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Flupirtine depresses nociceptive activity evoked in rat thalamus.

Flupirtine, a novel analgesic agent, was tested on nociceptive activity in neurones of the dorsomedial part of the ventral nucleus of the thalamus (VDM) and ascending axons of the spinal cord of rats under urethane anaesthesia. Activity was elicited by supramaximal stimulation of the sural nerve. Flupirtine injected i.v. dose dependently reduced nociceptive activity in the thalamus and ascending axons. The ED50 of flupirtine in depressing the thalamic response was 1.9 mg/kg, and the ED50 in depressing the C fibre-evoked response in ascending axons was 18 mg/kg. Naloxone reduced the depression of the nociceptive response evoked in the thalamus when applied before but not when applied after flupirtine. The results indicate that flupirtine produces analgesia by spinal inhibition of nociceptive impulse transmission from afferent nerve fibres to neurones sending their axons to the brain and, in addition, by supraspinal inhibition of nociceptive impulse transmission to the thalamus. Opioid mechanisms could be involved in these effects.

Afferent Pathways↗

Observations on the development of certain ascending inputs to the thalamus in rats. I. Postnatal development.

We have studied the postnatal development of the major ascending afferents to the thalamus in postnatal rats using tetramethylbenzidine histochemistry following wheat germ agglutinin-conjugated horseradish peroxidase injections into either the dorsal column nuclei, the deep cerebellar nuclei, or the inferior colliculus. By the day of birth, the efferents from each of these regions have already entered, and arborized extensively within, their appropriate thalamic relay nuclei. However, the overall distribution of each of these ascending afferent systems differs dramatically from that seen in mature rats. In neonatal rats, a substantial proportion of the ascending axons extend beyond the thalamus and often enter the internal capsule, some bypassing the thalamus altogether. In addition, some of the axons which enter and arborize within the thalamus extend beyond their appropriate terminal field into adjoining thalamic nuclei. Retrograde tracing experiments utilizing Fast blue indicate that the cells of origin of these overshooting axons are distributed similarly to the cells of origin of the definitive thalamic afferents. These early erroneous projections are all subsequently eliminated and the characteristically restricted adult distribution of each afferent system is evident by P30. These results indicate that developmental overgrowths and targeting errors of thalamic afferent fibers are not unique to the visual system (where they have been documented previously), but may be a general feature in the development of these pathways.

Afferent Pathways↗

Distribution of AMPA selective glutamate receptors in the thalamus of adult rats and during postnatal development. A light and ultrastructural immunocytochemical study.

The regional, cellular and subcellular distribution of AMPA receptors was demonstrated immunocytochemically within the thalamus of adult and young (from 1 to 20 days postnatal, P1-P20) rats. The antipeptide antibodies used recognize individual subunit proteins of the AMPA-preferring glutamate receptor, i.e., GluR1, GluR2-3 and GluR4. Our results demonstrate that these AMPA receptor subunits are generally not highly expressed in the thalamus, as compared to other brain areas and that they are enriched differentially within different thalamic nuclei. GluR1 is mostly found in intralaminar and midline nuclei throughout life, whereas GluR2-3 is moderately expressed in the thalamus, with no major developmental changes. GluR4 is the predominant subunit expressed in the reticular nucleus in adult rats, but not in young animals, where until P9 it is instead present in the ventrobasal complex. Samples of paraventricular and lateral geniculate nuclei stained with GluR1 and of reticular nucleus as well as ventrobasal complex stained with GluR4 were used for the ultrastructural study. In all the samples, labelling was in the somatic and dendritic cytoplasm, with dense patches of reaction product apposing post-synaptic densities of terminals with round clear vesicles and asymmetric specializations. Glial staining was observed only with the GluR1 antiserum and there was no evidence of labelled synaptic terminals. The differential distribution of GluR subunits in the thalamus suggests that certain subunits may participate more than others in mediating post-synaptic responses in distinct neuronal populations and also that other GluR types may be involved in the thalamic networks.

Aging↗

Morphological changes in the thalamus and neocortex of the cat brain after a restricted unilateral fetal neocortical lesion.

