Tryptamine Concentrations in Areas of 5-Hydroxytryptamine Terminal Innervation After Electrolytic Lesions of Midbrain Raphe Nuclei

The possible existence of tryptamine-containing neurons originating in the midbrain raphe is suggested by several reports of tryptamine-mediated responses to electrical stimulation of the raphe nuclei. To assess this hypothesis, we have investigated the effects of electrolytic lesions of the median and dorsal raphe nuclei on striatal, hypothalamic, and hippocampal concentrations of tryptamine, 5-hydroxytryptamine (5-HT), and 5-hydroxyindoleacetic acid. In addition, the rat striatal tryptophan concentrations were also determined. No changes in the concentrations of tryptamine were observed at 1 or 2 weeks after lesioning the dorsal and median raphe nuclei, at which time the other 5-hydroxyindoles were markedly reduced; furthermore, no reductions were observed in tryptamine concentrations in the striatum, hypothalamus, or hippocampus of rats pretreated with a monoamine oxidase inhibitor. The only change observed in these rats was a limited increase in striatal tryptamine and tryptophan observed at 1 day after lesioning. The results indicate that tryptamine concentration is independent of the integrity of 5-HT-containing neurons of the midbrain raphe nuclei. Furthermore, if tryptamine-containing neurons that have terminal projections to the striatum, hypothalamus, and hippocampus exist, their cell bodies are located in regions outside the dorsal and median raphe nuclei. Another possibility could be that tryptamine is located in glial cells.     

Neural control of circadian rhythms in plasma ACTH, plasma corticosterone and motor activity

The circadian rhythms for plasma ACTH and corticosterone (B), as well as motor activity, were explored in female rats after ocular enucleation (O-X), stereotaxic lesion of the suprachiasmatic nuclei (SCN-X) or of midbrain raphe nuclei (R-X), or both O-X and R-X, pharmacological blockade of the serotoninergic (5HT) system by pCPA, sometimes bypassed by 5-HTP, or 5-HT denervation of the SCN by local injection of 5,7-DHT. The three circadian rhythms explored responded quite differently to the treatments. In particular, the ACTH and B rhythms lost their usual close correlations. The amplitude and mean level of ACTH fluctuations were depressed after all treatments, but remained normal or were enhanced for B rhythm. ACTH rhythmicity actually was undetectable after SCN-X, pCPA and, in several rats, combined O-X and R-X, whereas persisting circadian and/or ultradian B and locomotor activity rhythms were always measured. The participation of the suprachiasmatic nuclei, the midbrain raphe nuclei and other possible 5-HT components in a complex circadian pacemaker system is discussed.     

Influence of the medial raphe nucleus damage on discharge activity of the central and bazolateral nuclei of the amygdala

It has been revealed pronounced differences between neuronal discharge activity of central and basolateral nuclei of amygdala. After midbrain raphe medial nucleus damage discharge activity of amygdalar nuclei markedly changes, mainly by reciprocal manner. It is suggest that serotonergic afferentations from nucleus raphe to show various influence upon discharge activity of central and lateral nuclei of amygdala.     

Functional magnetic resonance imaging during hypotension in the developing animal.

Hypotension in adult animals recruits brain sites extending from cerebellar cortex to the midbrain and forebrain, suggesting a range of motor and endocrine reactions to maintain perfusion. We hypothesized that comparable neural actions during development rely more extensively on localized medullary processes. We used functional MRI to assess neural responses during sodium nitroprusside challenges in 14 isoflurane-anesthetized kittens, aged 14-25 days, and seven adult cats. Baseline arterial pressure increased with age in kittens, and basal heart rates were higher. The magnitude of depressor responses increased with age, while baroreceptor reflex sensitivity initially increased over those of adults. In contrast to a decline in adult cats, functional MRI signal intensity increased significantly in dorsal and ventrolateral medullary regions and the midline raphe in the kittens during the hypotensive challenges. In addition, significant signal intensity differences emerged in cerebellar cortex and deep nuclei, dorsolateral pons, midbrain tectum, hippocampus, thalamus, and insular cortex. The altered neural responses in medullary baroreceptor reflex sites may have resulted from disinhibitory or facilitatory influences from cerebellar and more rostral structures as a result of inadequately developed myelination or other neural processes. A comparable immaturity of blood pressure control mechanisms in humans would have significant clinical implications.     

