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PubMed1987

Distributions of certain neuropeptides in the primate thalamus.

The distributions of fibers and terminals immunoreactive for somatostatin (SRIF), neuropeptide Y (NPY), substance P (SP) and cholecystokinin octapeptide (CCK), were studied in the diencephalon of cynomolgus monkeys. Immunoreactivity for all 4 peptides is found in extrinsic afferent fibers innervating the dorsal thalamus, ventral thalamus and epithalamus. The distributions of such fibers are more extensive than previously described and include many relay nuclei in their zones of terminations. SP fibers are particularly concentrated in the ventral posteromedial nucleus. All peptides are especially concentrated in fibers in the intralaminar and reticular nuclei. Afferent fibers immunoreactive for each of the 4 peptides approach the thalamus by two pathways. An anterior route is formed by the classical periventricular system ascending from the hypothalamus to the epithalamus. A posterior pathway ascends in the lateral midbrain tegmentum and provides innervation to posterior, intralaminar, and many relay nuclei, plus the ventral thalamus. A basal forebrain pathway, containing SRIF and NPY immunoreactive fibers, enters the thalamus in association with the ansa lenticularis and SP fibers also ascend from the substantia nigra.

Animals↗

PubMed1991

Evidence for a critical role of GABAergic transmission within the thalamus in the genesis and control of absence seizures in the rat.

The involvement of GABAergic transmission within the thalamus in the generation and control of spike and wave discharges (SWD) in generalized non-convulsive or absence epilepsy was studied in rats with spontaneous SWD and in non-epileptic rats. In epileptic rats, bilateral injections of gamma-vinyl GABA (GVG, 10 micrograms/side) or muscimol (10 ng/side) into the medial part of the ventral lateral thalamus, i.e. the specific relay nuclei, significantly increased spontaneous cortical SWD whereas similar injections into the most lateral part of the thalamus, i.e. the area of the reticular nuclei, significantly suppressed these seizures. Injections of GVG (20 micrograms) or muscimol (20 ng) into the midline thalamus had no direct effect on the spontaneous SWD. In non-epileptic rats, injections of GVG (25 micrograms/side) or muscimol (100 ng/side) into the thalamic relay nuclei produced short SWD on the cortical EEG. These results suggest that GABAergic neurons in the reticular nuclei and their projections to the specific relay nuclei of the thalamus are involved in the elicitation and control of generalized non-convulsive seizures.

Aminocaproates↗

PubMed1993

Muscarinic and nicotinic receptor changes in the cortex and thalamus of brains of chronic alcoholics.

The cholinergic system was studied in the cortical and thalamic brain tissues obtained at autopsy from 21 chronic alcoholics and 20 controls. The age related decrease in choline acetyltransferase (ChAT) activity observed in the thalamus of control brains was not found in the corresponding brain areas of chronic alcoholics. A significant decrease in the number of muscarinic receptor binding sites was observed with age in the frontal cortex of both controls and chronic alcoholics when analysed with the nonselective muscarinic antagonist [3H]quinuclidinyl benzilate ([3H]QNB). A significant increase in the number of muscarinic receptor binding sites was observed in the thalamus of controls but not in chronic alcoholics. When the subjects were divided into young (19-57) years, and old (59-84 years) chronic alcoholics marked losses in the total number of muscarinic receptors as well as M1 and M2 receptor subtypes were found in the thalamus of the old group of alcoholics compared to age-matched controls. A coupling of muscarinic receptors to G proteins was observed in thalamic tissues from both controls and chronic alcoholics. Guanylyl-imidodiphosphate (Gpp(NH)p) induced a steepening and rightward shift of the carbachol/[3H]QNB displacement curves performed in membrane preparations of the thalamus from both controls and chronic alcoholics. The number of high affinity nicotinic binding sites in the frontal cortex and thalamus did not differ significantly between controls and chronic alcoholics.

