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Neonatal asphyxia: vulnerability of basal ganglia, thalamus, and brainstem.

Two infants who suffered acute intrapartum asphyxia resulting in severe neonatal encephalopathy are described. Although computed tomography revealed no abnormalities, magnetic resonance imaging documented unequivocal lesions in the thalamus, basal ganglia, parasagittal cortex, brainstem tectum, and midline cerebellum in one patient and in the basal ganglia and parasagittal cortex in the other. Thus, magnetic resonance imaging was more sensitive than computed tomography in detecting acute brain damage after neonatal asphyxia and may become an important tool in improving our understanding of the relationship between adverse perinatal events, neonatal encephalopathy, and neurologic morbidity.

Asphyxia Neonatorum↗
PubMed1990

Increased gamma-hydroxybutyric acid receptors in thalamus of a genetic animal model of petit mal epilepsy.

The distribution and kinetics of specific binding sites for gamma-hydroxybutyrate (GHB), a naturally occurring compound known to produce absence-like seizures, was studied in the brains of Wistar rats with spontaneous, bilaterally synchronous spike wave discharges (SWDs), a model of petit mal epilepsy, and non-epileptic controls using [3H]GHB autoradiography. [3H]GHB receptor binding was increased 40-60% in lateral thalamic nuclei of the epileptic animals. Kinetic analysis showed that the increase in the binding was due to an increase in density of low affinity GHB binding sites in the epileptic animals. Given the ability of GHB to produce petit mal-like seizures when administered to animals, and the fact that the SWDs in the Wistar rat model seem to emanate from lateral thalamus, these data raise the possibility that GHB-mediated mechanisms may play a role in the pathogenesis of petit mal seizures.

Animals↗
PubMed2006

Excitotoxic lesions of the gustatory thalamus eliminate consummatory but not instrumental successive negative contrast in rats.

Lesions of the gustatory thalamus (GT) prevent the occurrence of between-session contrast effects (i.e., anticipatory negative contrast and consummatory successive negative contrast [cSNC]) involving liquid rewards. These deficits are attributed to a disruption of the reward comparison mechanism that computes the value of the current reward relative to the expected reward. Instrumental successive negative contrast (iSNC), which occurs following a surprising reduction in the magnitude of a solid food reward, is also keyed off the detection of a disparity between the value of the expected and actual rewards. The present study examined whether neurotoxic lesions of the GT prevent the occurrence of iSNC just as they abolish cSNC. In Experiment 1, both GT-lesioned and neurologically intact rats trained with 10 food pellets and shifted to one food pellet showed a significant iSNC effect. In Experiment 2, the same GT-lesioned rats failed to show cSNC when shifted from 1.0M sucrose to 0.15% sodium saccharin. The obtained pattern of results suggests that separate reward comparison mechanisms with different neural substrates underlie expression of cSNC and iSNC.

Animals↗
PubMed2003

Effects of excitotoxic lesions of the gustatory thalamus on latent inhibition and blocking of conditioned taste aversion in rats.

The influence of bilateral excitotoxic lesions of the gustatory thalamus on latent inhibition and blocking of conditioned taste aversion (CTA) was examined in two experiments. In Experiment 1, rats with thalamic lesions showed normal latent inhibition by acquiring a CTA that was significantly weaker when the conditioned stimulus (CS) was familiar than when it was novel. In Experiment 2, the preconditioned element (sodium chloride) of a compound CS blocked the acquisition of a CTA to the novel element (sucrose) in normal rats. Irrespective of whether sodium chloride was preconditioned or not, rats with thalamic lesions showed little or no aversion to sucrose following compound conditioning. Overall, the results provide no support for the experimental hypothesis that thalamic lesions disrupt decremental changes in the attentional processing of gustatory stimuli.

Acetic Acid↗
PubMed2006

GABA(B2) receptor subunit mRNA decreases in the thalamus of monoarthritic animals.