Ontogenesis of serotoninergic nuclei in the rat stem

The development of central serotoninergic neurons has been investigated with immunohistochemical techniques using the indirect peroxidase-antiperoxidase (PAP) method in 16-and 19-day-old rat embryos, in 1, 10 and 26 days old young and in adult animals. Immunoreactive neurons were present on embryonic day 16 in the subventricular area of the brain stem. First the countour of nucleus raphe dorsalis became distinct in the subventricular cell mass of the lower midbrain. In the ventral part of the tegmentum, cells were grouped along the midline in bilateral columns from which the nucleus centralis superior, the nucleus raphe pontis and the nuclei pontis differentiated. These nuclei were well defined in the newborn on either side of the midline, and the nucleus centralis superior and nucleus raphe pontis were fused on the midline in 10-day old rat. In the ventral part of the pons and medulla, a bilateral cell mass was also found along the midline. A number of immunoreactive cells moving off the midline constituted the nucleus raphe magnus which was formed on 19. embryonis day. Another contingent of immunoreactive cells remained at the midline and formed the nuclei raphe obscurus and pallidus. In newborn rat, these nuclei were well separated from the nucleus raphe magnus. They would later fuse on the midline, whereas the nucleus raphe magnus would remain a bilateral structure.     

The serotonin-immunoreactive system of the suprachiasmatic nucleus in the hibernating ground squirrel,Spermophilus richardsonii

Summary In the suprachiasmatic nucleus (NSC) of hibernating and non-hibernating ground squirrels, the distribution of serotonin-immunoreactive (5HT-IR) fibers was studied by the use of the peroxidase-antiperoxidase technique. The cytology of perikarya giving rise to these suprachiasmatic 5HT-IR fibers was investigated in the anterior raphe nuclei. Differences in the immunoreactivity of suprachiasmatic fibers between hibernating and non-hibernating ground squirrels were determined by digital image analysis. The cellular activity was determined densitometrically after RNA-staining in anterior raphe neurons and suprachiasmatic perikarya. Abundant 5HT-IR fibers were observed in the medial and ventromedial portions of the NSC. Frequently, the fibers were found in close contact with perikarya of suprachiasmatic neurons. The central portion of the nucleus and the surrounding hypothalamic areas contained only a few scattered 5HT-IR fibers. Inside the raphe nuclei, 5HT-IR fibers and perikarya formed a dense network. In hibernating ground squirrels, the immunoreactivity to serotonin was approximately 45% higher than in non-hibernating controls. This difference is in accordance with signs of higher neuronal activity (40% higher RNA-content, 20% larger cell nuclei) in 5HT-IR perikarya of the raphe nucleus and the persisting activity of the NSC during hibernation; the activity of other brain regions dropped conspicuously in torpid animals.Supported by the Deutsche Forschungsgemeinschaft (Nu 36/2-1)     

Snca and Bdnf gene expression in the VTA and raphe nuclei of midbrain in chronically victorious and defeated male mice

Background

Alpha-synuclein (α-Syn) is a small neuronal protein that has been found to be expressed throughout the brain. It has been shown that α-Syn regulates the homeostasis of monoamine neurotransmitters and is involved in various degenerative and affective disorders. There is indication that α-Syn may regulate expression of the brain-derived neurotropic factor (BDNF) which plays an important role in the mood disorders.