In order to study the response of the brain to injury during early development, the neocortex of ten fetal kittens was lesioned at age E43-48, in either the frontal (n = 8) or parieto-occipital (n = 2) areas. The thalamus and neocortex of the lesioned animals were analyzed using quantitative morphometry and compared to intact control cats (n = 10). Ipsilaterally, the volumes of the remaining neocortex and of the thalamus were 26.5% and 25.7% smaller, respectively (P < 0.05). Contralaterally, the neocortex did not change in volume, whereas the thalamus tended to be smaller by a mean of 11.1%. Ipsilaterally, in all four thalamic nuclei studied, the neuronal and glial cell packing densities (NCPD and GCPD) and the cross sectional area of neuronal somata did not differ between lesioned and intact animals except for the principal ventromedial nucleus, where the GCPD was significantly lower (P < 0.05) in lesioned animals. Contralaterally, the NCPD and GCPD did not show any differences between groups, except for the principal ventromedial nucleus, in which the GCPD was lower in lesioned cats (P < 0.05). Furthermore, in the contralateral basal ventromedial nucleus, the cross sectional area of the neuronal somata was smaller in lesioned than in intact animals (P < 0.01). These results indicate loss of neurons and glia in the ipsilateral thalamus and probably in the neocortex. Since, at the time of the cortical resection, transient reciprocal thalamosubplate connections have been established in the cat, the lesion-induced deprivation of subplate target neurons and cortical inputs probably precluded the survival of a substantial number of developing thalamic neurons. In the cortex the hypothetical loss of neurons may, at least partly, be attributed to lesion-induced elimination of target neurons before establishment of corticocortical connections.

Animals↗

The differential synaptic organization of the spinal and lemniscal projections to the ventrobasal complex of the rat thalamus. Evidence for convergence of the two systems upon single thalamic neurons.

The synaptic organization of terminals originating either from the spinal cord (spinothalamic) or from the dorsal column nuclei (lemniscal) was investigated in the ventrobasal complex of the rat thalamus. Wheatgerm agglutinin conjugated to horseradish peroxidase was used as an anterogradely transported axonal tracer, using benzidine dihydrochloride as a chromogen for the identification by electron microscopy of spinal and lemniscal projections to the ventrobasal thalamus. A double anterograde tract tracing strategy, based labeling by wheatgerm agglutinin conjugated to horseradish peroxidase of spinal terminals and simultaneous visualization of lemniscal terminals identified by Wallerian degeneration induced by lesion of the neurons of origin in the dorsal column nuclei, was used to compare the postsynaptic elements contacted by the two pathways and to look for a possible convergence of the two pathways onto single thalamic neurons. Spinal and lemniscal terminals are large (2-2.5 microns mean average diameter) terminals containing several mitochondria and numerous rounded vesicles. A quantitative analysis of the mean average diameters of the terminals revealed that one could not differentiate between synapses formed by the two pathways on a morphological basis. Terminals of the two pathways make asymmetrical contacts (Gray type I) with dendrites of varying diameter, dendritic protrusions, and cell somata. A quantitative analysis of the least diameter of the postsynaptic elements demonstrates projections of the two systems to different, partially overlapping regions of thalamic neurons. Lemniscal terminals originating from the dorsal column nuclei frequently contact cell somata; axosomatic spinothalamic contacts are uncommon. In addition, lemniscal projections tend to contact more proximal dendrites than do spinal projections, and this differential synaptic organization is statistically significant. From a functional point of view, this differential synaptic organization might indicate that lemniscal inputs have greater influence than spinal inputs in affecting the activity of thalamic neurons. Labeled spinothalamic terminals contact the same dendritic profile as do degenerating lemniscal terminals in about 10% of single sections. Because the present study did not include a complete reconstruction of ventrobasal complex neurons of the thalamus or even regions of dendritic arbors, the degree of convergence is likely to be significantly underestimated. These findings indicate that the anatomical basis exists for an interaction between nociceptive and non-nociceptive somesthetic systems at the level of single ventrobasal neurons of the thalamus of the rat.

Animals↗

Spinal lamina I projection neurons in the rat: collateral innervation of parabrachial area and thalamus.

