Septal nuclei in the regulation of vago-sensitive neurons activity of the solitary nucleus in cats

The descending influences of the septal nuclei (lateral nucleus--LSN and bed nucleus stria terminalis--BNST) on activity of viscero-sensory neurons of the nucleus of tractus solitarius (NTS) identified by stimulation of cervical part of the n. vagus were investigated in the cat anaesthetised by chloraloze-nembutal combination. It was found that out of 70 units recorded in the NTS area 50 were identified as those of primary and secondary input vagal neurons. Influence of single, paired and frequency stimulation on the septal structures was studied on these neurons. It was revealed that 30% (15 un) reacted by phase-specific response to the single stimulation of the septal nuclei. The latent period of initial excitation was in the range 5-25 ms. During the paired stimulation these neurons were not able to react to the second stimulus for the equal 10-300 ms. It was revealed that 34% (17 un) of the identified vagal neurons reacted by a tonic change of their spontaneous activity. The increase of frequency stimulation to 20 Hz evoked different changes of the rhythmical activity of the vagal neurons (increase, diminishing or inhibition). The study of interaction between central and peripheral signals in the solitary neurons induced blocking influence of descending septal discharge on the vagal test response. It is possible that the septal downward impulses reach the vago-sensitive solitary neurons indirectly through other structures of the limbic brain (amygdala, hypothalamus) and participate in modulation of the spontaneous activity of these neurons.     

Modulation by arginine vasopressin of glutamate excitation in the ventral septal area of the rat brain

Arginine vasopressin is hypothesized to act as a neurotransmitter or neuromodulator in the ventral septal area of the rat brain. To examine this role of vasopressin further, it was applied by microiontophoresis or micropressure from multiple-barrelled micropipettes onto spontaneously active or glutamate-activated neurons. Applied in this manner, vasopressin reduced glutamate-evoked excitation in 32 of the 47 cells studied. Further, micropressure application of the vasopressin antagonist d(CH2)5Tyr(Me)AVP reversed the vasopressin effects. In contrast, administration of vasopressin had no effect on excitations evoked by acetylcholine iontophoresis or on the spontaneous activity of the majority of the ventral septal neurons studied. These observations suggest that vasopressin may be acting on a V1-like receptor on specific neurons in the ventral septal area as a modulator of glutamate actions. Evoked responses were also obtained in the same population of ventral septal cells following stimulation of a variety of limbic areas. Inhibitory input onto most of the vasopressin responsive neurons studied was obtained following electrical stimulation of the paraventricular nucleus and bed nucleus of the stria terminalis, two cell groupings that are potential sources of vasopressin to the ventral septal area. Thus, the similarity in action of exogenously applied vasopressin and the evoked responses following paraventricular nucleus and bed nucleus stimulation suggests that vasopressin may be a neurotransmitter in this pathway.     

Effect of electrical stimulation of the septum on subicular neurons with different kinds of spontaneous activity in rabbits

The effect of electrical stimulation of the medial nucleus of the septum and of hippocampal area CA₁ on subicular neurons with three different types of spontaneous activity (with theta-modulation, with delta-modulation and complex spikes, and with irregular single-spike activity) was studied in unanesthetized rabbits by extracellular recording of unit activity. Cells with theta-activity were found to respond in a distinctive functional manner to stimulation of the medial nucleus of the septum: Their reactivity was higher but latent periods of their responses were much shorter than those of cells with delta-activity and irregular discharges. Stability of modulation of theta-cell activity increased both during and after stimulation of the medial septal nucleus. Electrical stimulation of hippocampal area CA₁, on the other hand, led to disappearance of rhythm modulation. Average response latencies of all three types of cells to stimulation of area CA₁ were equal. The results indicate special properties of the septal input to subicular cells with theta-modulation.Institute of Biological Physics, Academy of Sciences of the USSR, Pushchino-on-Oka. Translated from Neirofiziologiya, Vol. 17, No. 3, pp. 326–333, May–June, 1985.     

