PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “LIMBIC SYSTEM”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 217 records · Page 12Linked to original sources
PubMed1996

A subclass of GABAA/benzodiazepine receptor exclusively localized in the limbic system.

An in vivo saturation study using 11C-labelled Ro15-4513 with high specific radioactivity (> 70 GBq mumol-1) revealed the presence of very high-affinity and high-affinity binding sites (Kd values in the amygdala approximately 0.4 and 18.7 nM, respectively) in the gamma-aminobutyric acid type A/benzodiazepine (GABAA/BZ) receptor in the living monkey brain. Subtraction of an image obtained using [11C]Ro15-4513 with low specific radioactivity from an image obtained by that with high specific radioactivity, both of which were scanned with a high spatial resolution positron emission tomography camera, demonstrated that the very high-affinity sites are exclusively localized in the limbic system, such as in the amygdala, hippocampus, anterior cingulate, septum, nucleus accumbens and insular cortex. The localization of the very high-affinity binding sites, which may be derived from a subclass of central GABAA/BZ receptors, might account for the anxiolytic effect of BZ analogues.

Affinity Labels↗
PubMed2001

Estrogen synthetase (aromatase) immunohistochemistry reveals concordance between avian and rodent limbic systems and hypothalami.

During amniote evolution, an early divergence occurred about 300 million years ago between the reptilian lines leading to the appearance of birds (anapsids) and mammals (synapsids). The different functional requirements of these vertebrate groups have involved divergent evolution of their brains. Even superficial examination reveals major anatomical differences between mammalian and avian brains, such as extensive development of the optic lobes and cerebellum in birds and a highly developed cortex in mammals. It has been nearly impossible to identify avian homologs of some mammalian brain regions by standard morphological criteria. This has long frustrated efforts at clarifying hypotheses regarding the anatomical location, field size, and regulation of brain functions shared between these two classes, despite the certainty that the principles of neurobiology apply equally at the cellular level in both groups. In an effort to remove this barrier, we have sought markers of common function that despite apparent anatomical dissimilarity, can allow recognition of homologous brain structures. We illustrate here how comparative analysis of the distribution of the steroid-metabolizing enzyme estrogen synthetase (aromatase) may help to understand the differences and similarities in the limbic system and hypothalamus of birds and mammals.

Animals↗
PubMed1992

Immunohistochemical localization of the D1 dopamine receptor in rat brain reveals its axonal transport, pre- and postsynaptic localization, and prevalence in the basal ganglia, limbic system, and thalamic reticular nucleus.

D1 dopamine receptor localization was examined by immunohistochemistry using a polyclonal anti-peptide antibody which (i) immunoprecipitated a protein fragment encoded by a D1 receptor cDNA and (ii) on Western blots of solubilized striatal and hippocampal membranes recognized two proteins of approximately 50 kDa and 75 kDa, corresponding to reported sizes of D1 receptor proteins. Immunoreactivity overlapped with dopamine-containing pathways, patterns of D1 receptor binding, and mRNA expression. Staining was concentrated in prefrontal, cingulate, parietal, piriform, entorhinal, and hippocampal cortical areas and subcortically in the basal ganglia, amygdala, septal area, substantia inominata, thalamus, hypothalamus, and neurohypophysis. Prominent labeling was seen in the thalamic reticular nucleus, a region known to integrate ascending basal forebrain inputs with thalamocortical and corticothalamic pathways and in fiber bundles interconnecting limbic areas. In striatal neuropil, staining appeared in spines (heads and necks), at postsynaptic sites in dendrites, and in axon terminals; in the pars reticulata of the substantia nigra, labeling was prevalent in myelinated and unmyelinated axons and dendrites. These data provide direct evidence for the regional and subcellular distribution of D1 receptor protein in the brain and for its pre- and postsynaptic localization in the basal ganglia. The prominent immunoreactivity seen in the limbic system and thalamic reticular nucleus supports an important role for this receptor subtype in mediating integrative processes involved with learning, memory, and cognition.