A major ascending nociceptive pathway from spinal lamina I to the mesencephalon has previously been reported in the cat, rat and monkey. In the present paper, we have used single and double retrograde labeling techniques to describe this projection system and its collateralization to the thalamus in the rat. Injections of wheat germ agglutinin-horseradish peroxidase into the pontomesencephalic parabrachial area labeled cell bodies bilaterally in lamina I and deeper laminae of the spinal cord. Bilateral lesions of the dorsolateral funiculi at thoracic levels reduced labeling of lamina I neurons caudal to the lesions. Combined injections of fluorescent retrograde tracers into the lateral thalamus and parabrachial area resulted in double labeling of projection neurons in lamina I, lamina IV VIII and the lateral spinal nucleus of the cervical and lumbar enlargements. Double-labeled neurons were especially abundant in lamina I. Thus, we have demonstrated a major lamina I projection through the dorsolateral funiculi to the parabrachial area with significant collateralization to the thalamus. Moreover, since more than 80% of retrogradely labeled lamina I spinothalamic tract cells had collaterals to the parabrachial area we have indirectly demonstrated the presence of a dorsolateral funicular pathway for lamina I spinothalamic neurons in the rat. More lamina I neurons were retrogradely labeled from midbrain injections as compared to thalamic injections. The significance of these findings rest on previous work in this and other laboratories and concerns the understanding of spinal nociceptive mechanisms. Lamina I projection neurons are primarily nociceptive-specific in their response properties and have been shown to project to both the midbrain and thalamus via the dorsolateral funiculus in a number of species. The role of this projection system in nociceptive transmission may lie in its ability to distribute precise information to multiple brain stem sites which in turn activate autonomic or affective responses or descending pain modulatory mechanisms.

Animals↗

Single cholinergic mesopontine tegmental neurons project to both the pontine reticular formation and the thalamus in the rat.

Microinjections of the cholinergic agonist carbachol into a caudal part of the pontine reticular formation of the rat induce a rapid eye movement sleep-like state. This carbachol-sensitive region of the pontine reticular formation is innervated by cholinergic neurons in the pedunculopontine and laterodorsol tegmental nuclei. The same population of cholinergic neurons also project heavily to the thalamus, where there is good evidence that acetylcholine facilitates sensory transmission and blocks rhythmic thalamocortical activity. The present study was undertaken to examine the degree to which single cholinergic neurons in the mesopontine tegmentum project to both the carbachol-sensitive region of the pontine reticular formation and the thalamus, by combining double fluorescent retrograde tracing and immunofluorescence with a monoclonal antibody to choline acetyltransferase in the rat. The results indicated that a subpopulation (5-21% ipsilaterally) of cholinergic neurons in the mesopontine tegmentum projects to both the thalamus and the carbachol-sensitive site of the pontine reticular formation, and these neurons represented the majority (45-88%) of cholinergic neurons projecting to the pontine reticular formation site. The percentage of cholinergic neurons with dual projections was higher in the pedunculopontine tegmental nucleus (6-27%) than in the laterodorsal tegmental nucleus (4-11%). In addition, mixed with cholinergic neurons in the mesopontine tegmentum, there was a small population of dually projecting neurons that did not appear to be cholinergic. Mesopontine cholinergic neurons with dual projections may simultaneously modulate neuronal activity in the pontine reticular formation and the thalamus, and thereby have the potential of concurrently regulating different aspects of rapid eye movement sleep.

Animals↗

Prenatal development of calbindin immunoreactivity in the dorsal thalamus of the rat.

