Modulation of spiking of neurons of the cat anterior hypothalamus induced by experimental shifts in the osmolarity of the blood plasma

We examined changes in the impulse activity (IA) generated by neurons of the anterior hypothalamus (including the preoptic region) resulting from infusions of hyper-and hypotonic NaCl solutions (3.0 and 0.2%, respectively; hyper-and hypoosmotic stimulations, respectively); the infused volumes did not exceed 200 μl. The effects of hyper-and hypoosmotic stimulations were studied in detail in 83 and 88 neurons, respectively. In 31.2% (26 cells) and 29.6% (26 cells) of the neurons of the above groups, these stimulations evoked changes in the IA frequency greater than +40 or −40% of the mean background IA frequency. In approximately 50% of the responding neurons in each group, such shifts in the IA frequency were observed in the course of infusions of test solutions (5 sec long) and within the subsequent 5 min after termination of the infusion. In another 50% of the neurons, changes in the IA frequency occurred within the afterperiod (30 sec long); these shifts could develop exclusively within the latter interval, or these changes accompanied an initial early reaction. In general, activating responses dominated (they were observed in 65% of the cases where test stimulations of both modalities were used). The possible aspects of the involvement of neurons of the anterior hypothalamus in the control of the water/salt balance in the organism are discussed. Neirofiziologiya/Neurophysiology, Vol. 38, No. 1, pp. 40–45, January–February, 2006.     

Modifications of neuronal activity in the rat hypothalamic supraoptic nucleus after long-lasting vibrational stimulation

We analyzed the background impulse activity (BIA) generated by neurons of the rat hypothalamic supraoptic nucleus in the norm and under conditions of long-lasting vibrational stimulation (exposure 5, 10, or 15 days). Distributions of neurons by the level of regularity, dynamics of discharge trains, form of histograms of interspike intervals (ISIs), as well as distributions of neurons by the BIA frequency ranges, were studied. We also calculated the mean frequency of impulsation of the neurons under study and the coefficient of variation of ISIs. After vibrational influences, we found modifications of both the internal structure of the recorded spike trains and the mean frequency of impulsation within the entire studied group and different frequency subgroups. Neirofiziologiya/Neurophysiology, Vol. 38, No. 3, pp. 224–230, May–June, 2006.     

Background activity of neurons of the supraoptic hypothalamic nucleus in rats under conditions of vibrational stimulation and electromagnetic extrahigh-frequency irradiation

We analyzed background impulse activity of neurons of the supraoptic nucleus of the rat hypothalamus in the course of 15-day-long isolated action of generalized vibrational stimulation and combination of such stimulation with irradiation of the animal’s head with low-intensity extrahigh-frequency (EHF, millimeter-range) electromagmetic waves. The distributions of the neurons by the level of regularity and dynamics of spike trains, separate frequency ranges of impulsation, and pattern of interspike interval (ISI) histograms were estimated. We also calculated the mean frequency of discharges and coefficient of variation of ISIs. A trend toward decreases in the deviations of some parameters of neuronal spike activity generated by supraoptic neurons, which were evident within early time intervals of isolated action of vibration (5 to 10 days), was observed under the influence of EHF electromagnetic irradiation; thus, the latter factor probably exerts a sedative effect. Neirofiziologiya/Neurophysiology, Vol. 39, No. 6, pp. 433–442, November–December, 2007.     

Dynamics of the background impulse activity of neurons of the lateral vestibular nucleus in the norm and under vibrational influence

The background impulse activity (BIA) generated by neurons of the right lateral vestibular nucleus (LVN) of rats in the norm and under conditions of long-lasting general vibrational stimulation was subjected to computer analysis. Statistically significant changes in intragroup values of the mean BIA frequency were observed after 5 and 10 days with 2-h-long sessions of vibrational stimulation. Significant shifts in the distributions of LVN neurons by the level of regularity and dynamic types of BIA were observed 10 and 15 days with vibrational influences. Trends toward return of the intragroup mean value of the BIA frequency to the initial level were noticeable at the end of the stimulation period (15 days). Neirofiziologiya/Neurophysiology, Vol. 37, Nos. 5/6, pp. 424–431, September–December, 2005.     

