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PubMed1978

Neuronal plasticity in the limbic system during classical conditioning of the rabbit nictitating membrane response. II: Septum and mammillary bodies.

Neuronal unit activity was recorded from several limbic system structures during classical conditioning of the rabbit nictiating membrane response to a tone CS. Air puff to cornea was used as a UCS. The present and past investigations of hippocampal activity using this paradigm show a neuronal plasticity which develops early in training, increases rapidly and shifts forward in time as behavioral conditioning develops. Recordings from the lateral septal region demonstrate the same within-trial pattern of unit discharge seen in hippocampus, indicating a projection of hippocampal plasticity over precommissural fornix pathways. Medial septal neurons, on the other hand, respond in an excitatory manner to the onsets of tone and air puff stimulation. While unit discharges seen in hippocampus and lateral septum occur only during the paired (learning) paradigm, medial septal activity is identical under both paired and unpaired (control) conditions. The latter fact lends support for a sensory interpretation of medial septal responses, and is consistent with anatomical evidence of a major septohippocampal projection originating from this region. In contrast to results for lateral septum, recordings from medial and lateral mammillary nuclei indicate only small, diffuse excitation that exhibits no consistent changes over training, and is not related to activity seen in hippocampal or septal regions. The apparent lack of correspondence between learning dependent unit measures obtained from pre- and postcommissural fornix structures is entirely consistent with current modified descriptions of limbic system anatomy.

Action Potentials↗
PubMed2006

Corticotropin-releasing factor in the dorsal raphe elicits temporally distinct serotonergic responses in the limbic system in relation to fear behavior.

The neurotransmitters serotonin and corticotrophin-releasing factor are thought to play an important role in fear and anxiety behaviors. This study aimed to determine the relationship between corticotrophin-releasing factor-evoked changes in serotonin levels within discrete regions of the limbic system and the expression of fear behavior in rats. The effects of corticotrophin-releasing factor administration to the serotonin cell body regions of the dorsal raphe nucleus on fear behavior, behavioral activity, and extracellular serotonin levels were assessed in freely moving rats with microdialysis probes implanted into the central nucleus of the amygdala and the medial prefrontal cortex. Infusion of corticotrophin-releasing factor (0.5 microg) into the dorsal raphe rapidly induced freezing behavior, which was positively correlated with an immediate increase in serotonin release in the central nucleus of the amygdala. In contrast, cessation of freezing behavior correlated with a delayed and prolonged increase in serotonin release within the medial prefrontal cortex. Our findings suggest that corticotrophin-releasing factor-induced freezing behavior is associated with regionally and temporally distinct serotonergic responses in the limbic system that may reflect differing roles for these regions in the expression of fear/anxiety behavior.

Analysis of Variance↗
PubMed1977

Carbamazepine in the dyscontrol syndrome associated with limbic system dysfunction.

The literature has long demonstrated an association between certain behavioral problems and EEG abnormalities, particularly the association of aggressive and sometimes violent behavior with foci in the temporal lobes. The concept of "dyscontrol syndromes" has also been established and it is possible that some instances of the dyscontrol syndrome arise from an abnormal sensitization of the limbic system, due to disturbance in or near the temporal lobes. Carbamazepine is an interesting new drug, with both anticonvulsant and psychotropic properties, for which both the behavioral effects and pharmacological actions have been defined. The properties of carbamazepine for blocking polysynaptic reflexes and suppressing post-tetanic potentiation are discussed with respect to this limbic system dysfunction in the dyscontrol syndrome. It is also proposed that this drug might be considered for its psychotropic effect in certain instances of dyscontrol, with or without clinical diagnosis of epilepsy. An illustrative case is cited.

Adult↗
PubMed1976

Differential effect of neuroleptic drugs on dopamine turnover in the extrapyramidal and limbic system.