The distribution of calbindin immunoreactivity was studied in the developing rat dorsal thalamus at embryonic days 14, 16, 18 and 20. At early stages (days 14-16), calbindin is expressed throughout the dorsal thalamic cell mass. Most intense labeling occurs in cells adjacent to the ventricular surface, in a spatial gradient reflecting the well-known outside-in generation pattern. Between days 16 and 20, calbindin-positive periventricular cells are redistributed in the dorsal thalamus according to two different patterns. They first become oriented tangentially within the periventricular layer, and diminish in number at the central locus where midline thalamic fusion occurs at 18 days. Periventricular calbindin immunoreactivity becomes restricted to a ring of late-born cells surrounding the gray commissure. Recognizable portions of this ring-shaped primordium will mature forming n.paratenialis, n.reuniens, n.paraventricularis, and n.subparafascicularis magnocellularis. Simultaneously, a massive contingent of radially-oriented, fusiform, calbindin-positive young neurons extends from the periventricular ring-shaped aggregate to the lateral brain surface at the caudoventral pole of the dorsal thalamus at embryonic days 17/18. These cells surround the primordium of the medial geniculate body, participating in the constitution of its marginal zone, and invade the lateral posterior nucleus, accumulating within its caudomedial part. Other portions of this stream form the parvocellular subparafascicular nucleus and the peripeduncular nucleus. The observed patterns of calbindin expression suggest that dorsal thalamic postmitotic neurons transiently express the marker during initial phases of axogenesis, whereas a specific, late-born population expresses calbindin continuously into adulthood. This late subpopulation displays migratory behavior, and finally subdivides into several nuclei of the mature midline, superficial and posterior thalamus.

Animals↗

Release of the nitric oxide precursor, arginine, from the thalamus upon sensory afferent stimulation, and its effect on thalamic neurons in vivo.

The neurophysiology and neuroanatomy of the thalamus have been extensively studied in a variety of species and sensory systems. The identity of the neurotransmitter(s) which mediate the excitation from ascending sensory afferents on to thalamic relay neurons is, however, still unclear, although it appears to be a substance which is a ligand for excitatory amino acid receptors, as the responses of ventrobasal thalamus neurons to natural stimulation of somatosensory afferents arising from the mustachial vibrissae of the rat are mediated by ionotropic excitatory amino acid receptors, when stimulation is performed using an air-jet directed at the vibrissa receptor field. In an effort to determine the transmitter of these sensory afferents, we have attempted to detect the release of amino acids in the ventrobasal thalamus in vivo upon such stimuli. We have thus used a similar natural stimulation protocol, together with push-pull perfusion and recording in the ventrobasal thalamus, and we describe the release of the amino acid, arginine, in this brain area following physiological stimulation of afferents. Furthermore, we show that application of L-arginine on to thalamic relay neurons can facilitate sensory synaptic transmission, possibly via the synthesis of the diffusable messenger, free radical gas, nitric oxide. This may represent a novel, local positive-feedback, modulatory system which could enhance the responsiveness of thalamic neurons to sensory input.

Afferent Pathways↗

The mediodorsal nucleus of the thalamus in rats--I. forebrain gabaergic innervation.

The aim of this study was to determine whether forebrain neurons projecting to the mediodorsal nucleus of the thalamus in rats express glutamate decarboxylase messenger RNA as a marker for GABAergic neurons. Forebrain glutamate decarboxylase messenger RNA-containing neurons that project to the mediodorsal nucleus were identified using a combination of retrograde tracing with Fluoro-Gold and in situ hybridization for the messenger RNA encoding the 67,000 molecular weight synthetic enzyme for GABA. Glutamate decarboxylase messenger RNA-containing afferents to the mediodorsal nucleus were observed in the olfactory tubercle, vertical limb of the diagonal band of Broca, ventral pallidum, sublenticular substantia innominata, globus pallidus, lateral preoptic area, bed nucleus of the stria terminalis and reticular nucleus of the thalamus. The largest proportions of glutamate decarboxylase messenger RNA-containing afferents to the mediodorsal nucleus were observed in the vertical limb of the diagonal band, ventral pallidal parts of the olfactory tubercle and the reticular nucleus of the thalamus. Somewhat fewer glutamate decarboxylase messenger RNA-containing, retrogradely labeled neurons were observed in the subcommissural ventral pallidum and sublenticular substantia innominata. These data suggest that a GABAergic projection from the basal forebrain to the mediodorsal nucleus of the thalamus can influence the function of this nucleus.

Animals↗

Early development of the human thalamus: Golgi and Nissl study.

