Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria terminalis project to the midbrain central gray in the rat.

The central nucleus of the amygdala, bed nucleus of the stria terminalis, and central gray are important components of the neural circuitry responsible for autonomic and behavioral responses to threatening or stressful stimuli. Neurons of the amygdala and bed nucleus of the stria terminalis that project to the midbrain central gray were tested for the presence of peptide immunoreactivity. To accomplish this aim, a combined immunohistochemical and retrograde tracing technique was used. Maximal retrograde labeling was observed in the amygdala and bed nucleus of the stria terminalis after injections of retrograde tracer into the caudal ventrolateral midbrain central gray. The majority of the retrogradely labeled neurons in the amygdala were located in the medial central nucleus, although many neurons were also observed in the lateral subdivision of the central nucleus. Most of the retrogradely labeled neurons in the BST were located in the ventral and posterior lateral subdivisions, although cells were also observed in most other subdivisions. Retrogradely labeled neurotensin, corticotropin releasing factor (CRF), and somatostatin neurons were mainly observed in the lateral central nucleus and the dorsal lateral BST. Retrogradely labeled substance P-immunoreactive cells were found in the medial central nucleus and the posterior and ventral lateral BST. Enkephalin-immunoreactive retrogradely labeled cells were not observed in the amygdala or bed nucleus of the stria terminalis. A few cells in the hypothalamus (paraventricular and lateral hypothalamic nuclei) that project to the central gray also contained CRF and neurotensin immunoreactivity. The results suggest the amygdala and the bed nucleus of the stria terminalis are a major forebrain source of CRF, neurotensin, somatostatin, and substance P terminals in the midbrain central gray.     

中华蟾蜍中脑组织学研究

采用HE染色和Holmes银染法对蟾蜍中脑的显微结构进行了研究.中脑背侧,视叶可分为顶盖和被盖,顶盖从外侧到内侧依次分为:带状层、外灰质层、浅白质层、中灰质层、中白质层、深灰质层、深白质层和中央灰质.被盖前端分层与顶盖相同,后端分层不明显.中脑腹侧包括被盖和大脑脚,HE染色和Holmes银染法显示,大脑脚从外向内颜色由浅变深,存在大量纵向神经纤维束,两脚底分界处有横向交错的神经纤维.被盖外侧细胞不分层,聚集形成核团.被盖内侧,细胞和纤维以中脑水管为中心,呈同心圆环分8层.通过比较蟾蜍中脑背腹差异程度,了解背腹功能不同.同时对中华蟾蜍中脑同其他脊椎动物的进行了比较.     

Formation of a conditioned "passive" avoidance reaction following ablation of the midbrain central gray]

Formation of conditioned "passive" avoidance reaction was studied in rats with a single pain reinforcement after electrolythic destruction of mesencephalic part of the central gray substance (CGS). The ablation of CGS ventral nuclei at the level of the midbrain rostral part led to a decrease in emotional reaction of "fears" and to disturbance of avoidance conditioning. The participation of midbrain limbic structures in learning and memory is discussed.     

Effect of electroacupuncture on the activity of neurons in the central gray matter of the midbrain

The effect of electroacupuncture in locally-segment and general analgetic points on background impulse activity of central gray substance neurons and their activity caused by nociceptive stimulation of the dental pulp, infraorbital nerve and forearm skin surface was studied in acute experiments on cats. It has been established that general analgetic points are better represented in the central gray substance, as compared to locally-segment points. Different degree involvement of central gray substance in the realization of acupuncture analgetic effect in different points is postulated. The role of dorsal and ventral compartments of the central gray substance in acupunctural analgesia is discussed.     