In gallamine-immobilized cats, the caudate nucleus and the nucleus accumbens septi were perfused by means of a push-pull cannula and dopamine was measured in the perfusate. Chlorpromazine (10 mg kg(-1)) and clozapine (20 mg kg(-1)), administered intravenously, enhanced the release of dopamine. The effect of chlorpromazine was similar in both regions whereas that of clozapine was more pronounced in the nucleus accumbens than in the caudate nucleus. Furthermore, in the rat, sulpiride, clozapine and thioridazine increased the homovanillic acid concentration in striatum and limbic system to a similar extent. However, following probenecid administration, the net effect of these drugs on homovanillic acid accumulation was more marked in the limbic system than in the striatum whereas haolperidol and chlorpromazine had a similar effect in the two regions. It is concluded that, in contrast to haloperidol and chlorpromazine, sulpiride, clozapine and thioridazine may preferentially affect the limbic dopaminergic transmission. This possibly accounts for the fact that sulpiride, clozapine and thioridazine display an antipsychotic action and yet cause less extrapyramidal side effects than haloperidol and chlorpromazine.

Animals↗
PubMed1986

[Various neurochemical aspects of the action of the tetrapeptide tuftsin on limbic system structures (histochemical and biochemical study)].

Tetrapeptide tuftsin action on the activity of succinate dehydrogenase (SDG), malate dehydrogenase (MDG) and monoamine-oxidase (MAO) in microstructures of the neocortex, hippocampus and hypothalamus (supraoptic and paraventricular nuclei, retrochiasmic zone) has been investigated by means of histochemical methods. Simultaneously, pyruvate-, malate-, glutamate-, alfaketoglutamate-, succinate- and lactate-dehydrogenase activity in the neocortex and in the structures of the limbic system has been studied biochemically. SDG and MDG activity increases in neurons and glycocytes of all the hypothalamic formations mentioned. Changes in the activity of dehydrogenases in the hippocampus and neocortex under the same stimulation are less pronounced. MAO activity also increases in the nerve terminals converging on the bodies and dendrites of hypothalamic neurons and in the preterminal fibers of the neocortex, Tuftsin increases oxidative-reducing processes in various structures of the brain, but at the same time it possesses a predominant influence on the limbic system structures.

Animals↗
PubMed1975

A case of limbic system dysfunction with hypersexualith and fugue state.

This paper describes a case of limbic dysfunction in a 28-year-old female veteran who presented with psychoses and sexual promiscuity. She had EEG abnormalities and showed dramaic improvement with anti-convulsant medication. Limbic system dysfunction in general may present as "functional psychoses." The literature is briefly reviewed.

Adult↗
PubMed1997

Parkinson's disease and depression: evidence for an alteration of the basal limbic system detected by transcranial sonography.

OBJECTIVES: Depression is a frequent symptom in Parkinson's disease. Compelling evidence suggests a role of the brainstem in the control of mood and cognition. In patients with unipolar depression transcranial sonography (TS) studies have shown structural alteration of the mesencephalic brainstem raphe which could suggest an involvement of the basal limbic system in the pathogenesis of primary mood disorders. The objective of the present study was to evaluate whether a similar alteration could be found in depressed patients with Parkinson's disease using TS. METHODS: Thirty patients with Parkinson's disease and 30 age and sex adjusted controls were examined by TS. Raphe echogenicity was rated semiquantitatively. The severity of motor symptoms and depression was rated using standard research instruments. RESULTS: Raphe echogenicity was significantly reduced in depressed patients with Parkinson's disease compared with nondepressed patients with Parkinson's disease and control subjects. Raphe echogenicity correlated negatively with degree of motor impairment, and differences in raphe echo between depressed and non-depressed patients with Parkinson's disease were upheld when motor impairment was controlled for. CONCLUSION: These preliminary findings suggest that, as in unipolar depression, a morphological alteration of the brainstem raphe might be involved in the pathogenesis of depression in Parkinson's disease. This raphe alteration may reflect involvement in the basal limbic system in the pathogenesis of secondary depression. This concept is in line with current knowledge on the pathogenesis of both depression in Parkinson's disease and primary depressive disorders.

Aged↗
PubMed2005

The integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 as evidenced by fMRI.