Qualitative and quantitative parameters of the early neuronal development of the thalamus were examined in human embryos and fetuses ranging in age from 5-16 gestational weeks (g.w.) using Nissl stained and Golgi impregnated tissue. In the earliest period analyzed, from 5-6 weeks of gestation, dorsal and ventral parts of the human thalamus were poorly differentiated structures forming the sides of the third ventricle. At 6 g.w., the prospective thalamic anlage consisted of the ventricular (VZ), the intermediate (IZ) and the marginal zones (MZ). The neurons in the VZ were bipolar and radially arranged to the ventricular surface. From 6-8 gestational weeks detached bipolar or branched bipolar cells with horizontal or oblique orientation were encountered in the IZ and occasionally in the MZ. In the period between 10-14 weeks of gestation, segregation of neurons into different thalamic nuclei began. The lateral geniculate nucleus, centrum medianum and mediodorsal nucleus were the first to be distinguished. In comparison with the previous period, the neurons throughout the rostro-caudal axis of the thalamus were more differentiated, with a higher number of primary dendrites that were often bifurcated. This resulted in various shapes of immature neurons: simple uni- and bipolar (type 1), branched uni- and bipolar (type 2) and young multipolar (type 3). In addition, the first spines were frequently observed on dendrites at 12 weeks of gestation. At 14-16 weeks of gestation, segregation of the neurons into thalamic nuclei continued. The neurons exhibited further dendritic differentiation that followed the caudo rostral gradient. For the first time, multipolar neurons, especially in the caudal part, could be subdivided into two classes: multipolar with a 'bushy' appearance, the result of many primary dendrites with several bifurcations and 'simpler' multipolar neurons with fewer and less branched primary dendrites. Neuronal differentiation was further expressed by an increase in the total dendritic length and somatic surface, up to six and three times, respectively, from the earliest period analyzed to 16 weeks of gestation. Dendritic length increased initially by the formation of new primary branches and their elongation and secondly by formation of higher branch orders. At 16 g.w., a group of immature cells were observed dorsally, on the frontal sections through the rostral thalamus. Its ganglionic eminence origin is discussed.

Analysis of Variance↗

Cyto- and chemoarchitecture of the dorsal thalamus of the monotreme Tachyglossus aculeatus, the short beaked echidna.

We have examined the cyto- and chemoarchitecture of the dorsal thalamus of the short beaked echidna (Tachyglossus aculeatus), using Nissl and myelin staining, immunoreactivity for parvalbumin, calbindin, calretinin and non-phosphorylated neurofilament protein (SMI-32 antibody), and histochemistry for acetylcholinesterase and NADPH diaphorase. Immunohistochemical methods revealed many nuclear boundaries, which were difficult to discern with Nissl staining. Parvalbumin immunoreactive somata were concentrated in the ventral posterior, reticular, posterior, lateral and medial geniculate nuclei, while parvalbumin immunoreactivity of the neuropil was present throughout all but the midline nuclei. Large numbers of calbindin immunoreactive somata were also found within the midline thalamic nuclei, and thalamic sensory relay nuclei. Immunoreactivity for calretinin was found in many small somata within the lateral geniculate "a" nucleus, with other labelled somata found in the lateral geniculate "b" nucleus, ventral posterior medial and ventral posterior lateral nuclei. Immunoreactivity with the SMI-32 antibody was largely confined to somata and neuropil within the thalamocortical relay nuclei (ventral posterior medial and lateral nuclei, lateral and medial geniculate nuclei and the posterior thalamic nucleus). In broad terms there were many similarities between the thalamus of this monotreme and that of eutheria (e.g. disposition of somatosensory thalamus, complementarity of parvalbumin and calbindin immunoreactive structures), but there were some unique features of the thalamus of the echidna. These include the relatively small size of the thalamic reticular nucleus and the preponderance of calbindin immunoreactive neurons over parvalbumin immunoreactive neurons in the ventral posterior nucleus.

Acetylcholinesterase↗

Distribution of the dopamine innervation in the macaque and human thalamus.