Adult↗

PubMed1991

Postnatal development of calbindin and parvalbumin immunoreactivity in the thalamus of the rat.

The maturation of the calcium binding proteins calbindin-D28k (CB) and parvalbumin (PV) during the first 3 postnatal weeks was studied in the rat thalamus using immunohistochemistry. These two proteins display a non-homogeneous distribution in the adult thalamus. In the rat, CB is mainly localized in the neurons and neuropil of the thalamic midline, intralaminar, and ventromedial nuclei, as well as in the posterior complex. At birth, CB-immunoreactive cell bodies were evident in thalamic midline structures, and especially in the nucleus reuniens. The number of thalamic CB-positive cell bodies, as well as the intensity of the neuropil immunostaining, increased progressively in the first postnatal weeks. This quantitative increase was first apparent in the midline structures and then in the other thalamic territories which are CB-positive in adulthood, and followed a mediolateral gradient. The mature pattern was achieved by the end of the third postnatal week. In the adult rat thalamus the neurons of the reticular nucleus display PV-immunostaining and PV-positive fibers densely innervate most of the dorsal thalamic domains. PV-immunoreactivity was clearly evident at birth in the cell bodies of the reticular nucleus. The density of PV-containing fibers increased progressively after birth in the dorsal thalamus, with a lateromedial gradient. At the end of the third postnatal week the ventroposterior (VP) complex appeared heavily innervated by PV-positive fibers, whose density in more medial structures was still lower than in the adult thalamus. A transient hyperinnervation of PV-immunoreactive fibers, displaying a dishomogenous organization in distinct segments, was observed in VP, and especially in the ventroposteromedial nucleus, during the second postnatal week. Altogether these findings indicate that the maturation of CB and PV requires postnatally a relatively prolonged period of time. The possible involvement of these proteins in different functional aspects of thalamic neuronal maturation is discussed.

Animals↗

PubMed1992

Slowing of the dominant occipital rhythm in electroencephalogram is associated with low concentration of noradrenaline in the thalamus in patients with Alzheimer's disease.

The thalamus is involved in the regulation of the neocortical rhythmicity reflected in EEG as the alpha rhythm. Recent evidence suggests that the thalamus is affected in Alzheimer's disease (AD). We studied the relationship between the dominant occipital rhythm of the lifetime EEG and the choline acetyltransferase activity (ChAT) and monoamine concentrations in the postmortem thalamus of 20 histologically verified AD patients. The AD patients were divided into 3 groups (5-6 Hz, 7 Hz and 8-9 Hz) according to the frequency of the dominant occipital rhythm (FOC). Noradrenaline (NA) concentrations were significantly lower for the 5-6 Hz and 7 Hz subgroups as compared to the 8-9 Hz subgroup. The NA content of the thalamus correlated significantly with the FOC (r = 0.46, P = 0.04). The ChAT activity or concentrations of dopamine or serotonin did not correlate with the FOC or differ across the AD subgroups. The results suggests that the noradrenergic deficit of the thalamus may contribute to slowing of the dominant occipital rhythm in AD.

Aged↗

PubMed1983

Long collateral branches of substantia nigra pars reticulata axons to thalamus, superior colliculus and reticular formation in monkey and cat. Multiple retrograde neuronal labeling with fluorescent dyes.