Animals↗
PubMed2000

In vivo NMDA/dopamine interaction resulting in Fos production in the limbic system and basal ganglia of the mouse brain.

Glutamatergic and dopaminergic effects on molecular processes have been extensively investigated in the basal ganglia. It has been demonstrated that NMDA and dopamine D(1) and D(2) receptors interact in the regulation of signal transduction and induction of transcription factors. In the present experiments, NMDA/dopamine interactions were investigated in the normosensitive caudate nucleus, hippocampus and amygdala by monitoring Fos production. We demonstrated that NMDA and the D(1) receptor agonist SKF 38393 triggered Fos levels in a distinct, non-overlapping and region-specific pattern. NMDA injected intraperitoneally (i.p.) elevated Fos levels in all hippocampal subfields and the central amygdala, whereas SKF 38393 triggered Fos production in basomedial, cortical, medial amygdala and caudate nucleus. The NMDA receptor antagonist CGS 19755 prevented NMDA- and SKF 38393-triggered Fos production in all investigated brain areas. Similarly, the D(1) receptor antagonist SCH 23390 inhibited the effects produced by SKF 38393 or NMDA. The D(2) receptor antagonist sulpiride exerted synergistic and antagonistic effects on NMDA- and SKF 38393-triggered Fos production, in a region specific manner. These data suggest that NMDA and dopamine receptors regulate Fos production within the limbic system and basal ganglia through regionally differentiated but interdependent actions.

Animals↗
PubMed1987

Deviations in brain development due to caloric undernutrition and scope of their prevention by rehabilitation: alterations in the power spectra of the EEG of areas of the neocortex and limbic system.

Wistar rats underwent caloric undernutrition so as to produce undernourished pups (F1, both male and female), which were put on a reduced diet throughout life, causing deficits in body weight of 40-70%, and in brain weight of 14-20% by adulthood. These chronic undernourished rats were mated and their progeny (F2), which had suffered gestational and postnatal undernutrition, were undernourished, like their parents, throughout life until the moment of use in this study. At this degree of chronic undernutrition, rats do not appear to be sick or morbid, but only small-for-age, they are active and can reproduce. The computer-generated power spectra of the EEG of two neocortical areas (visual and motor) and of 3 regions of the limbic system (cingulate, hippocampus and olfactory bulb) of the chronically undernourished pups were obtained at different ages from birth to adulthood, and compared with the normal ontogenetic patterns of corresponding areas obtained from age-matched controls. In another group of rats, the undernutrition was imposed on normal pups from the day of weaning (21st day), i.e., after the major part of the brain growth spurt is over. Finally, the effect of restituting normal rehabilitatory nutrition from the day of weaning on the chronic group was also studied. The results show that all brain regions studied were affected by the chronic caloric undernutrition. The deviations from the normal consist of: (1) an initial lag or delay in the development of the EEG amplitude and activity by several days, (2) a later development of an abnormally high amplitude or power in the EEG power spectra by about the weaning age, and (3) an imbalance in the occurrence of the characteristics of the EEG of the respective areas of the brain (the low and high frequency spindles of slow sleep, the slow and fast theta activities of paradoxical sleep of the hippocampus, the delta rhythm, etc.). While the chronic undernutrition was continuing there was also a certain degree of spontaneous reduction in the magnitude of abnormality after about 80 days of age, instead of worsening with age, perhaps due to an intrinsic adaptational readjustment to the stress of the nutritional deprivation. The results reveal a variation in the susceptibility of development to these abnormalities. Typical examples of the range of variation of the effects are presented in the results showing that there can be nearly normal EEG patterns in some undernourished subjects (about 14-22%), and also that there can be abnormal EEG power spectra in a proportion of normals (up to about 20%).(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed2000

Developmental switch in the expression of GABA(A) receptor subunits alpha(1) and alpha(2) in the hypothalamus and limbic system of the rat.