Background impulse activity of neurons of the fastigial cerebellar nucleus of intact and labyrinthectomized rats under conditions of vibration

In acute experiments on nembutal-anesthetized (40 mg/kg, i.p.) albino rats, we recorded extracellularly and analyzed the background impulse activity (BIA) of neurons of the fastigial nucleus of the cerebellum. Experiments were carried out on intact and labyrinthectomized rats in the norm and after long-lasting (up to 15 days) influence of general vertical vibration (60 Hz, 0.4 mm, 2-h-long everyday sessions). Distributions of the neurons according to the level of regularity of BIA, dynamics of spike trains, pattern of histograms of interspike intervals (ISIs), and different frequency ranges of BIA were plotted; the mean frequency of this activity and the coefficient of variation of ISIs were also calculated. Possible mechanisms of the effects of long-lasting vibration of different durations on the BIA generated by neurons of the fastigial cerebellar nucleus in intact animals and after switching off of labyrinth afferent inputs are discussed. Neirofiziologiya/Neurophysiology, Vol. 38, No. 1, pp. 32–39, January–February, 2006.     

Effects of acoustic and immobilization stress on background impulse activity of neurons of the central and lateral nuclei of the Amygdala

It was shown that acoustic and immobilization stresses (developed due to a 2.5-h-long session of intensive, 100 dB, acoustic influence and a 2-h-long session of soft fixation of the body and extremities, respectively) result in significant modifications of the characteristics of background impulse activity of neurons of the nuclei of the rat amygdalar complex. Modifications were greater in the lateral nucleus of the amygdala. Possible roles of some structures of the monoaminergic cerebral systems in acute stress-related transformations of the impulse activity generated by neurons of the amygdalar complex are discussed. Neirofiziologiya/Neurophysiology, Vol. 38, No. 2, pp. 131–139, March–April, 2006.     

Effects of basolateral amygdalar nuclei on neuronal activity in the medullary respiratory center under hypoxia conditions

The effect of stimulation of the basolateral nuclei of the amygdala (ABL) on the impulse activity of respiratory neurons (RNs) of the rat medulla and the respiratory function was studied in the norm and under conditions of oxygen deficiency. Electrical stimulation of the ABL under conditions of normal atmospheric pressure exerted ambivalent effects on bulbar RNs; both activation and inhibition of these neurons were observed, but inhibitory effects noticeably prevailed. Electrical stimulation of the ABL within an initial phase of hypobaric hypoxia corresponding to ascent to a 4,000 to 5,000 m altitude exerted mostly inhibitory effects on the RN activity (similarly to what was observed under normoxia conditions). Stimulation of these nuclei within a phase of intensive hypoxia (7,500 to 8,000 m) evoked no typical responses of such neurons against the background of hypoxic suppression of their activities. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 292–297, July–August, 2006.     

Involvement of nitric oxide pathways in short term modulation of tyrosine hydroxylase activity by endothelins 1 and 3 in the rat anterior hypothalamus

The ability of endothelins 1 and 3 (ET-1 and ET-3) to reduce neuronal norepinephrine release through ETB receptor activation involving nitric oxide (NO) pathways in the rat anterior hypothalamus region (AHR) was previously reported. In the present work, we studied the effects of ET-1 and -3 on tyrosine hydroxylase (TH) activity and the possible involvement of NO pathways. Results showed that ET-1 and -3 (10 nM) diminished TH activity in AHR and this effect was blocked by a selective ETB receptor antagonist (100 nM BQ-788), but not by a ET(A) receptor antagonist (BQ-610). To confirm these results, 1 microM IRL-1620 (ET(B) agonist) reduced TH activity whereas 300 nM sarafotoxin S6b falled to modify it. N(omega)-Nitro-L-arginine methyl ester (10 microM), 7-nitroindazole (10 microM), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-ona (10 microM), KT5823 (2 microM), inhibitors of nitric oxide synthase, neuronal nitric oxide synthase, NO-sensitive-guanylyl cyclase, and protein kinase G, respectively, did not modify the reduction of TH activity produced by ETs. In addition, both 100 microM sodium nitroprusside and 50 microM 8-bromoguanosine-3',5'-cyclic monophosphate (NO donor and guanosine-3',5'-cyclic monophosphate analog, respectively) diminished TH activity. Present results showed that ET-1 and ET-3 diminished TH activity through the activation of ET(B) receptors involving the NO/guanosine-3',5'-cyclic monophosphate/protein kinase G pathway. Taken jointly present and previous results it can be concluded that both ETs play an important role as modulators of norepinephrine neurotransmission in the rat AHR.     