In order to gain some impressions about the degree to which individual neurons of the pars reticulata of the substantia nigra send long collateral branches to more than one of its three major targets (thalamus, superior colliculus, reticular formation), two, or all three targets were injected with fluorescent dyes (Evan's blue, granular blue, nuclear yellow, propidium iodide) in six squirrel monkeys and four cats. The best results were obtained in the monkey brain with injections of Evan's blue in the thalamus, granular blue in the colliculus and nuclear yellow in the reticular formation. Whereas nigrothalamic and nigroreticular neurons are numerous and widely scattered throughout all parts of the pars reticulata, cells projecting only to the superior colliculus are fewer in number and restricted to a rostral-lateral zone. These results are consistent with earlier data obtained with the horseradish peroxidase method. Although double-labeled cells with projections to both the thalamus and reticular formation occur throughout the pars reticulata, such cells are somewhat more abundant at caudal levels of the nucleus. Cells containing dyes from both the superior colliculus and reticular formation are less common and restricted to the lateral part of the pars reticulata. A small number of cells near the rostral pole of the pars reticulata contain dye from both the tectal and thalamic injection. Typically, less than two dozen cells in any case can be confidently identified as containing all three dyes and these cells are located in the rostrolateral half of the pars reticulata. Fewer than 20% of the labeled nigral cells contain more than one dye. In the cat, thalamic injection of granular blue and tectal injection of nuclear yellow indicate that most nigrotectal cells are located in the middle of the mediolateral expanse of the pars reticulata in its rostral half. Nigrothalamic cells flank the nigrotectal group medially, laterally and caudally. Where these groups border one another, several cells contain both dyes indicating that they project to both the thalamus and colliculus. In both the cats and monkeys, a less extensive cell-labeling occurs in the contralateral nigra with a pattern similar to that in the ipsilateral substantia nigra. The results indicate that several neurons of the substantia nigra's pars reticulata send long collateral branches to two or even all three of the major targets. Many reticulata cells, however, appear to project either to the thalamus, or to the superior colliculus or to the reticular formation.

Animals↗

PubMed1987

Quantitative evaluation of crossed and uncrossed projections from basal ganglia and cerebellum to the cat thalamus.

Quantitative and qualitative analysis of crossed vs uncrossed projections from the substantia nigra, entopeduncular nucleus and individual cerebellar nuclei to the thalamus was undertaken in nine adult cats using retrograde labeling with horseradish peroxidase and fluorescent dyes. The results indicate that about 90% of entopeduncular nucleus neurons and 50% of substantia nigra neurons give rise to ipsilateral projections to the thalamus whereas the contralateral component of these projections originates from about 10 and 7% neurons of entopeduncular nucleus and substantia nigra, respectively. Some of the fibers constituting the contralateral component are represented by branching axon collaterals of the neurons projecting ipsilaterally. In the basal ganglia thalamic projection, its minor component (contralateral) targets the ventral anterior and ventral medial nuclei the same as its major component (ipsilateral). However, some preferential distribution of the contralateral projections to the ventral medial nucleus appears to exist. In regard to the cerebellothalamic projections it was found that about 90% of neurons located in the dentate and interpositus nuclei and 50% of neurons in the fastigial nucleus project to the contralateral thalamus while 16% of dentate nucleus neurons and 40% of fastigial nucleus neurons give rise to the ipsilateral cerebellothalamic projections. A considerable number of ipsilateral cerebellothalamic fibers are represented by divergent axon collaterals of the same neurons projecting to the contralateral thalamus. The cerebellothalamic projections from all cerebellar nuclei including the fastigial nucleus are targeted primarily to the ventral lateral nucleus both contra- and ipsilaterally. The ventral medial nucleus receives bilateral input from the fastigial nucleus which originates from about one quarter of the thalamus projecting neurons in this nucleus. Of all other cerebellar nuclei only the dentate nucleus projects to the ventral medial nucleus and this projection is exclusively contralateral.

Animals↗

PubMed1991

Neurotransmitter amino acid levels in rat thalamus and cerebral cortex after cerebellectomy.

Glutamate, aspartate, GABA, glycine and taurine levels have been measured in rat thalamus and in cerebral cortex at different time intervals (3rd, 7th, 15th, 30th day) after cerebellectomy. A decrease in glutamate, aspartate and GABA was detected at the 7th day after cerebellectomy in the thalamus and at the 15th day in the cerebral cortex; at the 30th day after cerebellectomy the levels of these amino acids in the thalamus and in the cerebral cortex were observed to have recovered to control values. No statistically significant difference in glycine and taurine levels in the thalamus and in the cerebral cortex after cerebellectomy could be seen. These results show that the functional recovery process after cerebellar injury is associated with a complex modification of amino acid levels in thalamus and in cerebral cortex.