We recently defined the thalamic dopaminergic system in primates; it arises from numerous dopaminergic cell groups and selectively targets numerous thalamic nuclei. Given the central position of the thalamus in subcortical and cortical interplay, and the functional relevance of dopamine neuromodulation in the brain, detailing dopamine distribution in the thalamus should supply important information. To this end we performed immunohistochemistry for dopamine and the dopamine transporter in the thalamus of macaque monkeys and humans to generate maps, in the stereotaxic coronal plane, of the distribution of dopaminergic axons. The dopamine innervation of the thalamus follows the same pattern in both species and is most dense in midline limbic nuclei, the mediodorsal and lateral posterior association nuclei, and in the ventral lateral and ventral anterior motor nuclei. This distribution suggests that thalamic dopamine has a prominent role in emotion, attention, cognition and complex somatosensory and visual processing, as well as in motor control. Most thalamic dopaminergic axons are thin and varicose and target both the neuropil and small blood vessels, suggesting that, besides neuronal modulation, thalamic dopamine may have a direct influence on microcirculation. The maps provided here should be a useful reference in future experimental and neuroimaging studies aiming at clarifying the role of the thalamic dopaminergic system in health and in conditions involving brain dopamine, including Parkinson's disease, drug addiction and schizophrenia.

Aged↗

Instructive role of a peripheral pattern for the central patterning of the trigeminal projection at the brainstem and thalamus revealed by an artificially altered whisker pattern.

The central patterning mechanism of neuronal circuits is an important issue in developmental neuroscience. We report here the role of a peripheral whisker pattern for the patterning of the trigeminal projection at the brainstem and thalamus in the mouse somatosensory system. The whisker pattern was manipulated by infecting the embryonic epidermis with adenovirus harboring Shh. The ectopic expression of Shh led to the induction of extra whiskers and displacement of whiskers, where these whiskers were histologically normal. The altered whisker pattern was isomorphically represented in the brainstem (barrelette: subnuclei principalis and subnuclei interpolaris), thalamus (barreloid) and cortex (barrel) as revealed by cytochrome oxidase staining. The barrelette-like pattern of the parvalbumin became discernible by immunostaining at P7 in subnuclei principalis and at P4 in subnuclei interpolaris in normal mice. These are the barrelette neurons projecting to the thalamus and the local circuit within the barrelette. The barrelette-like parvalbumin pattern also exhibits the altered whisker pattern induced by the adenovirus harboring Shh. These results highlight the role the peripheral whisker pattern for the central patterning of the brainstem, thalamus, and cortex in the mouse somatosensory system.

Adenoviridae↗

Differential expression of mitogen-activated protein kinases and immediate early genes fos and jun in thalamus in schizophrenia.

Despite a growing body of evidence demonstrating that mitogen-activated protein (MAP) kinase pathways play an important physiological role in the CNS, little is known about their role and function in various mental disorders including schizophrenia. Our previous studies have shown increased expression of several intermediates of the extracellular signal-regulated (ERK) cascade and downstream transcription targets in cerebellar vermis without any changes in mesopontine tegmentum and Brodmann's area 10 in patients with schizophrenia. Given the evidence for abnormalities in schizophrenia in a neural circuit involving the cerebellum and thalamus, the present study was conducted to examine the expression of MAP kinases extracellular signal-regulated kinase (ERK), c-Jun-N-terminal kinase (JNK) and p38, as well as immediate early genes fos (c-fos and fos B) and jun (c-jun, jun B and jun D) using a Western blot analysis and reverse transcription polymerase chain reaction (RT-PCR) in postmortem thalamus from schizophrenic and control subjects. There were significant increase in ERK2, c-fos and c-jun protein and mRNA levels in thalamus of patients with schizophrenia relative to controls. No statistically significant differences were found for ERK1, Fos B, Jun B or Jun D proteins in schizophrenic and control subjects. These results taken together with our previous findings provide new evidence for selective abnormalities of distinct MAP kinases and immediate early genes c-fos and c-jun in a circuit involving the thalamus and cerebellum, which may contribute significantly to the pathophysiology of schizophrenia.

Adult↗

Magnetic resonance spectroscopy of the thalamus in patients with typical absence epilepsy.