Clinical and experimental data indicate that most acupuncture clinical results are mediated by the central nervous system, but the specific effects of acupuncture on the human brain remain unclear. Even less is known about its effects on the cerebellum. This fMRI study demonstrated that manual acupuncture at ST 36 (Stomach 36, Zusanli), a main acupoint on the leg, modulated neural activity at multiple levels of the cerebro-cerebellar and limbic systems. The pattern of hemodynamic response depended on the psychophysical response to needle manipulation. Acupuncture stimulation typically elicited a composite of sensations termed deqi that is related to clinical efficacy according to traditional Chinese medicine. The limbic and paralimbic structures of cortical and subcortical regions in the telencephalon, diencephalon, brainstem and cerebellum demonstrated a concerted attenuation of signal intensity when the subjects experienced deqi. When deqi was mixed with sharp pain, the hemodynamic response was mixed, showing a predominance of signal increases instead. Tactile stimulation as control also elicited a predominance of signal increase in a subset of these regions. The study provides preliminary evidence for an integrated response of the human cerebro-cerebellar and limbic systems to acupuncture stimulation at ST 36 that correlates with the psychophysical response.

Acupuncture↗
PubMed2002

Identification and localization of multiple classic cadherins in developing rat limbic system.

Classic cadherins are multifunctional adhesion proteins that play roles in tissue histogenesis, neural differentiation, neurite outgrowth and synapse formation. Several lines of evidence suggest that classic cadherins may establish regional or laminar recognition cues by virtue of their differential expression and tight, and principally homophilic, cell adhesion. As a first step toward investigating the role this family plays in generating limbic system connectivity, we used RT-PCR to amplify type I and type II classic cadherins present in rat hippocampus during the principal period of synaptogenesis. We identified nine different cadherins, one of which, cadherin-9, is novel in hippocampus. Using in situ hybridization, we compared the cellular and regional distribution of five of the cadherins (N, 6, 8, 9 and 10) during the first two postnatal weeks in hippocampus, subiculum, entorhinal cortex, cingulate cortex, anterior thalamus, hypothalamus and amygdala. We find that each cadherin is differentially distributed in distinct, but highly overlapping fields that largely correspond to known anatomical boundaries and are often coordinately expressed in interconnected regions. For example, cadherin-6 expression defines CA1 and its principal target, the subiculum; cadherin-10 is differentially expressed in CA1 and CA3 in a manner correlating with the organization of interconnecting Schaffer collateral axons; and cadherin-9 shows a striking concentration in CA3. Some cadherin mRNAs are highly restricted to particular anatomical fields over the entire time course, while others are more broadly expressed and become concentrated within particular domains coincident with the timing of afferent ingrowth. Our data indicate that classic cadherins are sufficiently diverse and differentially distributed to support a role in cell surface recognition and adhesion during the formation of limbic system connectivity.

Amygdala↗
PubMed2002

Network and pharmacological mechanisms leading to epileptiform synchronization in the limbic system in vitro.

Seizures in patients presenting with mesial temporal lobe epilepsy result from the interaction among neuronal networks in limbic structures such as the hippocampus, amygdala and entorhinal cortex. Mesial temporal lobe epilepsy, one of the most common forms of partial epilepsy in adulthood, is generally accompanied by a pattern of brain damage known as mesial temporal sclerosis. Limbic seizures can be mimicked in vitro using preparations of combined hippocampus-entorhinal cortex slices perfused with artificial cerebrospinal fluid containing convulsants or nominally zero Mg(2+), in order to produce epileptiform synchronization. Here, we summarize experimental evidence obtained in such slices from rodents. These data indicate that in control animals: (i) prolonged, NMDA receptor-dependent epileptiform discharges, resembling electrographic limbic seizures, originate in the entorhinal cortex from where they propagate to the hippocampus via the perforant path-dentate gyrus route; (ii) the initiation and maintenance of these ictal discharges is paradoxically contributed by GABA (mainly type A) receptor-mediated mechanisms; and (iii) CA3 outputs, which relay a continuous pattern of interictal discharge at approximately 1Hz, control rather than sustain ictal discharge generation in entorhinal cortex. Recent work indicates that such a control is weakened in the pilocarpine model of epilepsy (presumably as a result of CA3 cell damage). In addition, in these experiments electrographic seizure activity spreads directly to the CA1-subiculum regions through the temporoammonic pathway. Studies reviewed here indicate that these changes in network interactions, along with other mechanisms of synaptic plasticity (e.g. axonal sprouting, decreased activation of interneurons, upregulation of bursting neurons) can confer to the epileptic, damaged limbic system, the ability to produce recurrent limbic seizures as seen in patients with mesial temporal lobe epilepsy.