Many studies have implicated GABA(B) receptors in pain transmission mechanisms, especially in the spinal cord. In the thalamus, mRNA expression of the GABA(B(1b)) isoform was shown to be regulated in relay nuclei in response to chronic noxious input arising from experimental monoarthritis. GABA(B(1a)) and GABA(B2) mRNA expression was here determined by in situ hybridisation in the brain of control, 2, 4, 7 and 14 days monoarthritic rats, to evaluate whether this expression was regulated by chronic noxious input in thalamic nuclei. mRNA labelling was analysed quantitatively in the ventrobasal complex, posterior, central medial/central lateral and reticular thalamic nuclei; the thalamic visual relay and dentate gyrus were examined for control. No mRNA expression was detected for GABA(B(1a)) in control and monoarthritic animals. Similarly, GABA(B2) mRNA was not found in the reticular nucleus. However, GABA(B2) mRNA expression was observed in the ventrobasal complex, posterior and central medial/central lateral nuclei of control animals. A significant decrease of 42% at 2 days and 27% at 4 days of monoarthritis was observed in the ventrobasal complex contralaterally, when compared with controls, returning to basal levels at 7 days of monoarthritis. In the ipsilateral posterior nucleus, there was a significant decrease of 38% at 2 days of monoarthritis. No significant changes were observed in central medial/central lateral nuclei. The data suggest that GABA(B2) mRNA expression in the ventrobasal complex and posterior nucleus is regulated by noxious input and that GABA(B) receptors might play a role in the plasticity of these relay nuclei during chronic inflammatory pain.

Afferent Pathways↗
PubMed2005

Cortical activation with deep brain stimulation of the anterior thalamus for epilepsy.

OBJECTIVE: We studied the relation between thalamic stimulation parameters and the morphology, topographic distribution and cortical sources of the cerebral responses in patients with intractable epilepsy undergoing deep brain stimulation (DBS) of the thalamus. METHODS: Bipolar and monopolar stimuli were delivered at a rate of 2 Hz to the anterior (AN, four patients), the dorsomedian (DM, four patients), and the centromedian nucleus (CM, one patient) using the programmable stimulation device (Medtronic ITREL II). Source modeling was carried out by using statistical non-parametric mapping of low-resolution electromagnetic tomography (LORETA) values. RESULTS: All patients demonstrated reproducible time-locked cortical responses (CRs) consisting of a sequence of components with latencies between 20 and 320 ms. The morphology of these CRs, however, was very heterogeneous, depending primarily on the site of stimulation. Following AN stimulation, cortical activation was most prominent in ipsilateral cingulate gyrus, insular cortex and lateral neocortical temporal structures. Stimulation of the DM mainly showed activation of the ipsilateral orbitofrontal and mesial and lateral frontal areas, but also involvement of mesial temporal structures. Stimulation of the CM showed a rather diffuse (though still mainly ipsilateral) increase of cortical activity. The magnitude of cortical activation was positively related to the strength of the stimulus and inversely related to the impedance of the electrode. CONCLUSIONS: The pattern of cortical activation corresponded with the hodology of the involved structures and may underscore the importance of optimal localization of DBS electrodes in patients with epilepsy. SIGNIFICANCE: The method of analyzing sources of CRs could potentially be a useful tool for titration of DBS parameters in patients with electrode contacts in clinically silent areas. Furthermore, the inverse relation of the cortical activation and the impedance of the electrode contacts might suggest that these impedance measurements should be taken into consideration when adjusting DBS parameters in patients with epilepsy.

Adult↗
PubMed2005

Cholinergic nicotinic receptor involvement in movement disorders associated with Lewy body diseases. An autoradiography study using [(125)I]alpha-conotoxinMII in the striatum and thalamus.

The presence of alpha6 subunit containing nicotinic acetylcholine receptors on nigrostriatal dopaminergic neurons has been demonstrated in rodents and monkeys. [(125)I]alpha-conotoxinMII is a radioligand that binds to alpha6, and also alpha3 subunits of nicotinic acetylcholine receptors (nAChRs). In the present study, we have compared the distribution of [(125)I]alpha-conotoxinMII binding in post mortem human tissue from four groups of patients: individuals with dementia with Lewy bodies displaying extra-pyramidal features (DLB + EPF), DLB without extra-pyramidal features (DLB - EPF) Parkinson's disease without dementia (PD) and age-matched controls. Reduced binding was observed in the putamen and caudate in PD and both DLB groups. In DLB patients, the decline was greater in DLB + EPF compared to DLB - EPF group. The declines in nicotinic receptor binding in the striatum were in part paralleled by reductions in the striatal dopamine transporter. In the thalamus, [(125)I]alpha-conotoxinMII binding was significantly reduced in the centromedian nucleus in both DLB groups, and also in the parafascicular nucleus in the DLB - EPF group. In DLB + EPF and PD patients, there was decreased binding in the ventral lateral nucleus. This study demonstrates alterations of alpha6 and/or alpha3 nAChRs binding in DLB and PD, which are likely to relate to extra-pyramidal symptoms.

Aged↗
PubMed2005

Auditory thalamus responses to guinea-pig vocalizations: a comparison between rat and guinea-pig.