The GABA(A) receptor is a pentameric ligand gated ion channel complex assembled from a family of at least 17 different subunits encoded by distinct genes. Two subunits, alpha(1) and alpha(2), exhibit age dependent expression throughout several areas of the brain. In general, the density of immunoreactive product for alpha(1) is greatest in the adult brain, while alpha(2) is highest in younger tissue. Since the developmental switch in alpha(1) and alpha(2) coincides with the end of the sensitive period for steroid-mediated sexual differentiation of the brain, we hypothesized that GABA(A) receptor subunit expression may be involved in this process. We have examined the age-dependent expression of alpha(1) and alpha(2) in discrete regions of the hypothalamus and limbic system of males and females. While we did not detect any dramatic sex differences in alpha(1) or alpha(2) immunoreactive density, each region exhibited a unique developmental profile. In the ventromedial nucleus of neonatal animals immunoreactivity is highest for alpha(1), while in the adult the signal for alpha(2) is greater; the opposite of that observed in the ventrolateral thalamus. There is no age dependent change for alpha(1) in the preoptic area, while alpha(2) shows a small, but significant increase. Immunoreactive densities for both subunits increase in the arcuate nucleus and the hippocampus, but decrease in the lateral amygdala. We conclude that these regional differences in subunit expression across development determine individual characteristics of brain areas and may play a role in establishing unique physiological responses to GABA.

Aging↗
PubMed2000

Activation of fronto-limbic system in the human brain by cigarette smoking: evaluated by a CBF measurement.

Nicotine produces profound behavioral effects in humans, but little is known about the sites of its action. There is a hypothesis that frontal lobe and limbic/cingulate cortical structures might be the sites. In this study, we examined the effects of cigarette smoking on feeling and cerebral blood flow (CBF) in human subjects. Young and healthy 9 cigarette smokers (all males, 24-33 years, average, 26.4) were included. After prohibiting them from smoking for 15 hours, CBF was measured using a Xenon CT-CBF system. Fifteen minutes later after allowing them to smoke two pieces of cigarette, the second CBF measurement was performed. Subtraction CBF map was created to display the changes after smoking. CT images were taken at three levels so as to include the cerebral lobes, basal ganglia, limbic system, brainstem and cerebellum. Arterial nicotine increased up to the levels 8 times higher than before smoking. The increases of blood pressure and pulse rate were minimal. Arterial carbon dioxide level and hematocrit did not change. Feeling after smoking was variable in individual subject. In 8 subjects with a relatively high feeling, CBF increased mainly in the frontal lobe, hippocampus, uncus, thalamus and caudate nucleus. CBF did not change in the parietal, temporal and occipital lobes, and in the putamen, insula, brainstem and cerebellum. In two subjects with uncomfortable feeling, CBF did reduce in the whole brain. The CBF increase in frontal lobe and limbic structures seems to be secondary to nicotine-induced neuronal activation in each structure. Mesocorticolimbic dopamine system, which is believed to influence learning, memory or emotional performance, appears to be a target for nicotine. The CBF reduction in the whole brain might be due to cerebral vasoconstriction or be secondary to a systemic hypotension.

Adult↗
PubMed1995

Evidence for limbic system activation during CO2-stimulated breathing in man.

1. The role of supra-brainstem structures in the ventilatory response to inhaled CO2 is unknown. The present study uses positron emission tomography (PET), with infusion of H2(15)O, to measure changes in relative regional cerebral blood flow (rCBF) in order to identify sites of increased neuronal activation during CO2-stimulated breathing (CO2-SB) in awake man. 2. Five male volunteers were scanned during CO2-SB (mean +/- S.E.M.; end-tidal PCO2, 50.3 +/- 1.7 mmHg; respiratory frequency, 16.4 +/- 2.7 min-1; tidal volume, 1.8 +/- 0.2 l). As control, scans were performed during 'passive' isocapnic (elevated fraction of inspired CO2) positive pressure ventilation (end-tidal PCO2, 38.4 +/- 1.0 mmHg; respiratory frequency, 15.5 +/- 2.2 min-1; tidal volume, 1.6 +/- 0.2 l). With CO2-SB, all subjects reported dyspnoea. 3. The anatomical locations of the increases in relative rCBF (CO2-SB versus control) were obtained using magnetic resonance imaging. 4. Group analysis identified neuronal activation within the upper brainstem, midbrain and hypothalamus, thalamus, hippocampus and parahippocampus, fusiform gyrus, cingulate area, insula, frontal cortex, temporo-occipital cortex and parietal cortex. No neuronal activation was seen within the primary motor cortex (at sites previously shown to be associated with volitional breathing). 5. These results suggest neuronal activation within the limbic system; this activation may be important in the sensory and/or motor respiratory responses to hypercapnia in awake man.

