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Long-term effects of alloxan-induced diabetes on the nucleus ventralis posterolateralis in the thalamus of the rat.

The present paper describes the long-term ultrastructural changes in the nucleus ventralis posterolateralis of the thalamus of male Wistar rats after alloxan-induced diabetes. Degenerating dendrites were characterized by an electron-dense cytoplasm with scattered endoplasmic reticulum and ribosomes. Degenerating axon terminals were characterized by an electron-dense cytoplasm and clustering of small spherical agranular vesicles. Degenerating axon terminals formed axosomatic synapses with seemingly normal cell bodies and axodendritic synapses with normal as well as degenerating dendrites. Degenerating axons (both myelinated and unmyelinated) were readily encountered in the neuropil. Activated microglial and astrocytic cells in the neuropil were in the process of phagocytosis or had residua in their cytoplasm.

Animals↗

Metabolic disconnection between the mediodorsal nucleus of the thalamus and cortical Brodmann's areas of the left hemisphere in schizophrenia.

OBJECTIVE: The authors' goal was to examine interregional correlations of thalamocortical metabolic activity during a verbal learning task in schizophrenia. METHOD: They used [18F]fluorodeoxyglucose positron emission tomography in 41 unmedicated patients with schizophrenia and 59 normal comparison subjects. RESULTS: A metabolic disconnection was observed in patients with schizophrenia in the left hemisphere between the mediodorsal nucleus and widespread frontotemporal cortical regions, and stronger-than-normal intercorrelations were found between the pulvinar and superior temporal, selected parietal, posterior cingulate, and occipital areas. CONCLUSIONS: Deficits in the functional interrelationships between the left frontotemporal cortices and the left mediodorsal nucleus of the thalamus complement inferences from postmortem and magnetic resonance imaging volumetric studies identifying a thalamic diathesis in schizophrenia.

Adolescent↗

Circadian and photoperiodic time measurement in male Syrian hamsters following lesions of the melatonin-binding sites of the paraventricular thalamus.

Autoradiographic studies using [125I]iodomelatonin in several species, including the Syrian hamster, have revealed that the rostral region of the anterior paraventricular nucleus of the thalamus (aPVT) contains a very high density of binding sites for melatonin. In two studies, small or large bilateral electrolytic lesions of the aPVT were made in adult male hamsters maintained on long days (LD 16:8). The hamsters were then transferred to short days (LD 8:16) to test whether testicular regression could occur in response to a decrease in photoperiod. Serum prolactin concentrations were measured as a second photoperiodic response. All unoperated control hamsters showed the typical short-day photoperiodic response: A decrease in serum luteinizing hormone (LH) and prolactin concentrations and testicular regression all occurred within 6 weeks in short days, followed by the development of scotorefractoriness. Lesions of the aPVT did not significantly affect the rate or the degree of the short-day-induced decline in serum levels of LH or prolactin, nor the pattern of testicular regression and the subsequent expression of refractoriness. To enable us to determine whether the aPVT might be involved in the entrainment or the expression of circadian rhythms, locomotor activity was monitored continuously in lesioned and control groups in Experiment 2, prior to and following the switch to short days. The reduction in photoperiod (involving an 8-hr advance in the time of lights-off and an 8-hr extension of the dark phase) caused a decompression of the nocturnal activity bout of control animals, so that after 2 weeks in short days, activity onset had also advanced to regain its phase relationship to the timing of lights-off. A similar pattern of reentrainment was observed in lesioned animals, and no differences were observed between treatment groups in the rate of entrainment and decompression. In addition, both intact controls and animals bearing large bilateral lesions of the aPVT exhibited robust free-running circadian rhythms of locomotor activity when held under constant dim red light. In summary, the integrity of the aPVT is not necessary for the seasonal response of the reproductive axis and prolactin secretion to photoperiod, nor for photic entrainment of activity rhythms, in the Syrian hamster.

Animals↗

Corticosterone can act at the posterior paraventricular thalamus to inhibit hypothalamic-pituitary-adrenal activity in animals that habituate to repeated stress.