Effects of ghrelin on neuronal activity in the ventromedial nucleus of the hypothalamus in infantile rats: An in vitro study

Ghrelin is an endogenous ligand for the growth hormone (GH) secretagogue (GHS) receptor (GHS-R) and a potent stimulant for GH secretion even in infantile rats before puberty. Although the ventromedial nucleus of the hypothalamus (VMH) might be a site of action for ghrelin to induce GH release, the electrophysiological effect of ghrelin on VMH neurons in infantile rats remains to be elucidated. Thus, the purpose of the present study was to investigate the effect of ghrelin on VMH neurons using hypothalamic slices of infantile rats. Ghrelin excited a majority of VMH neurons in a concentration-dependent manner. VMH neurons that were excited by GH releasing peptide-6 (GHRP-6), a synthetic GHS, were also excited by ghrelin and vice versa. Repeated application of ghrelin to the same VMH neuron decreased progressively the excitatory responses depending on the number of times it was administered. The excitatory effect of ghrelin on VMH neurons in normal artificial cerebrospinal fluid (ACSF) persisted in low Ca²⁺-high Mg²⁺ ACSF. The present results indicate that (1) ghrelin excites a majority of VMH neurons dose-dependently and postsynaptically and (2) the excitatory effects of ghrelin are mimicked by GHRP-6 and desensitized by repeated applications of ghrelin.     

Structural basis for the catalytic activity of filamentous human serine beta-lactamase-like protein LACTB

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Toxicity and haemolytic activity of a newly described dinoflagellate,Heterocapsa bohainensis to the rotifer Brachionus plicatilis

The algae Heterocapsa bohaiensis is a newly described species of dinoflagellate associated with Penaeus japonicus and larvae of Eriocheir sinensis in a coastal pond of Liaodong Bay China. The rotifer Brachionus plicatilis is used as live feed for aquaculture organisms including prawns and crabs larvae. To evaluate the potential toxicity of H. bohaiensis, the effects on Brachionus plicatilis and haemolytic activity were investigated in this study. The results showed that H. bohaiensis had significant toxic effect on B. plicatilis, and this effect was dependent on the cell concentration. Significant rotifer growth suppression was observed in the ruptured cells of H. bohaiensis with ultrasonic. Relatively similar rotifer mortalities were induced both in the light and in the dark. Interestingly, haemolysis to erythrocytes was also caused in a cell density-dependent and time-dependent manner, which meant the results of haemolytic activity were consistent with the toxicity. Therefore, haemolytic toxins were considered to be involved in the toxic mechanism of H. bohaiensis against rotifers. Then, the concentrations of calcium were measured in the mastax, stomach and ovary of B. plicatilis. Obviously increased fluorescence intensity was found in the stomach, which indicated the alteration of calcium homeostasis and membrane permeability after ingesting H. bohaiensis. These results implicated haemolytic activity as a causative factor linked to the toxicity of H. bohaiensis against B. plicatilis. The results contributed to research the production and control of H. bohaiensis toxins.     

Structural basis of Bacillus anthracis MoxXT disruption and the modulation of MoxT ribonuclease activity by rationally designed peptides

Bacillus anthracis MoxXT is a Type II proteic Toxin–Antitoxin (TA) module wherein MoxT is a ribonuclease that cleaves RNA specifically while MoxX interacts with MoxT and inhibits its activity. Disruption of the TA interaction has been proposed as a novel antibacterial strategy. Peptides, either based on antitoxin sequence or rationally designed, have previously been reported to disrupt the MoxXT interaction but cause a decrease in MoxT ribonuclease activity. In the present study, we report the crystal structure of MoxT, and the effect of several peptides in disrupting the MoxXT interaction as well as augmentation of MoxT ribonuclease activity by binding to MoxT in vitro. Docking studies on the peptides were carried out in order to explain the observed structure activity relationships. The peptides with ribonuclease augmentation activity possess a distinct structure and are proposed to bind to a distinct site on MoxT. The docking of the active peptides with MoxT showed that they possess an aromatic group that occupies a conserved hydrophobic pocket. Additionally, the peptides inducing high ribonuclease activity were anchored by a negatively charged group near a cluster of positively charged residues present near the pocket. Our study provides a structural basis and rationale for the observed properties of the peptides and may aid the development of small molecules to disrupt the TA interaction.     