Adult↗
PubMed2003

Early-onset anorexia nervosa: is there evidence of limbic system imbalance?

OBJECTIVE: This study, part of a continuing effort to understand the pathophysiology of the brain in early-onset anorexia nervosa, attempts to validate findings from an earlier study of regional cerebral blood flow and to correlate any abnormalities in blood flow with eating disorder psychopathology. METHOD: Fifteen newly referred children and adolescents with a diagnosis of anorexia nervosa (AN) underwent regional cerebral blood flow (rCBF) examination using single-photon computerized tomography (SPECT) and the Eating Disorders Examination (EDE) for children. RESULTS: Mean age was 14 years 11 months (SD = 1.35). Mean weight for height ratio was 82.79 % (SD = 10.66). SPECT findings showed that 11 (73%) had asymmetry (hypoperfusion) of blood flow in at least one area. Regions of the brain showing hypoperfusion included the temporal lobe (n = 9), parietal lobe (n = 5), frontal lobe (n = 3), thalamus (n = 3), and the caudate nuclei (n = 1). The median EDE subscale scores were high for all four subscales. Those patients with hypoperfusion had higher median EDE subscale scores than those without hypoperfusion, although the differences were not statistically significant. CONCLUSIONS: Most patients in our study had abnormal rCBF, predominantly affecting the temporal lobe, confirming our previous findings. There was no association with the EDE scores. The findings support earlier suggestions of an imbalance in neural pathways or circuits, possibly within the limbic system. This hypothesis is considered within the context of current knowledge and suggestions made with regard to how it might be tested.

Adolescent↗
PubMed1983

Distribution of neuropeptides in the limbic system of the rat: the bed nucleus of the stria terminalis, septum and preoptic area.

The distribution of the neuropeptides vasoactive intestinal polypeptide, cholecystokinin octapeptide, substance P, neurotensin, methionine-enkephalin and somatostatin has been mapped immunocytochemically in the bed nucleus of the stria terminalis, one of the major sites of termination for efferent projections from the amygdala. Immunoreactive fibres and terminals were distributed more or less topographically and largely in accordance with the previously described localization of peptide-containing cell bodies in the amygdala and the amygdaloid projection fields in the bed nucleus as described by neuroanatomical techniques. Thus, vasoactive intestinal polypeptide, which was found in some of the lateral amygdaloid nuclei, had a substantial projection to the lateral bed nucleus. The lateral bed nucleus also contained cholecystokinin-octapeptide, substance P, neurotensin and methionine-enkephalin immunoreactivity which probably derived from the central amygdaloid nucleus, whilst cholecystokinin-octapeptide, and especially substance P-containing fibres, were found in the medial bed nucleus and probably arise from cells in the medial amygdala. Reciprocal amygdalopetal projections were suggested by the presence of substance P- and somatostatin-containing cell bodies in the mediodorsal bed nucleus and vasoactive intestinal polypeptide cells in the lateral bed nucleus, but somatostatin otherwise had a widespread distribution. Numerous local peptidergic connections were also noted both within the bed nucleus and between it and adjacent structures, especially the preoptic area, hypothalamus and the basal ganglia. These data provide further evidence that neuropeptides play a major role in the connectivity of the limbic system and show that the bed nucleus of the stria terminalis is an important relay station, particularly between amygdaloid efferents and other forebrain areas.