Glucocorticoids released by stress bind to glucocorticoid (GR) and/or mineralocorticoid receptors (MR) to exert negative feedback of subsequent hypothalamic-pituitary-adrenal (HPA) responses to stress. Feedback inhibition is implicated in habituation of HPA activity to repeated exposure to the same (homotypic) stressor. We hypothesized that the posterior paraventricular thalamus (pPVTh) is a site where corticosterone acts to exert negative feedback during repeated stress and that is important for habituation. As previously reported, the pPVTh inhibits HPA responses to homotypic and heterotypic stressors in repeatedly, but not acutely, stressed rats. We conducted a series of experiments involving intra-pPVTh administration of MR and/or GR agonists or antagonists during different time frames over 8 d of restraint. MR exist in the pPVTh, as do GR as shown by our immunocytochemical results. Acute intra-pPVTh injection of MR and/or GR antagonist before the eighth restraint did not alter expression of habituation. Because habituation may develop before d 8, we manipulated GR and MR in the pPVTh throughout 8 d of stress using intra-pPVTh corticosterone implants, which enhanced habituation on d 8 without affecting acute stress responses. Conversely, daily intra-pPVTh injections of GR and MR antagonists on d 1-7 of restraint prevented habituation on d 8. These data suggest that corticosterone released during repeated stress can act at GR and MR in the pPVTh to inhibit HPA responses to homotypic stress. We also found that some GR-containing cells in the pPVTh project to the medial prefrontal cortex and basolateral amygdala, suggesting that pPVTh-induced inhibition of HPA activity is potentially mediated by its projections to these select limbic structures.

Adrenocorticotropic Hormone↗

A role for subplate neurons in the patterning of connections from thalamus to neocortex.

During cerebral cortical development, ingrowing axons from different thalamic nuclei select and invade their cortical targets. The selection of an appropriate target is first evident even before thalamic axons grow into the cortical plate: initially axons accumulate and wait below their cortical target area in a zone called the subplate. This zone also contains the first postmitotic neurons of the cerebral cortex, the subplate neurons. Here we have investigated whether subplate neurons are involved in the process of target selection by thalamic axons by ablating them from specific cortical regions at the onset of the waiting period and examining the subsequent thalamocortical axon projection patterns. Subplate neurons were ablated at the onset of the waiting period by intracortical injections of kainic acid. The effect of the ablation on the thalamocortical projection from visual thalamus was examined by DiI-labeling of the LGN days to weeks following the lesion. At two to four weeks post-lesion, times when LGN axons would have normally invaded the cortical plate, the axons remained below the cortical plate and grew past their appropriate cortical target in an anomalous pathway. Moreover, examination of LGN axons at one week post-lesion, a time when they would normally be waiting and branching within the visual subplate, indicated that the axons had already grown past their correct destination. These observations suggest that visual subplate neurons are involved in the process by which LGN axons select and subsequently grow into visual cortex. In contrast, subplate neurons do not appear to play a major role in the initial morphological development of the LGN itself. Subplate ablations did not alter dendritic growth or shapes of LGN projection neurons during the period under study, nor did it prevent the segregation of retinal ganglion cell axons into eye-specific layers. However, the overall size of the LGN was reduced, suggesting that there may be increased cell death of LGN neurons in the absence of subplate neurons. To examine whether subplate neurons beneath other neocortical areas play a similar role in the formation of thalamocortical connections, subplate neurons were deleted beneath auditory cortex at the onset of the waiting period for auditory thalamic axons. Subsequent DiI labeling revealed that in these animals the majority of MGN axons had grown past auditory cortex instead of innervating it. Taken together these observations underscore a general requirement for subplate neurons throughout neocortex in the process of cortical target selection and ingrowth by thalamic axons.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Pronounced cell death in the absence of NMDA receptors in the developing somatosensory thalamus.

Genetic deletion of NMDA glutamate receptors disrupts development of whisker-related neuronal patterns in the somatosensory system. Independent studies have shown that NMDA receptor antagonists increase cell death among developing neurons. Here, we report that a dramatic feature of the developing somatosensory system in newborn NMDA receptor 1 (NMDAR1) knock-out mice is increased cell death in the ventrobasal nucleus (VB) of the thalamus. Sections were subject to terminal deoxynucleotidyl transferase dUTP nick end labeling staining for apoptotic DNA fragmentation, thionine staining for pyknotic nuclei, silver staining for degenerating cells, and immunostaining for caspase-3. All four methods demonstrated that deletion of NMDAR1 causes a large (on the order of threefold to fivefold) increase in cell death in the VB. The NMDA receptor antagonists dizocilpine maleate (MK-801) and phencyclidine also increase cell death in this structure. The onset of increased cell death in the VB in the absence of NMDA receptor function is approximately the time of birth, overlaps with naturally occurring cell death and synaptogenesis, and displays some anatomical specificity. For example, there was no increase in cell death in the hippocampus or neocortex of NMDAR1 knock-out mice at any of the time points examined: embryonic day 15.5 (E15.5), E17.5, and postnatal day 0. We also report a significant reduction in the size of the VB that is evident starting at E17.5. The results indicate that NMDA receptors play a major role in cell survival during naturally occurring cell death in the VB and demonstrate that cell death is a consideration in NMDA receptor knock-out studies.