Methodology/Principal Findings

The study aimed to analyze the mRNA levels of Snca and Bdnf genes in the ventral tegmental area (VTA) and raphe nuclei of the midbrain in male mice that had each won or defeated 20 encounters (20-time winners and 20-time losers, respectively) in daily agonistic interactions. Groups of animals that had the same winning and losing track record followed by a no-fight period for 14 days (no-fighting winners and no-fighting losers) were also studied. Snca mRNA levels were increased in the raphe nuclei in the 20-time losers and in the VTA of the 20-time winners. After no-fight period Snca mRNA levels decreased in both groups. Snca mRNA levels were similar to the control level in the VTA of the 20-time losers and in the raphe nuclei of the 20-time winners. However Snca gene expression increased in these areas in the no-fighting winners and no-fighting losers in comparison with respective mRNA levels in animals before no-fight period. Bdnf mRNA levels increased in VTA of 20-time winners. Significant positive correlations were found between the mRNA levels of Snca and Bdnf genes in the raphe nuclei.

Conclusions/Significance

Social experience affects Snca gene expression depending on brain areas and functional activity of monoaminergic systems in chronically victorious or defeated mice. These findings may be useful for understanding the mechanisms of forming different alpha-synucleinopathies.     

Lactate dehydrogenase isoenzyme spectrum in various areas of the reticular formation of the brain in rats: the effect of emotional stress

The changes in lactate dehydrogenase (LDG) isoenzyme content in the various brain areas were studied in intact Wistar rats and upon immobilization stress. LDG fraction levels were compared to BP changes during immobilization. The proportion of "anaerobic" LDG fractions was higher and the proportion of "aerobic" fractions lower in the dorsal area of midbrain substantia reticularis than in medulla oblongata reticular formation. The changes in LDG fraction content related to BP alterations during immobilization were observed in dorsal and ventral areas of midbrain (but not medulla oblongata) substantia reticularis. The proportion of anaerobic LDG4 fraction in the dorsal area of midbrain substantia reticularis was higher in rats with hypertensive responses, than in hypotensive animals. The changes in LDG5 fraction content were opposite. In the ventral area of midbrain reticular formation BP reduction was accompanied by a significant rise in "anaerobic" and a decrease in "aerobic" LDG fraction levels. The data obtained indicate certain differences in the intensity of aerobic and anaerobic processes of carbohydrate degeneration in various areas of substantia reticularis in control rats, as well as the correlation of changes in energy metabolism in the brain with BP alterations during emotional stress.     

Effects of thermal pain stimulus on EEG

Experiments were carried out on conscious rabbits with electrodes chronically implanted into sensorimotor cortex (MSC), ventro-postero-lateral thalamic nuclei (NVPL), periaqueductal grey matter (PAG) and midbrain reticular formation (MRF). Thermal pain stimulus (52 degrees C) lasted 10 s and was applied to the forepaw of the animal. Analysis of bioelectrical activity (20 sec periods) before and after the stimulation was performed by means of automatic methods using the algorithm of Fast Fourier Transform (FFT). It was found that pain stimulation resulted in a characteristic response in every studied structure and that this response was blocked by morphine.     

Extra-lemniscal afferent projections of dorsal spinal cord nuclei to the ventrobasal nuclear complex structure in the contralateral optic thalamus

It has been found that section of half the midbrain tegmentum in cats failed to prevent the afferent somatosensory projections from the foreleg to the ventrobasal nuclear complex of the contralateral thalamus. Specific evoked responses to the stimulation of the contralateral foreleg were recorded in this structure. These specific EP have the same latency as "lemniscal responses" (4-5 ms) and diminish the amplitude and duration of both components of the responses. Simultaneously, we have observed terminal axonal degeneration into the ventrobasal nuclear complex of the thalamus 5-7 days after the section of the contralateral midbrain tegmentum, using the electron microscopy method. All the results obtained indicate that the dorsal column nuclei have extra-lemniscal afferent connections with ventrolateral nuclear complex of the contralateral thalamus. These connections ascend in the back parts of the brainstem ipsilaterally to the corresponding pair of the dorsal column nuclei and rostrally to the midbrain on the contralateral side.     