家兔隔核中去甲肾上腺素对皮肤与内脏痛阈的影响

本工作以电刺激内脏大神经或耳尖部皮肤测定清醒家兔内脏痛阈或皮肤痛阈,以探讨隔核去甲肾上腺素在内脏镇痛和皮肤镇痛中的作用以及与中脑导水管周围灰质(PAG)中内阿片肽系统的关系。实验观察到,双侧隔核内微量注射α受体激动剂可乐宁(10μg/2μl)或α受体阻断剂酚妥拉明(10μg/2μl)对内脏痛阈无明显影响。注入β受体激动剂异丙肾上腺素(1μg/2μl)使内脏痛阐明显升高;而注入β受体阻断剂心得安(1Cμg/2μl)则内脏痛阈明显降低。隔核内注入酚妥拉明(10μg/2μl)或心得安(10μg/2μl)均可使皮肤痛阈明显提高。提示,隔核内NA通过β受体调制内脏痛;通过α受体和β受体调制皮肤痛。隔核内注入异丙肾上腺素(1μg/2μl)明显地镇内脏痛,此作用可被PAG内注射纳洛酮(1μg/2μl)或注射抗亮啡肽抗血清(1:20,000)所减弱;但可使PAG内亮啡肽样物质释放量增加。这提示,隔核内NA的镇内脏痛作用与PAG的内阿片肽系统有关;其中亮非肽在这一过程中具有重要作用。     

电刺激大鼠尾核头部镇痛的中枢效应—[^3H]—2脱氧...

Sokoloff's 2-deoxyglucose (2-DG) autoradiographic technique was used to identify changes of glucose metabolic rate in the rat brain following unilateral stimulation of the head of the caudate nucleus. The results were as follows. The local glucose metabolic rate after noxious stimulation was increased in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area, habenular nucleus, head of caudate nucleus, periaqueductal gray (PAG) and dorsal raphe nucleus (P < 0.05). After stimulating the head of the caudate nucleus, the local glucose metabolic rate of nucleus raphe magnus (rm) and nucleus paragigantocellularis (pgcl) was increased significantly and that of the PAG and dorsal raphe nucleus had a tendency to increase, while stimulation of the head of caudate nucleus could partially abolish the increased glucose metabolic rate in the somatosensory cortex, cingulate cortex, ventroposterior and parafascicular nucleus of the thalamus, septal area and habenular nucleus as induced by noxious stimulation. These results suggest that caudate stimulation is able to depress the activation of some brain structures related to nociception and to activate those related to antinociception. The pgcl, rm, PAG and dorsal raphe nucleus might be the key structures participating in the caudate stimulation produced analgesia.     

Modulation of neuronal evoked responses to the medial septal area of hibernating ground squirrels by some neuropeptides after chronic disconnection between septum and preoptico-hypothalamic structures

Effects of some neuropeptides identified in the brain of hibernators (TSKYR, TSKY, DY) and of monoaminergic neurotransmitters (noradrenaline and serotonin) on responses of the medial septal neurons evoked by intraseptal electrical stimulation were analyzed in slices taken from the ground squirrels with chronic basal undercutting of the septum. Despite the elimination of direct contacts with the preoptic area and afferents ascending in the medial forebrain bundle, the neurons retained almost normal level of reactivity and distribution of the reaction types. The neuropeptides effectively modulated neuronal responses of various types, including oligosynaptic short-latency single-spike responses. The latter were strongly facilitated by the neuropeptides. As a rule, changes in the responses to electrical stimulation were independent of the spontaneous activity shifts (in 78% of the tests). It was suggested that the neuropeptides exert a double influence on the septal neurons: direct nonsynaptic effects on the pacemaker potential responsible for the background activity and modulation of synaptic processes. Our experiments showed that descending influences of the septo-hippocampal system are not crucial for the entrance into the hibernation state and its tonic maintenance. The influences of the thermoregulatory--circadian structures of the preoptico-hypothalamic area determine the paradoxically increased latent excitability of septal neurons that allows the septo-hippocampal system to gate external stimuli and organize arousal of the forebrain during hibernation in case of emergency.     

Septal neurons related with hippocampus increase their firing rate after long-term clomipramine.