Although neuronal responses to species-specific vocalizations have long been described, very few between-species comparisons have been made. In a previous study, a differential representation of species-specific vocalizations was found in the auditory cortex (ACx): marmoset ACx neurons responded more, and more selectively, to marmoset calls than did cat ACx neurons [Wang, X., Kadia, S.C., 2001. Differential representation of species-specific primate vocalizations in the auditory cortices of marmoset and cat. J. Neurophysiol. 86, 2616-2620]. The present study analyzed responses of guinea-pig and rat auditory thalamus neurons to four well-defined guinea-pig vocalizations. Neurons of guinea-pigs (n = 96) and rats (n = 87) displayed similar response strength to guinea-pig vocalizations, and did not exhibit a preference for the natural over the time-reversed version of the calls in both species. This difference with the study by Wang and Kadia might suggest that, in mammals, the selectivity for the natural version of species-specific vocalizations is prominent only at the cortical level.

Animals↗
PubMed2004

A laser micromachined probe for recording multiple field potentials in the thalamus.

Multichannel recording provides integral information about electrical brain activities at one instant in time. In this study, multielectrode probes were fabricated to record the thalamic field potentials (FPs) responding to the electrical stimulation of nerve at the rat tail. At first, the number of sweeps used to form the evoked FP average and the spatial sampling density were determined by using cross-correlation functions, which were then statistically analyzed. The difference was significant at P < 0.05, if the number of sweeps for averaging was more than 50 and the spatial interval between two consecutive recording sites was less than 50 microm in the anteroposterior, mediolateral and ventrodorsal directions. The responsive area was distributed vertically in the thalamus (ventral posterior lateral (VPL) nucleus); therefore, the recording sites were arranged in one linear array. Sixteen recording sites, which were 50 microm apart from each other, were distributed in the ventrodorsal direction. A 16-channel silicon probe was fabricated by using a standard photolithography process and laser micromachining techniques. The probe provides capabilities to record multiple thalamic evoked FPs and multiunit activities simultaneously.

Animals↗
PubMed2003

Differential activities of Sonic hedgehog mediated by Gli transcription factors define distinct neuronal subtypes in the dorsal thalamus.

The dorsal thalamus (DT) is a pivotal region in the vertebrate brain that relays inputs from the peripheral sensory organs to higher cognitive centers. It consists of clusters of neurons with relevant functions, called brain nuclei. However, the mechanisms underlying development of the DT, including specification of the neuronal subtypes and morphogenesis of the nuclear structures, remain largely unknown. As a first step to this end, we focused on two transcription factors Sox14 and Gbx2 that are expressed in the specific brain nuclei in the chick DT. The onset of their expression was found in distinct populations of the postmitotic cells in the prosomere 2, which was regulated by the differential activities of Sonic hedgehog (Shh) in a manner consistent with the action as a morphogen. Furthermore, both gain- and loss-of-function results strongly suggest that such distinct inductive activities are mediated selectively by different Gli factors. These results suggest that cooperation of the differential expression of Gli factors and the activity gradient of Shh signaling generates the distinct thalamic neurons at the specific locations.

Animals↗
PubMed2004

Involvement of alpha6/alpha3 neuronal nicotinic acetylcholine receptors in neuropsychiatric features of Dementia with Lewy bodies: [(125)I]-alpha-conotoxin MII binding in the thalamus and striatum.

Dementia with Lewy bodies (DLB) is a neurodegenerative disease associated with a range of neuropsychiatric symptoms and reduced expression of neuronal nicotinic acetylcholine receptors (nAChRs) in neocortex, hippocampus, thalamus and basal ganglia. To determine whether there are selective associations between alterations in alpha6/alpha3 neuronal nicotinic acetylcholine receptors (nAChRs) and the two key neuropsychiatric features of DLB, impaired consciousness (IC) and visual hallucinations (VH), quantitative [(125)I]-alpha-conotoxin MII ([(125)I]-alpha-Ctx MII) autoradiography was undertaken on 28 people with DLB and 15 control cases from the Newcastle Brain Bank. There was a highly significant overall trend for reduced thalamic [(125)I]-alpha-Ctx MII binding in DLB (p < 0.001), with significant deficits in the centromedian, ventral lateral and ventroposterior medial thalamic nuclei (p < 0.05), together with caudate and putamen (p < 0.001). [(125)I]-alpha-Ctx MII binding was significantly lower in DLB cases with IC than without IC in the putamen (p < 0.05), however there was no significant association between [(125)I]-alpha-Ctx MII binding and VH. Reductions in [(125)I]-alpha-Ctx MII binding in caudate and putamen were paralleled by similar reductions in [(125)I]PE2I binding. [(125)I]PE2I binding was also significantly lower in DLB cases with IC than without IC in the caudate (p < 0.05) and putamen (p < 0.001). These results demonstrate that deficits in alpha6/alpha3 nAChRs occur in specific brain regions in DLB, may in part be related to the loss of dopaminergic neurons and may contribute to the development of impaired consciousness in the disorder.