Animals↗

Large calcified cystic cavernous angioma in the thalamus--case report.

A 52-year-old female presented with an unusual large cystic cavernous angioma with dense calcification in the thalamus manifesting only as headache despite the large mass with surrounding brain edema. Both T1- and T2-weighted magnetic resonance images revealed a large cystic mass with an intramural nodule appearing a reticulated, irregular mixed intensity core. The lesion was totally removed through a transcortical-transventricular approach. The postoperative course was uneventful with no signs of neurological deficit or residual mass 5 years later.

Brain Neoplasms↗

Demands during maze. learning in limbic epileptic rats: selective damage in the thalamus?

A qualitatively evident enhancement of chromolytic neurons within the lateral posterior thalamus of rats in which limbic seizures had been induced by lithium and pilocarpine and who were later trained for spatial memory was assessed quantitatively. The significant increase in the numbers of chromolytic neurons and the decrease in the numbers of normal neurons for these rats compared to the reference brains suggested these morphological changes were recent. The hypothesis that excessive stimulation of the lateral posterior nucleus by daily training in a radial maze may have facilitated the necrosis was supported by the inverse relationship between a linear combination of the numbers of normal neurons and oligodendroglia and the rate of learning during the earlier but not the later sessions. An implication for iatrogenic effects from rehabilitation of humans following brain injury was suggested.

Animals↗

Firing modes and membrane properties in lemniscal auditory thalamus.

In neurons of the auditory thalamus, patterned sequences of action potentials encode the features of sound stimuli. The patterns vary with the membrane potential, characterizing states of wakefulness and sleep. We studied the dependence of the patterns on the membrane potential and specific voltage-gated conductances, using whole-cell patch-clamp recordings from neurons in the ventral medial geniculate body (MGBv) of in vitro slices. Thalamocortical neurons, identified with neurobiotin, exhibited different firing patterns to an excitatory input, depending on the initial membrane potential. From depolarized potentials, the neurons fired in a tonic mode. The delay to firing in this mode was regulated by a balance of persistent Na+ and A-type K+ conductances. When transiently depolarized from hyperpolarized holding potentials, the neurons fired brief phasic responses (burst mode). Phasic responses were induced by low threshold Ca2+ spikes (LTSs); the LTS-amplitude was controlled by Na+ and K+ conductances. Under favourable conditions, an LTS triggered more than one action potential and one or more high threshold Ca2+ spikes (HTSs). Consciously perceived sound signals are transmitted in the tonic mode. During sleep, alerting stimuli may interact with membrane non-linearities, converting hyperpolarized bursting MGBv neurons to the tonic mode.

Action Potentials↗

Behavioral steering in dual and social states of conation by the amygdala, hypothalamus, ventral striatum, and thalamus.

Conative information relating to goal states is proposed as regulating columnar information structures in the neocortex. These structures may handle a spatiotemporal hierarchy of sensorimotor information and conative information. In basic behavioral states, a subcortical system selects a dominant modality of conation (corresponding to a specific goal state) from cortical and subcortical sources, and enhances or suppresses activity in neocortical information structures, yielding the selected modality. These adjustments steer behavior relative to the goal state, allowing assembly of new behavior patterns. For opposing or cooperative modalities of conation, a dual-state system is proposed that modulates the basic-state system. For more extended combinations of conative modalities, a further function is needed that interrelates the basic-state system and the cortex to provide hierarchical conation. Basic-state system control may be exercised by the hypothalamus, influencing the cortex via the thalamus. Other conative control functions may be implemented by the amygdala and the ventral striatum. Opiatergic circuits may be involved in modifying conative components of information.