Substance P in the central mechanism of the rabbit feeding response evoked by stimulation of the lateral hypothalamus

The effects of substance P on the central mechanisms of food motivation elicited by electrical stimulation of the lateral hypothalamus were studied in chronic experiments on rabbits. Intravenous injection of substance P (30 micrograms/kg) brought about a dramatic reduction in the excitability of the "food center" in the hypothalamus, which returned to normal 45-60 minutes after injection. Higher concentrations of substance P provoked food behavior inversion up to the replacement of food motivation by avoidance behavior. Intravenous injections of substance P disturbed the relationships between the hippocamp, midbrain reticular formation and hypothalamus seen in health. This manifested in complete cessation of the inhibitory effects of the dorsal hippocamp and facilitating influences of the midbrain reticular formation on the excitability of the hypothalamic "food center". It is assumed that disorders of the central mechanisms of food motivation may arise from the effects produced by substance P directly on the central nervous system or on the brain via changes in the hormonal balance and responses of the autonomous nervous system.     

Role of serotonin receptors in the amygdaloid complex and central gray substance in conditioned passive avoidance reaction in rats

The functional role of 5-HT1 receptors in the memory trace retrieval was investigated in amygdala (AM), central gray substance of midbrain (CGS) and frontal cortex. There is used the passive avoidance response in the rat. The decrease of 5-HT1 binding sites in AM and CGS was revealed for the rats with retention of the passive avoidance response. The binding of 3H-5-HT in AM was found two sets of binding sites. It was concluded, that 5-HT1 receptors of AM and CGS are involved in learning processes either in the moment of the memory trace retrieval or immediately after it.     

Descending and ascending influences on neurons of the zona incerta

Characteristics of responses of single neurons in zona incerta to electrical stimulation of the amygdala and central gray matter of the midbrain were compared in acute experiments on rats. Analysis of the results showed that stimulation of the central gray matter evokes predominantly excitation (86%), where stimulation of the amygdala invokes inhibition (64%). Convergence of impulses from the amygdala and central gray matter was observed on 58 of 174 responding neurons. Most frequently (57%) the responses were opposite in direction. Stimulation of the amygdala invoked inhibitory effects and stimulation of the central gray matter activation effects. Possible functional relation in the amygdala-zona incerta-central gray matter system are discussed and the role of competitive interactions of flows of impulses descending from the amygdala and ascending from the central gray matter of neurons of zona incerta is examined.Institute of Physiology, Siberian Branch, Academy of Medical Sciences of the USSR, Novosibirsk. Translated from Neirofiziologiya, Vol. 12, No. 1, pp. 46–52, January–February, 1980.     

Iron and Aluminum Increase in the Substantia Nigra of Patients with Parkinson''s Disease: An X-Ray Microanalysis

The levels of different elements were studied by x-ray microanalysis in the substantia nigra and the central gray substance of patients with Parkinson's disease, progressive supranuclear palsy, and matched controls. In control brains, only iron, potassium, silicum, sodium, sulfur, and zinc were within the limit of detection of the technique. The abundance of each element was different, but their respective concentrations in the two brain regions were similar, except for sulfur levels which were higher on neuromelanin aggregates in the substantia nigra than in nigral regions lacking neuromelanin, and in the central gray substance. In Parkinson's disease, but not in progressive supranuclear palsy, nigral iron levels increased in regions devoid of neuromelanin and decreased on neuromelanin aggregates, but were unchanged in the central gray substance, when compared to control values. Concentrations of the other elements in the central gray substance and substantia nigra were not different from controls in brains from patients with Parkinson's disease and progressive supranuclear palsy. Analysis of Lewy bodies in the parkinsonian substantia nigra revealed high levels of iron and the presence of aluminum. Metal abundance was not affected in progressive supranuclear palsy, in spite of the nigral cell death. This suggests that the increased iron levels and the detection of aluminum observed in Parkinson's disease are not solely the consequence of the neuronal degeneration.     