Animals↗
PubMed2000

Acupuncture modulates the limbic system and subcortical gray structures of the human brain: evidence from fMRI studies in normal subjects.

Acupuncture, an ancient therapeutic technique, is emerging as an important modality of complementary medicine in the United States. The use and efficacy of acupuncture treatment are not yet widely accepted in Western scientific and medical communities. Demonstration of regionally specific, quantifiable acupuncture effects on relevant structures of the human brain would facilitate acceptance and integration of this therapeutic modality into the practice of modern medicine. Research with animal models of acupuncture indicates that many of the beneficial effects may be mediated at the subcortical level in the brain. We used functional magnetic resonance imaging (fMRI) to investigate the effects of acupuncture in normal subjects and to provide a foundation for future studies on mechanisms of acupuncture action in therapeutic interventions. Acupuncture needle manipulation was performed at Large Intestine 4 (LI 4, Hegu) on the hand in 13 subjects [Stux, 1997]. Needle manipulation on either hand produced prominent decreases of fMRI signals in the nucleus accumbens, amygdala, hippocampus, parahippocampus, hypothalamus, ventral tegmental area, anterior cingulate gyrus (BA 24), caudate, putamen, temporal pole, and insula in all 11 subjects who experienced acupuncture sensation. In marked contrast, signal increases were observed primarily in the somatosensory cortex. The two subjects who experienced pain instead of acupuncture sensation exhibited signal increases instead of decreases in the anterior cingulate gyrus (BA 24), caudate, putamen, anterior thalamus, and posterior insula. Superficial tactile stimulation to the same area elicited signal increases in the somatosensory cortex as expected, but no signal decreases in the deep structures. These preliminary results suggest that acupuncture needle manipulation modulates the activity of the limbic system and subcortical structures. We hypothesize that modulation of subcortical structures may be an important mechanism by which acupuncture exerts its complex multisystem effects.

Acupuncture Therapy↗
PubMed1993

A cyclic GMP-stimulated cyclic nucleotide phosphodiesterase gene is highly expressed in the limbic system of the rat brain.

Cyclic AMP and cyclic GMP serve as second messengers in a variety of neural cells, modulating their metabolic and electrical activity. The cyclic GMP-stimulated cyclic nucleotide phosphodiesterase, an enzyme whose hydrolytic activity is allosterically regulated by cyclic GMP in peripheral tissues, could play an important role in the regulation of cyclic nucleotide levels in the brain. To study the presence and distribution of cyclic GMP-stimulated phosphodiesterase in the rat brain, we cloned a portion of rat liver cyclic GMP-stimulated phosphodiesterase complementary DNA by polymerase chain reaction, using degenerate phosphodiesterase-specific oligonucleotide primers. Northern blot analysis of rat tissues reveals abundant expression of cyclic GMP-stimulated phosphodiesterase messenger RNA in the brain. Northern blot analysis of brain subregions shows especially strong expression in hippocampus and cortex, modest expression in the remainder of the forebrain and in the midbrain, and little expression in cerebellum and hindbrain. In situ hybridization studies with cyclic GMP-stimulated phosphodiesterase riboprobes confirm these northern blot results, and delineate cell groups with high levels of expression. Medial habenular nucleus is intensely labeled, as is hippocampus in the vicinity of pyramidal and granule cell bodies in areas CA1, CA2, CA3, and dentate gyrus. Other elements of the limbic system also contain cyclic GMP-stimulated phosphodiesterase messenger RNA, including olfactory and entorhinal cortices, subiculum, and amygdala. Additional cortical regions show more diffuse expression of cyclic GMP-stimulated phosphodiesterase messenger RNA, as do the basal ganglia. Cerebellum, thalamus, and hypothalamus do not show appreciable specific labeling. These studies demonstrate the presence of cyclic GMP-stimulated phosphodiesterase messenger RNA in specific regions of the rat brain, and suggest that the cyclic GMP-stimulated phosphodiesterase might modulate neuronal activity by regulating intracellular cyclic AMP levels in response to changes in intracellular cyclic GMP levels.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1999

Differential regulation of mRNAs for neuropeptide Y and its receptor subtypes in widespread areas of the rat limbic system during kindling epileptogenesis.