In the rat, long-term clomipramine increases the firing rate in lateral septal neurons. Although the hippocampus is the main afference for septal nuclei, it is unknown whether clomipramine increases the firing rate in most of hippocampal-septal neurons. Therefore, the present study explored the actions of long-term clomipramine in lateral septal neurons identified by their relation to the hippocampus. In most recordings, hippocampal stimulation produced a brief excitatory short-latency response, followed by a period of inhibition of firing. These neurons increased their firing rate after clomipramine treatment. Other septal neurons not respondent to hippocampal stimulation did not respond to clomipramine treatment, either. We concluded that only hippocampal-septal neurons are clomipramine responders too, and the drug-induced enhancement of firing rate is likely to be mediated by an interneuron-mediated disinhibition process.     

Negative occurrence between hippocampal rhythmic slow activity and epileptiform spikes: influence of the striatum

The effects of caudate and septal stimulation on hippocampal activity were studied. Sodium penicillin was intravenously injected in order to induce a steady rate of interictal epileptic activity. Penicillin injection caused significant reduction of the rate of occurrence and duration of hippocampal rhythmic slow activity (RSA). Spontaneous RSA as well as RSA-eliciting caudate and septal stimulation induced a marked inhibition on frequency of epileptiform complexes. Lesions of the medial septal nucleus made it impossible to record RSA or to observe any sort of influence on hippocampal epileptiform activity by caudate stimulation. This result suggests that the septum is important for RSA genesis in the striato-hippocampal pathway or in the reciprocal septo-hippocampal connections.     

Comparative characteristics of septal "burst" neurons after elimination of afferent effects of the reticular formation in the rabbit

Comparative analysis of characteristics of rhythmic theta-activity in the neurones of the medial septal nucleus and nucleus of diagonal band was performed in intact rabbits after. i. v. injection of pentobarbital, and in rabbits with chronic lesion of the ascending brain-stem afferent fibers. In both conditions theta-bursts disappeared in some cells with unstable periodic rhythmic modulation; substantial population of the septal units preserved regular burst activity. Main characteristics of theta-bursts were almost identical in both states, their mean frequency decreased to 3.5 Hz. The theta-rhythm in hippocampal EEG was usually absent; but low-frequency rhythmic activity could be evoked by electrical or sensory stimulation as well as by injection of bemegrid or physostigmine. The data show that the ascending brain-stem afferents control: the frequency of the bursts in a population of septal units regarded as bursting pace-maker cells; the total number of the septal cells secondarily (synaptically) involved into rhythmic activity. The effect of pentobarbital upon theta-rhythm results from elimination of these influences upon the septal cells.     

Mechanism of the analgesic effect of narcotic analgetics]

A study was made of the effect of morphine, promedol, phentanyl, pentazacine and psychostimulant d,l-amphetamine on the threshold of pain sensitivity and self-stimulation of the hypothalamus and the septum in rats. Electrical stimulation of the systems of positive reinforcement of the hypothalamus and the septum, and also analgetics increased the threshold of pain sensitivity, whereas d,l-amphetamine failed to influence it. D,l-amphetamine and morphine facilitated, promedol failed to influence, phentanyl decreased and pentazacine completely depressed the hypothalamic self-stimulation. The septal self-stimulation remained unaltered under the effect of morphine, promedol, phentanyl, but was decreased under the effect of pentazacine and increased against the background of d,l-amphetamine. A conclusion was drawn that the analgetic action and that activating the positive emotion were independent effects of the psychotropic agents.     

电刺激大鼠尾核头部镇痛的中枢效应——〔~3H〕-2脱氧葡萄糖放射自显影研究

本文利用[~3H]-2脱氧葡萄糖定量放射自显影方法,研究了电刺激大鼠尾核头部镇痛时中枢神经系统有关结构的葡萄糖代谢率变化。结果表明,痛刺激后,皮层躯体感觉Ⅰ,Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、尾核、外侧缰核、外侧隔核、中缝背核及中脑导水管周围灰质等结等的葡萄糖代谢率均明显升高(P<0.05)。电刺激大鼠尾核头部后,中缝大核及延髓旁巨细胞网状外侧核的葡萄糖代谢率显著升高,中脑导水管周围灰质和中缝背核的葡萄糖代谢率亦有升高趋势。电刺激大鼠尾核头部可部份降低痛刺激引起的有关结构葡萄糖代谢率升高(如皮层躯体感觉Ⅰ、Ⅱ区、扣带回皮质、丘脑束旁核、丘脑中央中核、丘脑腹后核、外侧隔核及外侧缰核等)。上述结果提示,电刺激大鼠尾核头部镇痛时抑制了与痛感觉有关的结构,同时激活了与镇痛有关的结构。中缝大核、中缝背核、中脑导水管周围灰质及延髓旁巨细胞网状外侧核等结构是实现尾核镇痛的重要环节。     

