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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↗
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↗
PubMed1999

Organization of the basal forebrain projection to the thalamus in rats.

We have examined the patterns of projections that exist between the different nuclei of the basal forebrain (BF) and the thalamus. Injections of biotinylated dextran were made into different nuclei of the BF (i.e. substantia innominata, nucleus basalis of Meynert, vertical and horizontal limbs of the diagonal band) of Sprague-Dawley rats using stereotaxic coordinates. Our results show that all of the above-mentioned BF nuclei have projections to the thalamus and that projections from different nuclei are rather similar. The bulk of the BF afferents terminate within the intralaminar, midline and mediodorsal nuclei of the dorsal thalamus and the zona incerta and reticular nucleus of the ventral thalamus. Very few terminals are ever seen in the other nuclei of the thalamus. Thus our results indicate that the BF targets particular thalamic nuclei, thereby being in a position to influence distinct thalamo-cortical pathways.

Afferent Pathways↗
PubMed2001

Corticotropin-releasing hormone messenger RNA distribution and stress-induced activation in the thalamus.

Corticotropin-releasing hormone plays a critical role in mediating the stress response. Brain circuits hypothesized to mediate stress include the thalamus, which plays a pivotal role in distributing sensory information to cortical and subcortical structures. In situ hybridization revealed neurons containing corticotropin-releasing hormone messenger RNA in the posterior thalamic nuclear group and the central medial nucleus of the thalamus, which interfaces with the ventral posteromedial nucleus (parvicellular part). These regions are of interest because they process somatosensory and visceral information. In the first experiment, the effect of acute stress on thalamic corticotropin-releasing hormone messenger RNA levels was assessed. Rats restrained for 1 h and killed 1 h later were found to have increased corticotropin-releasing hormone messenger RNA in the posterior thalamic nuclear group. The time course of these changes was examined in a second experiment in which rats were killed immediately or 3 h after restraint. While no changes occurred in the thalamus immediately after restraint, 3 h after restraint, increases in corticotropin-releasing hormone messenger RNA occurred in both the posterior thalamic nuclear group and the central medial-ventral posteromedial nucleus (parvicellular part) of the thalamus. A different pattern of activation was observed in the paraventricular nucleus of the hypothalamus with increased corticotropin-releasing hormone messenger RNA immediately after restraint, but not 1 or 3 h later. In addition to the stress-induced changes, a prominent decrease in baseline thalamic corticotropin-releasing hormone messenger RNA was observed from 1000 to 1300 h. These results show that the thalamus contains corticotropin-releasing hormone messenger RNA that increases after restraint stress, indicating a role for thalamic corticotropin-releasing hormone systems in the stress response. Stress-induced changes in thalamic corticotropin-releasing hormone messenger RNA expression appears to be regulated differently than that in the paraventricular nucleus of the hypothalamus, and may be influenced by diurnal mechanisms.

Animals↗
PubMed2001

The efferent connections to the thalamus and brainstem of the physiologically defined eye field in the rat medial frontal cortex.

The anterograde tracer Phaseolus vulgaris leucoagglutinin (PHA-L) was injected into sites of the rat frontal eye field (FEF) located in the medial frontal cortex. After a single iontophoretic injection of PHA-L into a FEF site where intracortical microstimulation elicited eye movements, anterogradely labelled fibres and terminal-like elements were found in the thalamus in the anterior nuclei, intralaminar nuclei, lateral portion of the mediodorsal nucleus and posterior nuclear group. In the midbrain and pons, labelled fibres were located in the anterior pretectal area, Darkschewitsch nucleus, superior colliculus and dorsolateral portion of the central gray. When the tracer was injected at the FEF periphery, at a site the stimulation of which evoked both eye and whisker movements, labelling distribution in the thalamus differed from that observed after FEF injections, while a similar distribution was observed in the brainstem. In the thalamus, anterograde labelling was observed in these latter cases in the anterior nuclei, ventral nuclei, medial portion of the laterodorsal nucleus. The present findings point out that the FEF and FEF periphery are connected with numerous subcortical structures of the thalamus and brainstem. In addition, the connections of FEF and FEF periphery with the thalamus differ, whereas the midbrain and pons connections of the two subdivisions share common targets.

Animals↗
PubMed1998

A developmental study of the dopamine D2R receptors in the human basal ganglia and thalamus.

The development of the dopamine D2R receptors (D2R) in the human basal ganglia (BG) and thalamus was investigated in 25 normal brains by means of an immunohistochemical method and Western blotting. Immunoreactivity to D2R was detected in the cytoplasm and dendrites of small and large neurons in the BG and thalamus. D2R-positive neurons were clearly observed at 19 weeks of gestation (GW) in the globus pallidus and thalamus, and at 21 GW in the striatum. The number of D2R-positive neurons gradually increased and reached a peak at 27 GW in the globus pallidus, at 39 GW in the thalamus, and at 1 month of age in the striatum. The number of D2R-positive large neurons in the globus pallidus and small neurons in the striatum decreased after 1 year and about 10 years of age, respectively. Western blotting confirmed the specificity of the immunohistochemistry. Our results suggest that the D2R protein begins to be synthesized at an early fetal stage in the BG and thalamus, and the development of D2R is mostly consistent with neuronal maturation in the BG. D2R may play an important role in regulating the neuronal development of the BG. The decrease in D2R-positive neurons may be related to D2R post-transcriptional regulation.