Amygdala↗

Ultrastructural analysis of the terminals of various somatosensory pathways in the ventrobasal complex of the rat thalamus: an electron-microscopic study using wheatgerm agglutinin conjugated to horseradish peroxidase as an axonal tracer.

We used wheatgerm agglutinin conjugated to horseradish peroxidase (WGA:HRP) as an anterograde tracer to label the terminals of the lemniscal, spinothalamic, and trigeminothalamic pathways in the ventrobasal complex of the rat thalamus (VB). The use of benzidine dihydrochloride (BDHC) as the chromogen allowed us to view the labeled profiles with the electron microscope and permitted us to compare the morphology of the terminals from the various pathways. We found that all the labeled somatosensory pathways terminate in the VB in the form of large terminals that contain round synaptic vesicles and make numerous asymmetrical synaptic contacts, usually with dendritic protrusions and proximal dendrites. The present results demonstrate that pathways conveying noxious and non-noxious somatosensory information terminate upon thalamic neurons with synaptic terminals having similar morphological features.

Afferent Pathways↗

Unilateral germinomas involving the basal ganglia and thalamus.

Clinical characteristics of six cases of germinoma involving a unilateral basal ganglion and thalamus are summarized. The incidence was estimated as 10% of all intracranial germinomas. The average age at the onset was 10.5 years. The sex incidence showed a male dominance. The clinical course was slowly progressive, and the average duration between onset and diagnosis was 2 years 5 months. Common symptoms and signs were hemiparesis in all cases, fever of unknown origin and eye symptoms in most, mental deterioration and psychiatric signs in three, and convulsions, pubertas praecox, and diabetes insipidus in two. Signs of increased intracranial pressure were found in only two cases in the later state of the disease. Early diagnosis is difficult because of nonspecific symptomatology and slow progression. Carotid angiography and pneumoencephalography showed abnormal findings compatible with basal ganglia and thalamic tumors, but not specific to germinoma. Ipsilateral cortical atrophy and ventricular dilatation might be significant findings. Radioisotope scanning was useful. Computerized tomography scans were the best method of detecting the location and nature of this tumor, and repeat scans showed response to radiation therapy.

Adolescent↗

Long-term evaluation of deep brain stimulation of the thalamus.

OBJECT: The effects of thalamic deep brain stimulation (DBS) on essential tremor (ET) and Parkinson disease (PD) have been well documented, but there is a paucity of long-term data. The aim of this study was to evaluate the long-term safety and efficacy of DBS of the ventralis intermedius nucleus (VIM) of the thalamus for PD and ET. METHODS: Thirty-eight of 45 patients enrolled at five sites completed a 5-year follow-up study. There were 26 patients with ET and 19 with PD undergoing 29 unilateral (18 ET/11 PD) and 16 bilateral (eight ET/eight PD) procedures. Patients with ET were evaluated using the Tremor Rating Scale, and patients with PD were evaluated using the Unified Parkinson's Disease Rating Scale. The mean age of patients with ET was 70.2 years and 66.3 years in patients with PD. Unilaterally implanted patients with ET had a 75% improvement of the targeted hand tremor; those with bilateral implants had a 65% improvement in the left hand and 86% in the right compared with baseline. Parkinsonian patients with unilateral implants had an 85% improvement in the targeted hand tremor and those with bilateral implants had a 100% improvement in the left hand and 90% improvement in the right. Common DBS-related adverse events in patients receiving unilateral implants were paresthesia (45%) and pain (41%), and in patients receiving implants bilaterally dysarthria (75%) and balance difficulties (56%) occurred. Device-related surgical revisions other than IPG replacements occurred in 12 (27%) of the 45 patients. CONCLUSIONS: Thalamic stimulation is safe and effective for the long-term management of essential and Parkinsonian tremors. Bilateral stimulation can cause dysarthria and incoordination and should be used cautiously.

Activities of Daily Living↗

[Familial fatal insomnia: a human prion disease which opens the door to a greater understanding of the thalamus].

In 1986, Lugaresi [1] described fatal familial insomnia (FFI), an inherited prion disease, characterised by untreatable insomnia and dysautonomia. The most severe neuropathological changes have been found in the mediodorsal (MD) and anterior (A) thalamic nuclei. The data lead to think that the thalamus could play an important role in the wake-sleep cycle and other vegetative and endocrine circadian activities, specially MD and A.