Amino Acids↗

PubMed2004

Necrosis, apoptosis and hybrid death in the cortex and thalamus after barrel cortex ischemia in rats.

Focal ischemia in the cerebral cortex results in acute and delayed cell death in the ischemic cortex and non-ischemic thalamus. We examined the hypothesis that neurons in ischemic and non-ischemic regions died from different mechanisms; specifically, we tested whether a mixed form of cell death containing both necrotic and apoptotic changes could be identified in individual cells. Focal barrel cortex ischemia in rats was induced by occlusion of small branches of the middle cerebral artery (MCA) corresponding to the barrel cortex, local blood flow was measured by quantitative autoradiography. Cell death was visualized by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin-eosin (H&E) staining, the terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL), and caspase-3 staining 1 to 10 days after the ischemia. Electron microscopy was used for ultrastructural examination. Cell death occurred in the ipsilateral cortex 24 h after ischemia, followed by selective neuronal death in the ventrobasal (VB) thalamus 3 days later. TUNEL positive neurons were found in these two regions, but with striking morphological differences, designated as type I and type II TUNEL positive cells. The type I TUNEL positive cells in the ischemic cortex underwent necrotic changes. The type II TUNEL positive cells in the thalamus and the cortex penumbra region represented a hybrid death, featured by concurrent apoptotic and necrotic alterations in individual cells, including marked caspase-3 activation, nuclear condensation/fragmentation, but with swollen cytoplasm, damaged organelles and deteriorated membranes. Cell death in the thalamus and the cortex penumbra were attenuated by delayed administration of the caspase inhibitor benzyloxycarbonyl-Val-Ala-Asp fluoromethylketone (Z-VAD-FMK). Our data suggest that TUNEL staining should be evaluated with morphological changes, the hybrid death but not typical apoptosis occurs in the penumbra region and non-ischemic thalamus after cerebral ischemia.

Amino Acid Chloromethyl Ketones↗

PubMed2005

Histamine H(1) and H(3) receptors in the rat thalamus and their modulation after systemic kainic acid administration.

In rat thalamus, histamine H(1) receptor and isoforms of H(3) receptor were expressed predominantly in the midline and intralaminar areas. Correspondingly, higher H(1) and H(3) receptor binding was also detected in these areas. All isoforms of H(3) receptor were expressed in several thalamic nuclei, but there were minor differences between their expression patterns. H(1) mRNA expression was high in the ventral thalamus, but the H(1) binding level was low in these areas. Since increased brain histamine appears to have an antiepileptic effect through the H(1) receptor activity, kainic acid (KA)-induced status epilepticus in rat was used to study modulation of H(1) and H(3) receptors in the thalamus following seizures. After systemic KA administration, transient decreases in mRNA expression of H(1) receptor and H(3) receptor isoforms with full-length third intracellular loops were seen in the midline areas and the H(1) receptor mRNA expression also decreased in the ventral thalamus. After 1 week, a robust increase in mRNA expression of H(3) receptor isoforms with a full-length third intracellular loop was found in the ventral posterior, posterior, and geniculate nuclei. The changes indicate a modulatory role of H(3) receptor in the sensory and motor relays, and might be involved in possible neuroprotective and compensatory mechanisms after KA administration. However, short-term increases in the H(3) receptor binding appeared earlier (72 h) than the increases of H(3) mRNA expression (1-4 w). The elevations in H(3) binding were evident in the intralaminar area, laterodorsal, lateral posterior, posterior and geniculate nuclei, and were likely to be related to the cortical and subcortical inputs to thalamus.

Animals↗

PubMed2005

In cat four times as many lamina I neurons project to the parabrachial nuclei and twice as many to the periaqueductal gray as to the thalamus.