4-Aminopyridine↗
PubMed1998

Distribution of GABAA receptors in the limbic system of alcohol-preferring and non-preferring rats: in situ hybridisation histochemistry and receptor autoradiography.

The present study has employed quantitative receptor autoradiography and in situ hybridisation histochemistry to compare the expression of the mRNA encoding the alpha 1 and alpha 2 subunits of the GABAA receptor and the binding density of mature GABAA receptors in the limbic system of alcohol-preferring Fawn-Hooded rats (FH) with Wistar-Kyoto rats (WKY). Quantifiable levels of mRNA encoding the alpha 1 subunit were found in cortical regions, ventral pallidum, substantia nigra, horizontal limb of the diagonal band and the hippocampus of both rat strains. Interestingly, expression of the alpha 1 subunit mRNA was decreased by approximately 30% in the hippocampus of FH compared to WKY rats. Following a 28-day period with free access to 10% ethanol, expression of the alpha 1 subunit transcript, was significantly increased in the piriform cortex and horizontal limb of the diagonal band, unaltered in the hippocampus but decreased in the substantia nigra of FH rats. Quantifiable levels of mRNA encoding the alpha 2 subunit were found in nucleus accumbens, amygdala, cortical regions, lateral septal nucleus, hippocampus, medial habenula and ventral pallidum of both strains. Expression of the alpha 2 subunit mRNA was decreased by approximately 35% in both the hippocampus and occipital cortex of FH compared to WKY rats. However, consumption of 10% ethanol in FH rats had no impact upon expression of the mRNA encoding the alpha 2 subunit in any region examined. Mature GABAA receptors were studied by autoradiography utilising the antagonist radioligand [3H]SR95531 and the agonist radioligand [3H]muscimol. Topographic binding throughout the limbic system of both strains was observed for both radioligands. Specifically, [3H]SR95531 binding was higher in the occipital cortex, hippocampus, lateral septal nucleus, superior colliculus and ventral pallidum of the FH rats compared to WKY rats; however, in the nucleus accumbens [3H]SR95531 binding was lower in FH compared to WKY. Ethanol consumption had no measurable effect on the binding of [3H]SR95531 in FH rats. In the case of [3H]muscimol, binding was higher in the cortex, lateral septum and ventral pallidum of FH compared to WKY. Furthermore, ethanol consumption resulted in a 25-30% increase in [3H]muscimol binding in the lateral septum and striatum of FH rats. These data provide evidence for differential expression of GABAA receptor subunits in FH and WKY rats, and additionally indicate anatomically defined variations in GABAA receptor binding between the two rat strains.

Alcohol Drinking↗
PubMed1981

Enhancement of osmotic thirst elicited by electric stimulation of the limbic system in dogs.

Seven dogs were chronically implanted with 30 electrodes directed at various structures of the basal forebrain. Osmotic thirst threshold (expressed as an increase in plasma osmolality and a decrease in cellular water content caused by an intravenous infusion of 5% NaCl, necessary to induce drinking) was measured during electric stimulation of the basal forebrain and compared to that found under control conditions. Stimulation through 11 electrodes located in the lateral part of the septum (5 locations) and other parts of the limbic system markedly decreased the osmotic thirst threshold. The increment in plasma osmolality necessary to elicit drinking decreased from 9.7 +/- 1.3 to 4.8 +/- 1.2 mmol/kg (n = 11). The volume of water drunk at the thirst threshold did not differ significantly. A significant augmentation of the volume of water drunk during 1 h following infusion of hypertonic saline was observed when the infusion was combined with stimulation of the gyrus rectus, precommissural septum and nucleus accumbens. These and previous results (SZCZEPANSKA-SADOWSKA et al., 1979) suggest that the limbic system of the basal forebrain exerts both excitatory and inhibitory influences on the thirst system. The prolonged poststimulatory overdrinking indicates that enhancement of osmotic thirst cannot be entirely explained by an immediate action of the stimulating current on the neurons of the thirst system.

Animals↗
PubMed1978

[Relationship between the limbic system and gonadal function. 3. Quantifiable prepuberal morphokinesis of the basolateral amygdaloid body and the ventral hippocampus formation].