Adult↗

Unequal representation of the temporal and nasal retina in an anomalous projection to the lateral thalamus.

Study of an anomalously regenerated, nontopographically organized retinal projection in the frog olfactory cortex revealed that the temporal retina is the main source of this projection, suggesting the existence of specific temporal fiber-directed attractant or trophic influences. In the present study, we examined the organization of an anomalous retinal projection that forms in the frog thalamus after ablation of the optic tectum. The projections from different sectors of the retina were studied by means of the anterograde transport of biotinylated dextran-amine (BDA) delivered to incisions made across the nerve fiber layer in frogs surviving ablation of the contralateral tectal hemisphere for 13-46 weeks. The projections from nasal retinal sectors were always lightly constructed in the aberrant terminal field, whereas their projections to the lateral geniculate complex remained reasonably strong. In contrast, the projections from temporal retinal sectors, though also weak initially, in time became robust and filled the aberrant field over most of its extent. The specific amplification of the temporal fiber projection now observed in two foreign targets provides further evidence for the existence of target-based, attractant/trophic molecules with functional specificity for temporal retinal fibers. That such agents can exist or be inducible in a foreign area would suggest that they belong to a family of molecules having natural biological activity in normal development or regeneration. However, the possibility that the augmented role of the temporal retina in these projections is a result of experience-based plasticity is also discussed.

Animals↗

Evoked responses of the anterior cingulate cortex to stimulation of the medial thalamus.

In the present study we characterized the field potentials in the anterior cingulate cortex (ACC) evoked by electrical stimulation of the medial thalamus (MT), and elucidated the synaptic organization of the ACC. Male Sprague Dawley rats were maintained in general anesthesia by alpha-chloralose (50 mg/kg, i.v.). Tungsten micro-electrodes were used for electric stimulation and recordings. The field potentials and multiple unit activities in the ACC were evoked by electric stimulation of the MT where the nociceptive responses were identified. A MT-evoked positive-negative potential was recorded on the medial frontal surface. The polarity of the surface negative potential was reversed between 0.5 to 1.0 mm in the deep layer of the ACC. Maximum evoked negative potential appeared at about 4 mm anterior to the bregma and 1 mm lateral to the midline. The maximum evoked positive potential occurred at about 3 mm anterior to the bregma and 1 mm lateral to the midline. The evoked multiple unit activities coincided with the deep negative field potential at a latency between 16 ms and 24 ms at a depth between 0.5 mm and 1.5 mm in the ACC. These electrophysiological findings confirmed that nociceptive information in the MT is transmitted to the ACC and trans-synaptically activates deeper and more superficial layers of cortical neurons.

Afferent Pathways↗

Status epilepticus causes necrotic damage in the mediodorsal nucleus of the thalamus in immature rats.

Status epilepticus (StE) in immature rats causes long-term functional impairment. Whether this is associated with structural alterations remains controversial. The present study was designed to test the hypothesis that StE at an early age results in neuronal loss. StE was induced with lithium-pilocarpine in 12-d-old rats, and the presence of neuronal damage was investigated in the brain from 12 hr up to 1 week later using silver and Fluoro-Jade B staining techniques. Analysis of the sections indicated consistent neuronal damage in the central and lateral segments of the mediodorsal nucleus of the thalamus, which was confirmed using adjacent cresyl violet-stained preparations. The mechanism of thalamic damage (necrosis vs apoptosis) was investigated further using TUNEL, immunohistochemistry for caspase-3 and cytochrome c, and electron microscopy. Activated microglia were detected using OX-42 immunohistochemistry. The presence of silver and Fluoro-Jade B-positive degenerating neurons in the mediodorsal thalamic nucleus was associated with the appearance of OX-42-immunopositive activated microglia but not with the expression of markers of programmed cell death, caspase-3, or cytochrome c. Electron microscopy revealed necrosis of the ultrastructure of damaged neurons, providing further evidence that the mechanism of StE-induced damage in the mediodorsal thalamic nucleus at postnatal day 12 is necrosis rather than apoptosis. Finally, these data together with previously described functions of the medial and lateral segments of the mediodorsal thalamic nucleus suggest that some functions, such as adaptation to novelty, might become compromised after StE early in development.

Animals↗