Substance P in the central mechanisms of the escape reaction

The role of substance P in the central mechanisms of escape reaction elicited by electrical stimulation of the ventromedial hypothalamus was investigated in chronic experiments on rabbits. Intravenous injection of substance P (30 micrograms/kg) led to a short-term (less than 10 min) increase in the threshold of stimulation of the ventromedial hypothalamus and to more stable (up to 1.5 h) disorders of the hippocampal-hypothalamic relations. After substance P injection the inhibitory effects of the dorsal hippocampus but not the facilitating influences of the midbrain reticular formation on excitability of the hypothalamic motivation center were found to be lacking. Disorders of the central mechanisms of escape reaction after substance P injection correlated with new patterns of the main EEG rhythms in different areas of the brain cortex in response to the ascending excitations of the limbic-midbrain structures. Interpreting the mechanisms of substance P involvement in escape reaction the authors point to the ability of the given peptide to interact with different transmitter systems of the brain and opiate receptors and to alter the brain blood circulation.     

Substance P and the ethanol-evoked changes in the independent motivated behavioral reactions of rabbits

Ethanol (0.5 g/kg) administered intravenously led to alterations in central mechanisms of feeding and escape, elicited by threshold electrical stimulation either of lateral or of ventromedial hypothalamic centers of the rabbit. Subsequent intravenous injection of substance P (30 mcg/kg) restored the excitability of the ventromedial hypothalamus and facilitatory effects on this motivational center of the midbrain reticular formation. The restoration of both inhibitory influences of the dorsal hippocampus and facilitatory ones of the midbrain reticular formation on the excitability of the lateral hypothalamus was also observed after SP administration. Data obtained suggest that oligopeptides could be used to increase the tolerance to ethanol or to cure the negative acute effects of alcohol in motivated behaviours.     

Enhancement of the resistance of the escape reaction to ethanol after substance P]

An ability of substance P (30 micrograms/kg intravenously) to prevent deleterious effects of ethanol (E) (0.5 g/kg intravenously) on central mechanisms of escape reaction elicited by threshold electrical stimulation of the ventromedial hypothalamus was investigated in chronic experiments upon rabbits. Substance P was found to prevent E effects on excitability of the ventromedial hypothalamus (VMH) and on facilitatory influences of the midbrain reticular formation on this emotional centre which were observed in intact animals. Inhibitory effects of the dorsal hippocampus on the VMH could not be evaluated due to its alterations in response to previous substance P administration. The authors suggest that substance P can be considered to be a possible endogenous factor to increase a tolerance of emotional behavioural reactions of an organism to alcohol.     

Effects of aspartate,substance P,and serotonin on neuronal activity in the central gray substance:In vitro experiments

Effects of aspartate (2 · 10^–5 M), substance P (10^–7–10^–8 M), and serotonin (5-hydroxytryptamine, 5-HT; 5 · 10^–5 M) on the background activity of neurons in the central gray substance (CGS) were studied on slices of the rat midbrain. Aspartate and substance P (transmitters of nociceptive signals), and 5-HT (modulator of transmission of nociceptive influences) were found either to facilitate or to depress the activity of CGS neurons. The predominant effect of substance P or 5-HT applications to neurons of the dorsal CGS part was facilitation, and to neurons of the ventral CGS part, inhibition. The effects of aspartate application on studied CGS neurons were of varying nature, but inhibitory effects were found to prevail.The findings support our earlier hypothesis that assigned the studied neurons to spontaneously discharging inhibitory CGS interneurons, which control the activity of efferent CGS neurons. The role of tested substances in the regulation of CGS neuronal activity and the antinociceptive CGS effects is discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 5, pp. 354–362, September–October, 1993.     

Distribution and quantitative characterization of NADPH-diaphorase-reactive neurons in analgesic zones of the rat midbrain