The spinothalamic tract, and especially its fibers originating in lamina I, is the best known pathway for transmission of nociceptive information. On the other hand, different studies have suggested that more lamina I cells project to the parabrachial nuclei (PBN) and periaqueductal gray (PAG) than to the thalamus. The exact ratio of the number of lamina I projections to PBN, PAG and thalamus is not known, because comprehensive studies examining these three projections from all spinal segments, using the same tracers and counting methods, do not exist. In the present study, the differences in number and distribution of retrogradely labeled lamina I cells in each segment of the cat spinal cord (C1-Coc2) were determined after large wheat germ agglutinin-conjugated horseradish peroxidase (WGA-HRP) injections in either PBN, PAG or thalamus. We estimate that approximately 6000 lamina I cells project to PBN, 3000 to PAG and less than 1500 to the thalamus. Of the lamina I cells projecting to thalamus or PAG more than 80%, and of the lamina I-PBN cells approximately 60%, were located on the contralateral side. In all cases, most labeled lamina I cells were found in the upper two cervical segments and in the cervical and lumbar enlargements.

Animals↗

PubMed2005

Developmental changes in the expression of growth-associated protein-43 mRNA in the monkey thalamus: northern blot and in situ hybridization studies.

The expression of growth-associated protein-43 has been related to axonal elongation and synaptic sprouting. Using the Northern blot analysis, we investigated the developmental changes of growth-associated protein-43 mRNA in the thalamus of macaque monkeys. The amount of growth-associated protein-43 mRNA was high at embryonic day 125, and decreased at postnatal day 1. It increased again at postnatal day 8, reached its peak value at postnatal days 50-70, and then decreased gradually until postnatal year 1. We previously reported that the amount of growth-associated protein-43 mRNA in the cerebral cortex decreased roughly exponentially during perinatal and postnatal periods and that it approached the asymptote by postnatal day 70 [Oishi T, Higo N, Umino Y, Matsuda K, Hayashi M (1998) Development of GAP-43 mRNA in the macaque cerebral cortex. Dev Brain Res 109:87-97]. The present findings may indicate that extensive synaptic growth of thalamic neurons continues even after that of cortical neurons has finished. We then performed in situ hybridization to investigate whether the expression level of growth-associated protein-43 mRNA was different among various thalamic nuclei. In the infant thalamus (postnatal days 70-90), moderate to intense expression of growth-associated protein-43 mRNA was detected in all thalamic nuclei. Quantitative analysis in the infant thalamus indicated that the expression levels were different between the nuclear groups that are defined by the origin of their afferents. The expression in the first order nuclei, which receive their primary afferent fibers from ascending pathways [Guillery RW (1995) Anatomical evidence concerning the role of the thalamus in corticocortical communication: a brief review. J Anat 187 (Pt 3):583-592], was significantly higher than that in the higher order nuclei. While moderate expression was also detected in the adult dorsal thalamus, the expression in the first order nuclei was almost the same as that in the higher order nuclei. Thus, the in situ hybridization experiments indicated that the transient postnatal increase in the amount of growth-associated protein-43 mRNA, which was shown by the Northern blot analysis, was mainly attributed to enhanced expression in the first order nuclei during the postnatal period. This may be a molecular basis for environmentally induced modification of thalamocortical synapses.

Animals↗

PubMed1999

Reduction of the small synaptic vesicle protein synaptophysin but not the large dense core chromogranins in the left thalamus of subjects with schizophrenia.