Habenular modulation of raphe indoleamine metabolism

Anatomical and neurophysiological findings have demonstrated neuronal connections between the diencephalic habenular nuclei and brain stem serotonergic raphe nuclei. Therefore we examined some neurochemical consequences of habenular lesions. Sixteen hours and one week after bilateral lesions serotonin metabolism (as reflected by concentrations of its metabolite, 5-hydroxyindoleacetic acid) was significantly increased in the dorsal but not the median raphe nuclei. Unilateral lesions produced a proportionally smaller augmentation. Motron locomotor activity was enhanced during the light and dark illumination phases in lesioned animals but only attained statistical significance during the day.     

Changes in the Expression of Monoaminergic Genes under the Influence of Repeated Experience of Agonistic Interactions: From Behavior to Gene

The role of genetic and environmental factors as well as brain neurochemistry in regulating aggressive and submissive behaviors in animals are considered. We present a review of data on changes in brain monoaminergic activity (synthesis, catabolism, receptors) and on the expression of monoaminergic genes under repeated daily agonistic confrontations in male mice. A repeated experience of aggression was shown to result in the total activation of the dopaminergic systems and the inhibition of the serotonergic one. This was accompanied by a decrease in the mRNA level of the cathecol-O-methyltransferase gene in the midbrain and an increase of the mRNA level of the dopamine transporter and tyrosine hydroxylase genes in the ventral tegmental area of aggressive male mice. Repeated experience of social defeats produced dynamic changes in the serotonergic system of some brain areas and an increase of the mRNA level of the serotonin transporter and monoamine oxidase A genes in the midbrain raphe nuclei. Theoretical and methodological possibilities of the proposed ethological approach for studying molecular mechanisms of agonistic behavior are discussed in the context of the fundamental problem of investigating the ways of regulation from behavior to gene.     

The effect of dorsal raphe nucleus (DRN) lesions on the locomotor activity rhythm in mice.

The study employed electrical lesions of dorsal raphe nucleus (DRN) to determine the functional significance of those nuclei in the regulation of wheel-running activity rhythm in mice in light/dark (LD 12:12), constant light (LL), and constant dark (DD) conditions. The wheel-running records showed that raphe nucleus lesions resulted in few days' decrease in common activity and amplitude in LD. The activity phase was not compact but in fragmentary form, especially in DD condition. In some animals an earlier onset of activity after DRN lesion in LD was observed. In LL extension of the rhythm period occurred. Destruction of DRN only slightly modulates the wheel-running circadian rhythm in mice.     

大白鼠中缝核一氧化氮合酶阳性神经元的组织化学观察

中脑和脑桥部中缝核被认为与睡眠有直接和间接关系的重要脑结构。本文用一氧化氮合酶（ＮＯＳ）组织化学结合荧光组织化学方法证实在中缝核群中,ＮＯＳ阳性神经元主要定位于这两个脑部的中缝核内,ＮＯＳ产生的ＮＯ能使脑血管扩张,参与脑血流的调节。提示这二个脑部中缝核内的ＮＯＳ阳性神经元可能作为多种因素之一,参于睡眠状态下基本脑血流的维持     

Changes in the expression of monoaminergic genes under the influence of repeated experience of agonistic interactions: from behavior to gene

The role of genetic and environmental factors as well as brain neurochemistry in regulating aggressive and submissive behaviors in animals are considered. We present a review of data on changes in brain monoaminergic activity (synthesis, catabolism, receptors) and on the expression of monoaminergetic genes under repeated daily agonistic confrontations in male mice. A repeated experience of aggression was shown to result in the total activation of the dopaminergic system and the inhibition of the serotonergic one. This was accompanied by a decrease in the mRNA level of the catechol-O-methyltransferase gene in the midbrain and an increase of the mRNA level of the dopamine transporter and tyrosine hydroxylase genes in the ventral tegmental area of aggressive male mice. Repeated experience of social defeats produced dynamic changes in the serotonergic system of some brain areas and an increase of the mRNA level of the serotonin transporter and monoamine oxidase A genes in the midbrain raphe nuclei. Theoretical and methodological possibilities of the proposed ethological approach for studying molecular mechanisms of agonistic behavior are discussed in the context of the fundamental problem of investigating the ways of regulation from behavior to gene.     