The distribution of nitric oxide synthase (nicotinamide adenine dinucleotide phosphate diaphorase, NADPH-d)-containing neurons in the rat midbrain was studied. We found that NADPH-d-reactive neurons were predominantly concentrated in the dorsolateral part of the periaqueductal gray (PAG) and the dorsal raphe nucleus, which are implicated in the control of nociceptive transmission. Such neurons were also present in the supraoculomotor cap and laterodorsal tegmental nuclei. In the dorsolateral part ofPAG, the moderately stained small fusiform cells were revealed. In the dorsal raphe nucleus and laterodorsal tegmental nuclei, the densely stained multipolar or oval cells of larger size dominanted. The NADPH-d-reactive cells were not found in the ventrolateral part of central gray, which is considered the main source of antinociceptive descending influences. Quantitative analysis of histochemically revealed neurons showed that their number is somewhat higher in the caudal parts of dorsolateral central gray and considerably higher in the rostral regions of some dorsal raphe subnuclei. This peculiarity was expressed in significant accumulation of the NADPH-d-reactive neurons at the midbrain levels from Fr –7.6 to –8.0. The possible involvement of the NO-synthase-containing class of neurons in the functional organization of analgesic zones and formation ofPAG antinociceptive output signals is discussed.Neirofiziologiya/Neurophysiology, Vol. 28, No. 1, pp. 36–46, January–February, 1996.     

5-HT1 receptors in rats with amnesia

5-HT1 receptors of the amygdala, midbrain's central gray substance, hippocampus and frontal cortex of the rats were investigated during the memory trace retrieval, using the model of "psychogenic" amnesia. It was found that specific binding of 3H 5-HT in amygdala and central gray substance was decreased in the rats with passive avoidance retention. 3H 5-HT binding in the amnesic rats didn't differ from the control animals. Absence of decrease of 5-HT1 receptors number could be considered as one of the possible mechanisms of the memory trace non-retrieval due to amnesia or its consequence.     

A contributory role for midbrain progesterone in the facilitation of female sexual behavior in rats

Progesterone (P) facilitation of sexual receptivity in rodents has been achieved by intracranial administration to the ventral hypothalamus; the preoptic area; and midbrain areas such as central gray, mesencephalic reticular formation, and ventral tegmental nucleus. In our laboratory, by far the most effective site in rats has been the ventromedial nucleus of the hypothalamus (VMN). However, several reports of sensitivity to P in the midbrain of rats and other rodent species led us to investigate whether stimulation of the ventral midbrain of female rats might contribute to facilitation of sexual receptivity. Ovariectomized Long-Evans rats received one cannula aimed at the VMN, and another aimed at the contralateral ventral mesencephalon. P in both cannulae, following a priming dose of estradiol, caused significantly higher lordosis quotients (LQ) than blank tubes. Controls with bilateral cannulae in the VMN responded when both tubes were filled with P, but did not respond to unilateral VMN P stimulation. P in the VMN and contralateral anterior preoptic area did not result in a greater degree of receptivity than did the empty tubes. These studies indicate that although progesterone stimulation in the midbrain alone is not sufficient to facilitate receptivity in female rats with our methods, the midbrain may play an auxiliary role. P implants in the midbrain appear to facilitate receptivity in the case of VMN implant treatments that are subthreshold for stimulating lordosis. The results are discussed in light of similar studies in other rodent species, and in the context that more than one brain site may be important in the natural stimulation of sexual receptivity by gonadal hormones.     

Changes in the arterial pressure and evoked potential in the sensorimotor cortex induced by nalorphine injected in the hypothalamus during painful electric shock in rabbits

During the hypotensive phase of electronocuous shock in rabbits, injection of nalorphine to the hypothalamus provoked elevation in the blood pressure (BP), recovery of the evoked potential (EP) of the sensorimotor brain cortex in response to electrodermal stimulation (EDS) of the hind limb. Injection of the drug to the central gray of the midbrain resulted in an insignificant short-term elevation of the BP followed by its drop. It is concluded that the endogenous opioid system of the hypothalamus is of importance in the genesis of the hypotensive response and suppression of the EP of the rabbit sensorimotor brain cortex in response to EDS during electronocuous shock.     