Expression of mRNAs for neuropeptide Y (NPY) and its receptor subtypes Y1 (Y1-R), Y2 (Y2-R) and Y5 (Y5-R) was studied in adult rat brain using in situ hybridization after 40 rapidly recurring seizures induced with 5-min interval by hippocampal kindling stimulations. At 2-4 h post-seizure, NPY mRNA levels were markedly elevated in dentate granule cells, CA1 and CA3 pyramidal layers, amygdala and piriform and entorhinal cortices. Gene expression had returned to control level in the dentate granule cell layer at 48 h but remained high in the other areas, reaching baseline at 1 week. Transient decreases of Y1-R mRNA levels were detected at 2-4 h in hippocampal subregions, amygdala, piriform, entorhinal and somatosensory cortices. The Y2-R mRNA levels were reduced at 2-4 h in the CA3 region and piriform cortex, but exhibited marked increases at 48 h and 1 week post-seizure in the dentate gyrus, amygdala and piriform and entorhinal cortices. At 3 weeks, Y2-R mRNA expression had virtually returned to baseline. Elevated Y5-R mRNA levels were only detected at 2-4 h and confined to dentate granule cell layer and piriform and entorhinal cortices. These results demonstrate a cell- and region-specific, differential regulation of mRNA expression for NPY and Y1-R, Y2-R, and Y5-R in the limbic system following recurring seizures. Because the gene changes were transient, it seems unlikely that the presumed alterations of the corresponding proteins are involved in the maintenance of the epileptic syndrome, which develops up to 4 weeks post-seizure in the present model and is stable thereafter. Our data provide further support for the hypothesis that the changes of NPY and its receptors act to dampen seizure susceptibility, and suggest that the cascade of gene changes is orchestrated to optimize this anticonvulsant effect.

Amygdala↗
PubMed1996

Synchronous GABA-mediated potentials and epileptiform discharges in the rat limbic system in vitro.

Application of 4-aminopyridine (4AP, 50 microM) to combined slices of adult rat hippocampus-entorhinal cortex-induced ictal and interictal epileptiform discharges, as well as slow field potentials that were abolished by the mu-opioid agonist [D-Ala2,N-Me-Phe4,Gly-ol5] enkephalin (DAGO, 10 microM) or the GABAA receptor antagonist bicuculline methiodide (BMI, 10 microM); hence, they represented synchronous GABA-mediated potentials. Ictal discharges originated in the entorhinal cortex and propagated to the hippocampus, whereas interictal activity of CA3 origin was usually recorded in the hippocampus. The GABA-mediated potentials had no fixed site of origin or modality of propagation; they closely preceded (0.2-5 sec) and thus appeared to initiate ictal discharges. Only ictal discharges were blocked by the antagonist of the NMDA receptor 3,3-(2-carboxypiperazine-4-yl)propyl-1-phosphonate (CPP, 10 microM), whereas the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) abolished all epileptiform activities. The GABA-mediated potentials continued to occur synchronously in all regions even after concomitant application of CNQX and CPP. [K+]o elevations were recorded in the entorhinal cortex during the ictal discharge (peak values = 13.9 +/- 0.9 mM) and the synchronous GABA-mediated potentials (peak values = 4.2 +/- 0.1 mM); the latter increases were presumably attributable to postsynaptic GABAa-receptor activation because they were abolished by DAGO or BMI. Their role in initiating ictal activity was demonstrated by using DAGO, which abolished both GABA-mediated synchronous potentials and ictal discharges. These data indicate that NMDA-mediated ictal discharges induced by 4AP originate in the entorhinal cortex; such a conclusion is in line with clinical evidence obtained in temporal lobe epilepsy patients. 4AP also induces GABA-mediated potentials that spread within the limbic system when excitatory transmission is blocked and may play a role in initiating ictal discharge by increasing [K+]o.

4-Aminopyridine↗