Aged↗
PubMed2005

Timing and prediction the code from basal ganglia to thalamus.

When is an inhibitory synapse not inhibitory? In this issue of Neuron, Person and Perkel demonstrate that thalamic neurons can translate extrinsic GABAergic input from the basal ganglia into highly precise patterns of sustained spiking in a circuit that is essential for vocal learning in songbirds. Postinhibitory rebound serves as a mechanism that preserves precise spike timing information, enabling reliable propagation of activity throughout this pathway. The results have broad implications for basic mechanisms of functional processing in both thalamus and basal ganglia and serve to increase our understanding of how acoustic units of vocal sounds are transformed into motor gestures during the sensitive period for song learning.

Animals↗
PubMed2005

Local axon guidance in cerebral cortex and thalamus: are we there yet?

Normal brain function requires the development of precise connections between thalamus and cerebral cortex. In this issue of Neuron, Cang et al. and Tori and Levitt argue that EphA/ephrin-A signaling in the target tissue guides sensory thalamic axons to the correct cortical area, and sensory cortical axons to precise thalamic targets. Although EphA/ephrin-A signaling organizes sensory maps within areas, and thalamocortical axons in the internal capsule, both papers argue that each developmental event is dissociable from the others.

Animals↗
PubMed2004

Naloxone-induced morphine withdrawal increases the number and degranulation of mast cells in the thalamus of the mouse.

Naloxone-induced jumping in morphine-dependent mice is inhibited by cromolyn, a mast cell stabilizer, suggesting that this characteristic withdrawal behavior results from degranulation of mast cells. Because withdrawal is considered as a central phenomenon, degranulation of mast cells located within the CNS may influence aspects of opioid withdrawal. The present study evaluates histologically whether naloxone, injected into opioid dependent mice, induces degranulation of mast cells. Seventy-two hours after the s.c. implantation of a 75 mg morphine pellet, the number and degranulation of thalamic mast cells did not differ from those in placebo-implanted controls. However, two injections of 50 mg/kg of naloxone, 30 and 60 min before tissue collection, increased the number of degranulated mast cells compared to those in mice injected with saline. Analysis throughout the entire thalamus (90 40-micro sections) revealed increases in the total number of mast cells as well as the number that were degranulated, especially in sections 52-60, corresponding to Bregma -2.18 to 2.54. Here, mast cells were clustered in the IGL and VPL/VPM nuclei, and redistributed from the ventromedial to the dorsolateral aspects of the Po and PF nuclei during withdrawal. Degranulation was also greater throughout the LD, LP nuclei during withdrawal. These data reveal a novel neuroimmune reaction to opioid withdrawal in the CNS.

Animals↗
PubMed2005

Spatial and temporal visual properties of single neurons in the suprageniculate nucleus of the thalamus.

The spatial and temporal visual sensitivity to drifting sinusoidal gratings was studied in 105 neurons of the suprageniculate nucleus of the feline thalamus. Extracellular single-unit recordings were performed in halothane-anesthetized, immobilized, artificially ventilated cats. Most suprageniculate nucleus cells were strongly sensitive to the direction of drifting gratings. The suprageniculate nucleus units had a clear preference for very low spatial frequencies with a mean of 0.05 cycle/deg. The spatial resolution was also very low with a mean of 0.16 cycle/deg. Most of the cells displayed low-pass spatial tuning characteristics, while the remainder of the units were band-pass tuned. The suprageniculate nucleus units were extremely narrowly tuned, to spatial frequencies with a mean spatial bandwidth of 1.07 octaves. A majority of the units responded optimally to high temporal frequencies, with a mean of 8.53 Hz. The temporal frequency tuning functions predominantly revealed a band-pass character, with a mean temporal bandwidth of 1.66 octaves. These results demonstrate that the neurons in the suprageniculate nucleus display particular spatial and temporal characteristics. The spatial and temporal tuning properties of the suprageniculate nucleus neurons are very similar to those of the superior colliculus and the anterior ectosylvian cortex, structures that provide the main visual afferentation toward the suprageniculate nucleus. This suggests their common function in motion perception, and especially in the recording of movements of the visual environment relative to the body, and the related behavioral action.

Animals↗
PubMed2006

Histometric changes and cell death in the thalamus after neonatal neocortical injury in the rat.