BACKGROUND: It has been hypothesized that a lesion in the neuronal circuits of thalamus might contribute to the symptoms in schizophrenia. It has also been suggested that impaired synaptic transmission is an important component of the pathophysiology of schizophrenia. In the present study we assess the synaptic integrity of thalamus by means of examining the protein levels of: (1) synaptophysin, a membrane bound protein of small synaptic vesicles, and (2) chromogranins, a family of soluble secretory proteins stored and released from the secretory large dense-core vesicles. METHODS: The brains of 9 patients with schizophrenia and 9 age-matched control subjects were studied. The levels of synaptophysin and chromogranins were measured by radioimmunoassays. RESULTS: The amount of synaptophysin in the left thalamus was significantly decreased (p = .036) in the schizophrenic group (2655 +/- 605 nmol synaptophysin/mg total protein) compared to the control group (3248 +/- 827 nmol synaptophysin/mg total protein). There were no differences between the groups in the levels of chromogranins, nor in the levels of synaptophysin of the right thalamus. CONCLUSIONS: These findings indicate defect synaptic function in the left thalamus of patients with schizophrenia. This may be the cause of a reduction of synaptic terminals or a defect limited to certain structures of the synapse, namely the small presynaptic vesicles.

Aged↗

PubMed2001

Agonist-induced mu opioid receptor phosphorylation and functional desensitization in rat thalamus.

By metabolically labeling tissue slices from striatum and thalamus with [32P]orthophosphoric acid and immunoprecipitating the receptor with mu receptor-specific antiserum, we found that the endogenous mu receptor in the brain tissue did undergo phosphorylation. The phosphorylation occurred at basal level (no drug treatment) and was enhanced with DAMGO-treatment. The enhancement of the phosphorylation was blocked by naloxone. Morphine stimulation also increased the phosphorylation, but the amount of enhancement was less than that caused by DAMGO-treatment. Mu receptor phosphorylation in the thalamus was much greater than the striatum, while no phosphorylation of the mu receptor in the cerebellum was detected, even with DAMGO treatment. The extent of mu receptor phosphorylation identified in the thalamus, striatum and cerebellum is consistent with the previous studies of mu receptor distribution. The time course and dose-response studies demonstrated that mu receptor phosphorylation was a rapid event, exhibited a positive dose-dependent response, and was similar to that observed in the cloned mu receptor in CHO cells. Furthermore, we correlated the change of mu receptor phosphorylation with the desensitization of the mu receptor function, specifically, inhibition of adenylyl cyclase activity in the thalamus of morphine-tolerant rats. We found that in the thalamus of rats chronically treated with morphine, the enhancement of mu receptor phosphorylation in basal and DAMGO-treated samples paralleled the desensitization of DAMGO-mediated inhibition of adenylyl cyclase. Our results suggest that mu receptor phosphorylation in vivo may play an important role in the modulation of mu receptor function following both acute exposure to morphine and during the development of morphine tolerance.

Adenylyl Cyclases↗

PubMed1997

Three-dimensional mapping of norepinephrine and serotonin in human thalamus.

Detailed quantitative information on catecholamines and 5-hydroxytryptamine (serotonin) in the human thalamus is much needed because of increasing interest in norepinephrine and serotonin as modulators of thalamic behavioral state control and overall information processing. This study provides three-dimensional distribution patterns of these monoamines in postmortem thalami from 13 normal subjects (no known neurological or psychiatric histories). The patterns come from a relatively fine-grained grid mapping procedure on successive coronal sections. Samples were analyzed by high performance liquid chromatography with electrochemical detection. The highest endogenous concentrations of norepinephrine are found in a ventromedial core that includes a number of the medial and intralaminar sub-nuclei but extends only slightly into the sensory regions of the lateral tier. The posterior portion of the thalamus, the pulvinar, contains low levels of norepinephrine. The distribution of 5-hydroxytryptamine is quite similar to that of norepinephrine in the rostral two-thirds of thalamus; however, in the pulvinar region, levels of serotonin are considerably increased and differ markedly between individual thalami. The study provides the first definitive mapping of serotonin levels in human thalamus. Consistent with many animal studies, there is no evidence for major dopaminergic innervation of human thalamus. By emphasizing the pattern distribution of the monoamines rather than the absolute values, it can be shown that the ambiguities of postmortem degradation frequently associated with biochemical assays are largely avoided. The terminal field distribution of norepinephrine is an essentially constant neurochemical signature in all thalami examined. The utility of the biochemical grid mapping procedure may be especially significant in terms of matching with data from functional neuroimaging techniques.