PURPOSE: To investigate possible neuronal dysfunction of the thalamus in patients suffering from typical absence epilepsy, using magnetic resonance spectroscopy (MRS). Special attention was paid to levels of N-acetylaspartate (NAA) and creatine (Cr), and to the NAA/Cr ratio. METHODS: MRS was performed over the right and left thalamus in nine patients suffering from typical absence epilepsy, and in nine sex- and age-matched healthy controls. All patients and controls were examined using a standard MRS-CSI (chemical shift imaging) technique. RESULTS: Statistical analysis of the obtained data demonstrated a significantly lower thalamic NAA/Cr ratio in patients with typical absence epilepsy when compared to the healthy controls. Our MRS data showed symmetrical distribution of NAA/Cr ratio in the right and left thalamus within both the patient group and the group of healthy controls. No significant correlation between the patients' thalamic NAA/Cr values and the duration of the epilepsy or seizure frequency was revealed. CONCLUSIONS: The present MRS data clearly indicate neuronal dysfunction in the thalami of patients with typical absence epilepsy. In agreement with other recent MRS findings in different idiopathic generalized epilepsy syndromes, our results confirm the role of the thalamus as an important structure in the pathogenesis of typical absence epilepsy.

Adult↗

Early and specific expression of monocyte chemoattractant protein-1 in the thalamus induced by cortical injury.

For many years it has been known that retrograde degeneration of thalamic neurons occurs following damage to the cerebral cortex, however, the molecular mechanisms which control this process are unknown. Recent studies have demonstrated microglial activation in thalamic nuclei well before the onset of retrograde neuronal cell death. Activated monocytes and microglia synthesize factors detrimental to neuronal survival as well as phagocytose damaged and dying neurons. Our previous studies demonstrated that monocyte chemoattractant protein-1 (MCP-1), a beta chemokine which attracts cells of monocytic origin to sites of injury, is rapidly expressed in the brain following visual cortical lesions. The present study examined the expression of MCP-1 messenger RNA and protein in the thalamus following a visual cortical lesion. Aspiration lesions of visual cortex were made in adult mice. At specific times after lesion, brains were harvested and dissected into specific regions. MCP-1 message as detected using northern analysis was absent in uninjured brain, but was elevated in the ipsilateral thalamus as rapidly as 1 h following the lesion. In situ hybridization localized MCP-1 message to subpial glial cells of the lateral geniculate nucleus (LGN) of the ipsilateral thalamus after injury. ELISA showed that MCP-1 protein levels were significantly elevated in the ipsilateral thalamus at 6 h, peaked at 12 h, and remained above baseline levels for at least 1 week post lesion. In addition, anti-GFAP staining demonstrated activated astrocytes localized to the ipsilateral LGN at 24 and 72 h after injury. The early expression and regional localization of MCP-1 mRNA and protein strongly suggest that MCP-1 is a critical molecule in the regulation of thalamic retrograde neuronal degeneration.

Animals↗

Evidence for membrane remodeling in ipsilateral thalamus and amygdala following left amygdala-kindled seizures in awake rats.

We examined regional cerebral metabolic rates for glucose (rCMRglc) and brain incorporation coefficients (k*) of each of three intravenously infused fatty acid radiotracers, [9,10-(3H)]palmitate ([3H]PAM), [1-(14C)]arachidonate ([14C]AA) and [1-(14C)]docosahe-xaenoate ([14C]DHA), in awake rats fully kindled by once-daily electrical stimulation of the left amygdala. Compared with sham-stimulated animals, rCMRglc was increased bilaterally during a seizure, particularly in midbrain-brain stem regions, thalamus and basolateral nucleus of the amygdala. At 24 h and 2 weeks after a seizure, there was no significant change in k* for either [14C]AA or [14C]DHA in any brain region, whereas k* for [3H]PAM at 24 h was increased significantly (by 32-53%) ipsilateral to stimulation in regions of the amygdala and thalamus. Contralateral regions showed no significant change. Two weeks after a seizure, k* for [3H]PAM was increased in the ipsilateral lateral dorsal nucleus of the thalamus. These results argue for membrane remodeling involving phosphatidylcholine in the ipsilateral amygdala and thalamus at the completed phase of amygdala kindling. Remodeling may continue for up to 2 weeks after a seizure during the completed phase.

Amygdala↗