Freezing injury to the developing cortical plate results in a neocortical malformation resembling four-layered microgyria. Previous work has demonstrated that following freezing injury to the somatosensory cortex, males (but not females) have more small and fewer large cells in the medial geniculate nucleus. In the first experiment, we examined the effects of induced microgyria to the somatosensory cortex on neuronal numbers, neuronal size, and nuclear volume of three sensory nuclei: ventrobasal complex, dorsal lateral geniculate nucleus, and medial geniculate nucleus. We found that there was a decrease in neuronal number and nuclear volume in ventrobasal complex of microgyric rats when compared with shams, whereas there were no differences in these variables in the dorsal lateral geniculate nucleus or medial geniculate nucleus. We also found that there were more small and fewer large neurons in both ventrobasal complex and medial geniculate nucleus. In experiment 2, we attempted to determine the role of cell death in the thalamus on these histometric measures. We found that cell death peaked within 24 h of the freezing injury and was concentrated mostly in ventrobasal complex. In addition, there was evidence of greater cell death in males at this age. Taken together, these results support the notion that males are more severely affected by early injury to the cerebral cortex than females.

Age Factors↗
PubMed2005

Effects of orexins/hypocretins on neuronal activity in the paraventricular nucleus of the thalamus in rats in vitro.

Orexin-A (ORX-A) and orexin-B (ORX-B), also called hypocretin-1 and hypocretin-2, respectively, act upon orexin 1 (OX1R) and orexin 2 (OX2R) receptors, and are involved in the regulation of sleep-wakefulness and energy homeostasis. Orexin neurons in the lateral hypothalamic perifornical region project heavily to the paraventricular nucleus of the thalamus (PVT), which is deeply involved in the control of motivated behaviors. In the present study, electrophysiological and cytosolic Ca2+ concentration ([Ca2+]i) imaging studies on the effects of ORX-A and ORX-B on neurons in the PVT were carried out in rat brain slice preparations. ORX-A and/or ORX-B were applied extracellularly in the perfusate. Extracellular recordings showed that about 80% of the PVT neurons were excited dose-dependently by both ORX-A and ORX-B at concentrations of 10(-8) to 10(-6)M, and the increase in firing rate was about three times larger for ORX-B than for ORX-A at 10(-7)M. When both ORX-A and ORX-B were applied simultaneously at 10(-7)M, the increase in firing rate was almost equal to that of ORX-B at 10(-7)M, suggesting that the PVT neurons do not show a high affinity to ORX-A which is expected if they have OX1R receptors. The excitatory effect of ORX-B was seen in low Ca2+ and high Mg2+ ACSF as well as in normal ACSF, and the increase in firing rate was greater in low Ca2+ and high Mg2+ ACSF than in normal ACSF. [Ca2+]i imaging studies demonstrated that [Ca2+]i was increased in about 50% of the PVT neurons by both 10(-7)M ORX-A and ORX-B with a stronger effect for ORX-B, and the increase in [Ca2+]i induced by ORX-B was abolished in Ca2+-free ACSF, suggesting that ORX-B does not release Ca2+ from intracellular Ca2+ stores. Subsequent whole cell patch clamp recordings revealed that an after hyperpolarization seen following each action potential in normal ACSF disappeared in Ca2+-free ACSF, and the mean magnitude of the depolarization induced by ORX-B was same in normal, Ca2+-free and TTX-containing Ca2+-free ACSFs. Furthermore, ORX-B-induced depolarization was reversed to hyperpolarization when membrane potential was lowered to about -97 mV, and an increase of extracellular K+ concentration from 4.25 to 13.25 mM abolished the ORX-B-induced depolarization, indicating that the ORX-B-induced depolarization is associated with an increase in the membrane resistance resulting from a closure of K+ channels. These results suggest that orexins depolarize and excite post-synaptically PVT neurons via OX2R receptors, and that orexin-activated PVT neurons play a role in the integration of sleep-wakefulness and energy homeostasis, and in the control of motivated behaviors.

Action Potentials↗
PubMed2006

Inhibitory circuits in the thalamus and hippocampus--an appraisal after 40 years.

After scientific successes in the study of synaptic activation and inhibition of motoneurons and unraveling mechanisms underlying presynaptic inhibition, Sir John Eccles was interested in studying synaptic mechanisms governing the activity of neurons in the brain stem, cerebellum, and various cortical areas. In this new arena, his group discovered several principles, which have later been shown to generalize across brain structures and have substantial functional significance. Among these were the first identification and location of inhibitory synapses in the cerebral cortex and recurrent inhibitory systems in the hippocampus, cerebellum, and thalamus.

Animals↗