Expression of apoptosis genes in the brain of rats with genetically defined fear-induced aggression

The programmed cell death (or apoptosis) plays an important role both in developing and mature brains. Multiple data indicate the involvement of processes of apoptosis in mechanisms of different psychopathologies. At the same time, nothing is known about the role of apoptosis in the regulation of genetically defined aggression. In the present work, the expression of the genes that encode main pro- and antiapoptotic BAX and BCL-XL proteins, as well as caspase 3 (the main effector of apoptosis), in different brain structures of rats that were selected on a high aggression towards human (or its absence) was studied. A significant increase in the expression of the gene encoding caspase 3 was detected in the hypothalamus. This was accompanied by a significant decrease in the expression of proapoptotic Bax gene in the hippocampus and increase in mRNA level of antiapoptotic Bcl-xl gene in the raphe nuclei area of midbrain in highly aggressive rats. An increase in the ratio Bcl-xl: Bax was found in the midbrain and amygdala; a trend towards an increase in the ratio was also found in hippocampus of aggressive animals compared to tame animals. Thus, we demonstrated that genetically defined fear-induced aggression is associated with significant changes in the genetic control of apoptosis in the brain. It is assumed that an increase in the Bcl-xl gene expression (accompanied by a decrease in the Bax gene expression) can indicate an increase in the threshold of neuronal apoptosis in highly aggressive rats.     

Quantitative and qualitative automatic evaluation of afterdischarges in the study of antiepileptic drugs

An automatic analysis of bioelectrical activity in some structures of the rabbit's brain was performed after i.v. administration of diazepam, phenytoin or phenobarbital. It was found that diazepam raised the ratio of fast activity in the afterdischarges pattern but paralelly decreased the total energy involved in the production of after-discharges in the cortex and midbrain reticular formation. Phenobarbital caused a significant shift in frequencies, increasing the ratio of slow activities (in the exception of hippocampus) and decreased the power spectra of afterdischarges in all structures (in the exception of midbrain reticular formation). Phenytoin, similarly to phenobarbital, decreased the ratio of fast activities. This effect was significant only in thalamus and midbrain reticular formation. At the same time it increased the total power of signal from hippocampus and midbrain reticular formation.     

Downregulation of Serotonergic Gene Expression in the Raphe Nuclei of the Midbrain Under Chronic Social Defeat Stress in Male Mice

There is ample experimental evidence supporting the hypothesis that the brain serotonergic system is involved in the control of chronic social defeat stress (CSDS), depression, and anxiety. The study aimed to analyze mRNA levels of the serotonergic genes in the raphe nuclei of midbrain that may be associated with chronic social defeats consistently shown by male mice in special experimental settings. The serotonergic genes were the Tph2, Sert, Maoa, and Htr1a. The Bdnf and Creb genes were also studied. The experimental groups were composed of male mice with experience of defeats in 21 daily encounters and male mice with the same track record of defeats followed by a no-defeat period without agonistic interactions (relative rest for 14 days). It has been shown that mRNA levels of the Tph2, Maoa, Sert, Htr1a, Bdnf, and Creb genes in the raphe nuclei of defeated mice are decreased as compared with the controls. The expression of the serotonergic genes as well as the Creb gene is not restored to the control level after the 2 weeks of relative rest. mRNA levels of Bdnf gene are not recovered to the control levels, although some upregulation was observed in rested losers. CSDS experience inducing the development of mixed anxiety/depression-like state in male mice downregulates the expression of serotonergic genes associated with the synthesis, inactivation, and reception of serotonin. The Bdnf and Creb genes in the midbrain raphe nuclei are also downregulated under CSDS. Period of relative rest is not enough for most serotonergic genes to recover expression to the control levels.