glutamatergic excitatory responses of anterior cingulate neurons to stimulation of the mediodorsal thalamus and their regulation by GABA: an in vivo iontophoretic study.

Anatomical and physiological studies in the rat have shown projections from the medial dorsal thalamus to the anterior cingulate cortex. We used multibarrel iontophoresis to identify the neurotransmitter used in this thalamic projection. Extracellular responses were recorded from 165 cingulate neurons in anesthetized rats after electrical stimulation of the medial dorsal thalamus and vicinity. Forty-four of these cells (27%) showed an excitatory response to thalamic stimulation. In a further 40 cells that showed no baseline excitation, iontophoresis of the GABAA antagonist bicuculline methiodide revealed excitatory responses. The GABAB antagonist CGP-35348 attenuated longer-latency inhibition in 5 of 10 cells. In 23 of 49 (47%) of the above cells, AMPA antagonist iontophoresis (either CNQX or DNQX) selectively decreased the excitatory response to thalamic stimulation. The NMDA antagonist 3[(R)-2-carboxypiperazin-4-yl]-propyl-1-phosphonic acid had no such effect. These data suggest that the thalamic projection to anterior cingulate cortex is glutamatergic, acting principally via AMPA receptors, and that the response of cingulate neurons to thalamic stimulation is regulated by GABA acting at both GABAA and GABAB receptors.

Animals↗

Oversized, auditory responsive units of rostral, mid, and posterolateral thalamus.

Activity was recorded from 343 units of rostral, mid, and posterolateral thalamus following a conditioned click stimulus (CS). Over 40% of units responded with increased discharge in cats conditioned to blink to the CS. Twenty-nine units with short latency (less than 40 ms) responses were injected intracellularly with phaseolus lectin and identified morphologically; 83% had long, thick primary dendrites with smaller secondary branches. Almost half (46%) had larger somata than the largest previously described thalamic neurons of this morphologic classification. The results suggest that a previously unidentified class of oversized cells is likely to contain many short latency, auditory responsive units. A substantial number of these cells (36%) projected extrathalamically into the internal capsule, and thus may constitute a new auditory pathway between thalamus and cortex.

Acoustic Stimulation↗

Fos expression in GHB-induced generalized absence epilepsy in the thalamus of the rat.

Using the model of gamma-hydroxybutyrate (GHB)-induced generalized absence epilepsy, the present work investigated the distribution of fos oncoprotein expression in the rat thalamus with fos antibody immunohistochemistry. Thirty minutes after absence-like seizures, some fos-immunoreactive cell nuclei were found in bilateral thalamic paraventricular nuclei (PV). After a further 30 min, a massive bilateral induction of fos was observed in the lateral habenular nucleus (LHb), the PV, the rhomboid thalamic nucleus, and the intralaminar nuclei of the thalamus. These results suggest that the LHb and the midline and intralaminar thalamic nuclei may very likely be involved in the pathophysiology of absence seizures.

Animals↗

Slow wave sleep is accompanied by release of certain amino acids in the thalamus of cats.

To determine whether EEG synchronization in sleep has a metabolic equivalent, we investigated state-dependent changes in extracellular concentrations of amino acids. In vivo microdialysis studies were performed in the ventroposterolateral (VPL) nuclei of the thalamus of cats during natural slow wave sleep (SWS), waking (W) and carbachol-induced paradoxical sleep (PS) like episodes. About two-fold increases in aspartate, glutamate, asparagine, glycine, alanine and gamma-aminobutyric acid (GABA) were observed in SWS compared with control samples collected in W, but serine increased to 487 +/- 211%. In the PS-like state, glutamine increased and GABA decreased. These results suggest changes in intracellular processes reflected by amino acid release in the thalamus, specific to slow wave generation in EEG during natural sleep.

Amino Acids↗

Distribution of GABA(B(1a)), GABA(B(1b)) and GABA(B2) receptor protein in cerebral cortex and thalamus of adult rats.

The distribution of GABA(B) receptor subunits GABA(B(1a)), GABA(B(1b)) and GABA(B2), has been examined in the cerebral cortex and thalamus of adult rats using an immunocytochemical technique. GABA(B(1a)) and GABA(B(1b)) subunits co-localized with GABA(B2) in the cortex, where afferent thalamic GABAergic axons project to pyramidal neurones. The expression patterns of GABA(B(1a)), GABA(B(1b)) and GABA(B2) were similar throughout the thalamus. The data suggest that the GABA(B(1b)) subunit might be the presynaptic isoform in the thalamo-cortical pathway with the GABA(B(1a)) subunit possibly present at postsynaptic sites on cell bodies. This contrasts with our previous data, obtained in cerebellum and spinal cord which indicate opposite locations. Thus, it seems unlikely that functional role along with cellular location can be assigned in a general manner to specific GABA(B) receptor subunit splice variants.

Age Factors↗