Adolescent↗
PubMed2004

Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus.

Parcellation of the human thalamus based on cortical connectivity information inferred from non-invasive diffusion-weighted images identifies sub-regions that we have proposed correspond to nuclei. Here we test the functional and anatomical validity of this proposal by comparing data from diffusion tractography, cytoarchitecture and functional imaging. We acquired diffusion imaging data in eleven healthy subjects and performed probabilistic tractography from voxels within the thalamus. Cortical connectivity information was used to divide the thalamus into sub-regions with highest probability of connectivity to distinct cortical areas. The relative volumes of these connectivity-defined sub-regions correlate well with volumetric predictions based on a histological atlas. Previously reported centres of functional activation within the thalamus during motor or executive tasks co-localize within atlas regions showing high probabilities of connection to motor or prefrontal cortices, respectively. This work provides a powerful validation of quantitative grey matter segmentation using diffusion tractography in humans. Co-registering thalamic sub-regions from 11 healthy individuals characterizes inter-individual variation in segmentation and results in a population-based atlas of the human thalamus that can be used to assign likely anatomical labels to thalamic locations in standard brain space. This provides a tool for specific localization of functional activations or lesions to putative thalamic nuclei.

Adult↗
PubMed2003

Protein synthesis in the amygdala, but not the auditory thalamus, is required for consolidation of Pavlovian fear conditioning in rats.

The amygdala is an essential neural substrate for Pavlovian fear conditioning. Nevertheless, long-term synaptic plasticity in amygdaloid afferents, such as the auditory thalamus, may contribute to the formation of fear memories. We therefore compared the influence of protein synthesis inhibition in the amygdala and the auditory thalamus on the consolidation of Pavlovian fear conditioning in Long-Evans rats. Rats received three tone-footshock trials in a novel conditioning chamber. Immediately after fear conditioning, rats were infused intra-cranially with the protein synthesis inhibitor, anisomycin. Conditional fear to the tone and conditioning context was assessed by measuring freezing behaviour in separate retention tests conducted at least 24 h following conditioning. Post-training infusion of anisomycin into the amygdala impaired conditional freezing to both the auditory and contextual stimuli associated with footshock. In contrast, intra-thalamic infusions of anisomycin or a broad-spectrum protein kinase inhibitor [1-(5'-isoquinolinesulphonyl)-2-methylpiperazine, H7] did not affect conditional freezing during the retention tests. Pre-training intra-thalamic infusion of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (APV), which blocks synaptic transmission in the auditory thalamus, produced a selective deficit in the acquisition of auditory fear conditioning. Autoradiographic assays of cerebral [14C]-leucine incorporation revealed similar levels of protein synthesis inhibition in the amygdala and thalamus following intra-cranial anisomycin infusions. These results reveal that the establishment of long-term fear memories requires protein synthesis in the amygdala, but not the thalamus, after auditory fear conditioning. Forms of synaptic plasticity that depend on protein synthesis, such as long-term potentiation, are likely candidates for the encoding and long-term storage of fear memories in the amygdala.

Amygdala↗
PubMed1993

Amino acid levels and gamma-aminobutyric acidA receptors in rat neostriatum, cortex, and thalamus after neonatal 6-hydroxydopamine lesion.

The amino acid gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in brain, and GABAergic neurons have been proposed to play a major role in basal ganglia physiology. In the neostriatum (caudate putamen), medium-sized aspiny interneurons, as well as neostriatal output neurons that project to several brain regions, use GABA as their neurotransmitter. Dopamine fibers arising from the substantia nigra represent a major input to the neostriatum where, besides their classic neurotransmitter role, they are seemingly involved in the regulation of amino acid neurotransmitter release. To further characterize the nature of some of the amino acid/dopamine interactions, selective dopaminergic deafferentations were produced in neonatal rats (3 days postnatal) by intraventricular administration of the neurotoxin 6-hydroxydopamine (6-OHDA); the noradrenergic neurons were protected by prior administration of desmethylimipramine. After a 3-month survival, levels of catecholamines, indoleamines, and amino acids were determined in cingulate cortex, thalamus, and neostriatum. In addition, GABAA receptors were measured in membrane preparations from these three regions, using the specific agonist [3H]muscimol. In the 6-hydroxydopamine-lesioned rats, levels of dopamine and its metabolites homovanillic acid, 3,4-dihydroxyphenylacetic acid, and 3-methoxytyramine were decreased, as expected, in cortex and neostriatum, but remained unmodified in thalamus. In all three regions, serotonin content was increased; its metabolite, 5-hydroxyindole-3-acetic acid, was also elevated, but only in cortex and neostriatum. The levels of GABA were increased in neostriatum and thalamus, but remained unmodified in cortex. Glycine was increased in all three regions examined. There were also increases of phosphatidylethanolamine and serine in thalamus, and of aspartic acid and alanine in neostriatum. The density of GABAA binding sites was increased in neostriatum, but remained unchanged in cortex and thalamus. The changes in amino acid levels and [3H]muscimol binding sites induced by a neonatal 6-hydroxydopamine treatment differ from those found after similar lesions in adult animals, possibly because of the plastic and synaptic rearrangements that can still occur during early postnatal development. The present results also demonstrate that adaptations occur in response to a dopaminergic deafferentation at an early age and that these exhibit a regional specificity.

Amino Acids↗