In juvenile female rats the neurons of the limbic system which are attached to the basolateral amygdaloid nucleus and to a circumscribed area of ventral hippocampal formation are characterised by markedly quantifiable morphokinesis between the 21st day of age and onset of the first oestrus. This morphokinesis will take the form of consecutively occurring highly significant volume alterations of the cell nuclei which, in turn, reflect variation in neuronal activity. Some of such variation represents a expression of the general maturation and differentiation of central nervous neurons. The time of occurrence of such variation as well as its peculiar nature also appear to suggest the existence of some special relationship to sexual maturation. This seems to support the conclusion that the basolateral amygdaloid nucleus and the ventral hippocampal formation are attached to the extrahypothalamic central nervous structures of the cerebro-hypophyseal-gonadal axis, in addition to the medial and cortical amygdaloid nuclei. However, the very nature of relationships that may exist between the two investigated components of the limbic system, on the one hand, and sexual maturation as well as gonadal function, on the other, cannot be derived from the results reported in this paper.

Amygdala↗
PubMed1993

Quantitative autoradiography of somatostatin receptors in the rat limbic system.

The distribution of somatostatin receptors (SRIF-R) was analyzed in the limbic system of the adult rat by in vitro autoradiography with [125I-Tyr0,DTrp 8]S14 as a radioligand. Precise quantification of the density of binding sites, at 0.2 mm intervals throughout the different areas revealed a marked heterogeneity of labeling in most structures. In particular, SRIF-R were concentrated in the basal (104.4 +/- 3.3 fmol/mg proteins) and basolateral amygdaloid nuclei (94.8 +/- 4.3 fmol/mg proteins), and in the nucleus of the lateral olfactory tract (121.6 +/- 2.4 fmol/mg proteins), whereas moderate densities were detected in the amygdalo-hippocampal nucleus (76.4 +/- 2.8 fmol/mg proteins). The medial (41.3 +/- 1.9 fmol/mg proteins) and the central (24.0 +/- 1.4 fmol/mg proteins) amygdaloid nuclei contained lower SRIF-R concentrations. It appears from these observations, in the light of the anatomical pathways of the amygdala, that intra-amygdalian SRIF-containing neurons project to the amygdalo-hippocampal nucleus, and that SRIF-R in the basolateral complex are the target of afferents from limbic cortical areas. SRIF-R were detected at different levels of the hippocampal formation but their distribution was more restricted than that of SRIF-containing fibers. The maximal density of sites was detected in the ventral and dorsal parts of the subiculum (115.0 +/- 3.4 and 87.0 +/- 2.8 fmol/mg proteins, respectively) and in the parasubiculum (100.1 +/- 5.4 fmol/mg proteins). In Ammon's horn, the stratum oriens and stratum radiatum of the CA1 field were the only sites enriched in SRIF-R (74.1 +/- 2.0 and 74.6 +/- 1.9 fmol/mg proteins, respectively). The apparent lack of receptors in the pyramidal cell layer indicated that, in Ammon's horn, SRIF is involved in intra-hippocampal communication. Low levels of receptors were found in the hippocampal CA2 and CA3 fields. SRIF-R in the dentate gyrus were mainly concentrated in the molecular layer (57.3 +/- 1.2 fmol/mg proteins). A very high density of sites was also observed in the entorhinal cortex (up to 123.1 +/- 1.5 fmol/mg proteins). A clear mismatch between SRIF and SRIF-R was detected in the septum and the habenula. In the profound layers of the cingulum and retrosplenial cortex, a heterogeneous distribution of SRIF-R was observed. High concentrations of sites were detected in the rostral zone of the cingulate cortex (93.4 +/- 2.0 fmol/mg proteins) while the posterior cingulate only exhibited moderate concentrations of sites (66.5 +/- 0.7 fmol/mg proteins).(ABSTRACT TRUNCATED AT 400 WORDS)

Amygdala↗
PubMed1980

Stereotactic lesions in primary epilepsy of the limbic system.