Brain↗

PubMed1999

Distribution of GABA(B) binding sites in the thalamus and basal ganglia of the rhesus monkey (Macaca mulatta).

The regional distribution of GABA(B) receptor binding sites in the thalamus and basal ganglia of rhesus monkey has been determined by receptor autoradiography using the agonist ligand, [3H]-GABA. Whilst binding sites were evident throughout the thalamus, the internuclear differences in the Bmax were up to 10-fold. In the basal ganglia the binding density was on average lower than in the thalamus. The highest number of binding sites was in striatum followed closely by substantia nigra. In both the thalamus and basal ganglia, the binding density was higher than previously described in the rat. Although our results do not allow us to differentiate between presynaptic and postsynaptic locations of GABA(B) sites we conclude that with a few exceptions the distribution pattern of GABA(B) binding sites in the monkey thalamus appears to correlate with the known innervation from the NRT.

Animals↗

PubMed2005

Pain and the primate thalamus.

Noxious stimuli that are perceived as painful, are conveyed to the thalamus by the spinothalamic tract (STT) and the spinotrigeminothalamic tracts (vSTT), arising from the dorsal horn of the spinal cord and medulla, respectively. Most investigators have concluded that the thalamic terminus of these pathways include several nuclei of the somatosensory and intralaminar thalamus. Non-noxious stimuli are carried by the dorsal column/medial lemniscal or the trigeminothalamic pathways which terminate in much more restricted regions of the thalamus than do the STT and vSTT systems. Lesions of components of the somatosensory pathways result in profound changes in the circuitry of the recipient thalamic nuclei. Not only are there the expected losses of the injured axons and their synaptic terminations, but there is also a marked reduction of the intrinsic GABAergic circuitry, even though the GABAergic neurons contributing to the circuitry have not been injured directly by lesions of the afferent pathways. Such changes in the inhibitory circuitry observed in experimental animals may explain the abnormal bursting behavior of thalamic neurons found in patients with central deafferentation pain syndromes. One potential approach to treating chronic pain would be to selectively remove the neurons of the superficial dorsal horn (lamina I) that specifically respond to noxious stimuli (NS neurons). A toxin has been developed (SSP saporin) that binds to the substance P receptor of NS neurons, is internalized by the neuron and kills the cell. SSP saporin has been shown to be effective in rats, and we have recently demonstrated that it effectively causes lesions in NS neurons of the lumbar spinal cord in the monkey and reduces the animals' response to noxious cutaneous stimuli. The SSP-saporin administration to the lumbar spinal cord destroys a relatively small number of the total neurons that project into the somatosensory thalamus and does not lead to demonstrable changes in the inhibitory circuitry of the thalamus, in contrast to lesions of major pathways that lead to reductions in the thalamic inhibitory circuitry.

Animals↗

PubMed1998

The role of the gustatory thalamus in taste-guided behavior.

Gustatory thalamus is the functional name for the parvicellular region of the ventroposteromedial nucleus of the thalamus. It is the penultimate nucleus in the thalamocortical pathway of the central gustatory system. Early research encouraged the view that the gustatory thalamus was important for taste detection and recognition. Consistent with this analysis, lesions of the area were found to induce profound deficits of innate taste preferences and aversions, salt appetite, and conditioned taste aversions (CTAs). More recent research using discrete lesions placed with electrophysiological guidance has, however, demonstrated that these deficits were due to damage to structures outside of, rather than within, the boundaries of the gustatory thalamus. In fact, the new data show that the gustatory thalamus is not essential for taste detection, sodium appetite, or CTA learning, but is critical for the preparatory (i.e. food-seeking) rather than the consummatory (i.e. food-eating) aspects of taste-guided behavior.

Animals↗