Adrenomedullary secretory response to midbrain stimulation in rat: effects of depletion of brain catecholamines or serotonin

Electrical stimulation of the periaqueductal gray substance (PAG) of the rostral midbrain of the rat produced biphasic or monophasic pressor responses depending on the duration of the stimulus train. Marked increases in plasma noradrenaline (NA) and adrenaline (A) levels accompanied the pressor responses, indicating the participation of the adrenal medulla. Depletion of central catecholamines (CA) by intraventricular administration of 6-hydroxydopamine (6-OHDA) did not affect the primary vasomotor component but markedly depleted adrenal CA levels and attenuated the adrenomedullary component of the response to brain stimulation. The intraperitoneal administration of p-chlorophenylalanine (pCPA) not only depleted brain serotonin (5-HT) levels but also reduced brain CA levels significantly. The adrenaline (A) levels were reduced in the adrenal glands of these rats and the adrenal secretory response to brain stimulation was attenuated. In contrast, the selective destruction of central 5-HT neurons by intraventricular injection of 5,7-dihydroxytryptamine (5,7-DHT) in rats pretreated with desmethylimipramine (DMI) did not influence either the pressor nor the plasma CA responses to brain stimulation. Furthermore, the adrenal glands of these rats were normal. The results suggest that: (i) the central catecholaminergic neurons play an important role in the regulation of the adrenal glands but are not essential for the activation of the sympathetic vasoconstrictor fiber system: (ii) the pressor and plasma CA responses to PAG stimulation are not dependent on the central serotonergic system.     

Effect of substance P on catecholamine levels in the hypothalamus and midbrain in the rat during immobilization stress

Single intraperitoneal injection of substance P in a dose of 125 mcg/kg induced a significant increase of noradrenaline and dopamine level in the hypothalamus and the midbrain of intact rats. Under conditions of immobilization emotional stress, the substance P eliminated the stress induced decrease of hypothalamic noradrenaline and increase of its level in the midbrain; in other words the substance P normalized the noradrenaline level. Modulatory effect of a single injection of the substance P had a long-term character and was synchronized with an earlier found increase of resistability of rats to chronic emotional stress.     

The distribution of alpha-melanocyte stimulating hormone (alpha-MSH) in the central nervous system of the rat: an immunohistochemical study. II. Lower brain stem

The distribution of immunoreactive alpha-melanocyte stimulating hormone (alpha-MSHI) in the rat lower brain stem was examined by indirect immunofluorescence or peroxidase- anti-peroxidase immunohistochemical method using an antiserum against synthetic alpha-MSH. The results confirmed the presence of alpha-MSHI fibers in the midbrain central gray matter and parabrachial area, and demonstrated a much more extensive distribution of these fibers in various parts of the lower brain stem areas previously thought not contain alpha-MSHI fibers. In addition, the commissural nucleus was identified as a new alpha-MSHI neurons-containing site. No alpha-MSHI neurons were seen in other regions of the rat lower brain stem.     

Mammal-like organization of the avian midbrain central gray and a reappraisal of the intercollicular nucleus

In mammals, rostrocaudal columns of the midbrain periaqueductal gray (PAG) regulate diverse behavioral and physiological functions, including sexual and fight-or-flight behavior, but homologous columns have not been identified in non-mammalian species. In contrast to mammals, in which the PAG lies ventral to the superior colliculus and surrounds the cerebral aqueduct, birds exhibit a hypertrophied tectum that is displaced laterally, and thus the midbrain central gray (CG) extends mediolaterally rather than dorsoventrally as in mammals. We therefore hypothesized that the avian CG is organized much like a folded open PAG. To address this hypothesis, we conducted immunohistochemical comparisons of the midbrains of mice and finches, as well as Fos studies of aggressive dominance, subordinance, non-social defense and sexual behavior in territorial and gregarious finch species. We obtained excellent support for our predictions based on the folded open model of the PAG and further showed that birds possess functional and anatomical zones that form longitudinal columns similar to those in mammals. However, distinguishing characteristics of the dorsal/dorsolateral PAG, such as a dense peptidergic innervation, a longitudinal column of neuronal nitric oxide synthase neurons, and aggression-induced Fos responses, do not lie within the classical avian CG, but in the laterally adjacent intercollicular nucleus (ICo), suggesting that much of the ICo is homologous to the dorsal PAG.