Chronic depth electrodes have proven useful in diagnosing primary epilepsy of the limbic system. Five patients had small lesions in the amygdala and hippocampus. There was a 50% reduction of the seizures frequency. No complication were observed and patients were ambulant the day following surgery. It is felt that stereotactic lesions larger than produced by the leucotome used should be performed provided we have proofs that the epileptogenic focus is in a restricted area. Stereotactic lesions may also have a role in interrupting pathways clearly proven as participating in the epileptic discharge. Only under these conditions, will it be possible to say that stereotactic lesions are effective in specific type of epilepsy.

Amygdala↗
PubMed1989

Oestrogen receptors and effects of oestradiol administration on mRNA synthesis in the limbic system of the neonatal female rat.

There is sexual dimorphism of specific species of mRNA in the neonatal rat brain and this sexual dimorphism may be imprinted by steroids of testicular origin during the perinatal period. According to current theories, only aromatizable androgens may cause sexual differentiation of sexual behaviour and function in the adult. The effects of oestradiol benzoate on mRNA synthesis in the neonatal female limbic system were therefore studied. In addition, cytosolic and nuclear oestrogen receptors were measured after administration of testosterone propionate, oestradiol benzoate or dihydrotestosterone (DHT). An attempt was made to distinguish between the brain oestrogen receptor and the plasma oestrogen-binding protein, alphafoetoprotein (AFP) by isoelectric focussing. After injection of 50 micrograms oestradiol benzoate s.c. to neonatal female rats, the expression of mRNA coding for sexually dimorphic proteins appeared to be changed to a male-type pattern. The overall density of labelling was noticeably greater and specific changes in labelled proteins were observed. These effects were observed within 3 h of injection. Both testosterone and oestradiol caused a marked depletion of cytosolic oestrogen receptors in the limbic system whereas DHT was ineffective in this respect. Nuclear receptors were present in equal abundance in male- and female-derived nuclei and only oestradiol was able to cause a significant (P less than 0.025) increase in nuclear oestrogen receptors. The receptor and AFP could be distinguished by isoelectric focussing, since the pI of the receptor was 7.05, while that of AFP was 4.5. These results are consistent with the possibility that oestradiol alters transcription in the neonatal rat brain and may do this through the oestrogen receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Relation between age-related changes in hyper-emotionality and serotonergic neuronal activities in the rat limbic system.

To examine the relationship between higher concentrations of 5-HT and 5-HIAA in the aged rat brain and their hyper-emotionality, behavioral and neurochemical studies were performed. In the behavioral studies, under novel circumstances, the aged rats showed an significant increase in defecation. Furthermore, their locomotor activity was much less than that of young rats, and the numbers of head-dips of aged rats were significantly decreased compared to those of young rats. In the neurochemical studies, the concentrations of 5-HT and 5-HIAA in the limbic system (e.g., hippocampus, amygdala and septal area) of aged rats were much higher than those of young rats (P < 0.001) under normal conditions. The possibility that the hyper-emotionality of aged rats might be related to the hyper-activities of serotonergic neurons in their limbic system were taken into consideration when the results were analyzed.

Aging↗
PubMed1983

Synthesis rate of dopamine: difference between corpus striatum and limbic system as a possible explanation of variations in reactions to drugs.

The synthesis rate of dopamine and noradrenaline in different parts of the rat brain was estimated by measuring the accumulation of DOPA following decarboxylase inhibition. Although the synthesis of dopamine was enhanced in all regions by haloperidol and gammabutyrolactone, it was increased to almost 400% of the control in the corpus striatum but to only somewhat more than 200% in the olfactory tubercle and some other limbic regions. The dopamine autoreceptor agonist B-HT 920 was more potent and effective in lowering the synthesis of dopamine in the limbic regions than in the corpus striatum. These differences between the extrastriatal and striatal brain areas in the pharmacological responses might be explained by a 50% higher norma synthesis rate constant of the dopamine in the limbic system than in the corpus striatum. The lower dopamine synthesis rate in the latter region may be due to a negative neuronal feedback from the corpus striatum to the substantia nigra. Functional studies support this proposal. Indeed, B-HT 920 was less effective than haloperidol in changing the direction of head turning of rats with a diencephalic hemisection at doses equieffective in reducing the motor activity. The findings indicate that B-HT 920 is relatively more potent than haloperidol in inhibiting the dopamine neurotransmission in the limbic system than in the corpus striatum.

Animals↗