Mechanisms of the regulation and functional significance of the theta rhythm. Roles of serotonergic and noradrenergic systems

The evidence for the role of serotonergic and noradrenergic effects on the septohippocampal theta oscillations obtained by the author and her colleagues are reviewed. Analysis of neuronal activity in the medial septal area or hippocampus and hippocampal EEG simultaneously recorded in awake rabbits exposed to different kinds of brainstem influences led to the following conclusions. 1. Serotonergic median raphe nucleus and noradrenergic locus ceruleus act as functional antagonists in theta regulation: the former structure restricts the theta rhythm generation, whereas the latter enhances this process. 2. Both transmitter systems control sensory reactions of septal and hippocampal neurons through up and down regulation of the theta activity. 3. When continuous theta activity induced by various experimental manipulations is recorded, responsiveness of septohippocampal neurons to sensory stimulation is strongly reduced. These findings provide support for the view that the theta oscillations act as an active filter in the information selection and registration. Interaction of different transmitter systems in the theta rhythm control as well as attention and memory is discussed.     

Reactions of neurons in the dental projection area of the rabbit sensomotor cortex to photic, acoustic and painful stimulation of the dental pulp]

In experiments on unrestrained rabbits interactions of sound (tone, click), light and pain excitation occurring during stimulation of the dental pulp in the neurons of the cortical sensomotor zone, in the area of representation of the dental afferents were studied by the microelectrode method. It was shown that bi- and polysensor convergence of excitation is realized in the cells of this area. It is suggested that convergence of excitation underlies the mechanisms of formation of the integral systemic pain reaction during stimulation of the dental receptors.     

Theta driving both inhibits and potentiates the effects of nicotine on dentate gyrus responses

The medial septal area of conscious rats was stimulated through previously implanted electrodes at a frequency of 7.7 Hz for 20 min each day for 7 days to evoke rhythmic slow activity in CA1 at a similar frequency to spontaneous theta. Two weeks later in the anaesthetized rats the effects of a single subcutaneous injection of nicotine (0.4 mg x kg(-1)) on fEPSPs, evoked in the dentate gyrus by separate stimulation of the MPP and LPP, were studied and compared with those obtained in controls. Nicotine increased the firing of locus coeruleus neurones and the slope of the fEPSPs evoked by LPP stimulation, but not by MPP stimulation. Prior theta driving considerably increased the effect of nicotine on the responses evoked by stimulation of the MPP and abolished the nicotine-induced potentiation of the responses evoked by stimulation of the LPP. The results are attributed to theta driving increasing the amount of noradrenaline released by nicotine and to noradrenaline producing a beta-adrenoceptor long-lasting potentiation at the medial perforant path synapse and a long-lasting depression at the lateral perforant path synapse.     

Septal nuclei in the mechanisms of lateral hypothalamic self stimulation in rabbits

Unilateral lesions of medial septal nucleus and lateral septal nuclei (dorsalis, intermedius, ventralis) decreased ipsilateral hypothalamic self-stimulation; the lesions of n. dorsalis, n. medialis and lateral septal nuclei (intermedius and ventralis) has the opposite effect on contralateral self-stimulation. The inhibition of ipsilateral self-stimulation was neither total nor permanent; 25-32% decrease in stimulation rate was seen, but behaviour returned to near-normal levels over a period of few days. In contrast, the augmentation of contralateral self-stimulation showed no significant change over the same period; in this case the 35-40% shift in stimulation rate was immediate and permanent. Bilateral lesions of septal nuclei had no effect if the initial level of self-stimulation rate was high and significantly increased self-stimulation.     

Hexamethonium, nicotinic receptor blocker, changes the neuronal reactions on glutamate in the medial septal area in vitro

Despite the great interest in studying the medial septal area, the interactions of its neurochemical systems are not yet clearly understood. The aim of this study was to elucidate the role of nicotinic receptors in the interaction of glutamatergic and cholinergic systems of the medial septal area. The effect of L-glutamate (1 microM) on septal neurons was studied under the application of hexamethonium, nicotinic cholinoreceptor blocker by using the method of extracellular recording of neuronal activity in brain slices of ground squirrels. The response of septal neurons to glutamate depended on the type of their initial activity and on the presence of pacemaker properties. For the first time, the ability of septal neurons to respond to glutamate with an increase in burst frequency was shown. The influence of hexamethonium on the neuronal activity was similar to that of glutamate. After a preliminary application of hexamethonium, the reactions of neurons to glutamate changed. The excitatory reactions were masked, while the inhibitory reactions became stronger. It was found that nicotinic cholinergic receptors modulated the reactions of MS-DB cells to glutamate and the expression of the oscillatory properties of the septal neuronal network.     

The influence of damage to the septum pellucidum on the effects of electrical stimulation of the hypothalamus in rabbits]

In chronic experiments the influences of septal lesions on the behavioural emotional effects of electrical stimulation of various hypothalamic nuclei were investigated. The total ablation of the septum caused irreversible increase of the lateral hypothalamus self-stimulation and reversal of the negative emotional responses (escape--avoidance) to the medial hypothalamus stimulation into the positive self-stimulation behaviour. When the septal ablation was only partial, involving mainly the medial nucleus, effects were weaker and lasted only 2-3 days after the surgery. The role of the septum in the septohippocampal behavioural inhibition system (J. Gray) is discussed.     

Evidence for antipyretic vasopressinergic pathways and their modulation by noradrenergic afferents.

The experimental evidence for the antipyretic action of arginine vasopressin (AVP) in guinea-pigs can be summarized as follows: The febrile response to a bacterial pyrogen can be reduced by a microinfusions of exogenous AVP into the ventral septal area of the limbic system. Immunohistochemical studies indicate increased activity of AVP terminals in the ventral septal area (VSA) and in parvocellular AVP neurones of the hypothalamic paraventricular nucleus (PVN) in several stressful situations accompanied by reduced febrile responses (late stage of pregnancy, immobilization, cold adaptation, osmotic stimulation). Also the peripheral and/or central release of AVP measured in some of these situations is increased. Electrical stimulation of the PVN suppresses fever, this suppression can, at least partly, be cancelled by simultaneous intraseptal application of the vasopressinergic V1 receptor antagonist. The documented AVP pathways from the PVN to the septum receive noradrenergic afferents from the lower brainstem. Chronic destruction of these afferents by microinjections of 6-hydroxydopamine (6-OHDA) significantly reduced the fever responses to pyrogen application, while microinfusion of noradrenaline (NA) enhances the fever reaction.     

Growth of a graft from the septal region of the brain in the anterior chamber of the eye

The neural tissue (the hippocamp and septal cerebral area) obtained from rat embryos is transplanted into the anterior eye chamber of mature animals. The developing grafts are sized and measured and light optic microscopy is performed 3-4 months after transplantation. Essential differences in development and organization of the septal cerebral area (SCAG) and the hippocampal (HG) grafts are revealed. The SCAG have a spherical form, a limited contact with the host iris and are vascularized by one--two ingrowing and branching vessels. The HG are elongated in their form, have contacts with the host iris by the wide plane parallel to their long axis and a great number of blood vessels growing into them. The size of the HG is much larger than that of the SCAG. The latter contain diffusely scattered multipolar neurons, while the HG neurons are organized as a layer with their apical dendrites oriented towards the iris.     

Electrophysiological analysis of septum-amygdala interaction at the level of the dorsomedial thalamic nucleus in the rat

The characteristics were studied of focal potentials and impulse activity of 102 neurones of the thalamus dorsomedial nucleus (DMN) of anaesthetized rats under stimulation of the anterior periamygdalar cortex (APC) and septal lateral nucleus (SLN). The dominating type of impulse responses to APC and SLN stimulation recorded correspondingly in 31.4 and 12.8% of cells was expressed in a short latency (10-30 ms) phasic activation. It has been found that the convergence of these inputs, revealed in 9.8% of cells, is unidirected according to the genotype of the reaction. Neuronal complexes of DMN, organizing the responses to the stimulation of APC and SLN are characterized by a weak interaction testifying to a definite functional differentiation of the amygdalar and septal components of the lymbic-thalamic projection system.