Identification of a histaminergic circuit in the caudal hypothalamus: An evidence for functional heterogeneity of histaminergic neurons

It is well established that histaminergic neurons in the posterior hypothalamus make connections with whole brain areas and regulate several functions. Recent evidence indicates that histaminergic neurons are heterogeneous cell group and organized into distinct circuits. However, functional circuits of histaminergic neurons have not been fully mapped so far. To address this issue, we have investigated antihistamine-sensitive neuronal activation in the hypothalamus to determine the hypothalamic region primarily innervated by histaminergic neurons. Here we review our recent findings showing the existence of the heterogeneous subpopulations of histaminergic neurons in the TMN that innervated distinct regions to regulate particular functions. We have identified the caudal part of the arcuate nucleus of hypothalamus (cARC) as a target region of histaminergic neurons in food-restricted rats by assessing suppression of c-Fos expression by pretreatment with antihistamines. Histaminergic neurons in the tuberomammillary nucleus (TMN) are morphologically subdivided into five groups (E1–E5). Among the subdivisions, the E3 group was found to be activated corresponding to the activation of cARC neurons. Our findings suggest that this subpopulation selectively innervate cARC neurons. Accumulating reports have also described c-Fos expression in other TMN subpopulations. Various stress challenge induced c-Fos expression primarily in E4 and E5 subpopulations. Motivation- and drug-induced arousal elicited in common activation of ventrolateral part of the TMN containing E1 and E2 subdivisions, which receive projections from wake-active orexin neurons and sleep-active GABA neurons. These lines of evidence support the hypothesis that there are heterogeneous subpopulations in the TMN that innervated distinct regions to regulate particular functions.     

Neuroplastic changes in the hypothalamic arcuate nucleus: The estradiol effect is accompanied by increased exoendocytotic activity of neuronal membranes

Summary 1. In the rat hypothalamic arcuate nucleus, estradiol induces coordinated changes in the number of axosomatic synapses, the amount of glial ensheathing, and the ultrastructure of the membrane of neuronal somas. In the present study we used conventional electron microscopy and freeze-fracture to examine cellular mechanisms responsible for the estradiol-induced chages at the membrane level.2. In freeze-fracture replicas taken 10–60 min and 24 hr after injection of 17-estradiol to adult ovariectomized females, it was found that there was a rapid increase in the number of exoendocytotic images that reached a plateau by 30 min.3. In thin sections from animals injected 24 hr earlier we demonstrated a significant increase in coated vesicles in the periphery of the neurons and coated pits in the perikaryal membranes and decreased axosomatic synapses.4. We conclude that these morphological alterations are signaling estrogen-induced transport and/or turnover of perikaryal membrane constituents and extracellular components which may affect interneuronal and neuroglial interactions.     

Modulation of molecular mechanisms involved in protein synthesis machinery as a new tool for the control of cell proliferation.

In the past years, the attention of scientists has focused mainly on the study of the genetic information and alterations that regulate eukaryotic cell proliferation and that lead to neoplastic transformation. All therapeutic strategies against cancer are, to date, directed at DNA either with cytotoxic drugs or gene therapy. Little or no interest has been aroused by protein synthesis mechanisms. However, an increasing body of data is emerging about the involvement of translational processes and factors in control of cell proliferation, indicating that protein synthesis can be an additional target for anticancer strategies. In this paper we review the novel insights on the biochemical and molecular events leading to protein biosynthesis and we describe their involvement in cell proliferation and tumorigenesis. A possible mechanistic explanation is given by the interactions that occur between protein synthesis machinery and the proliferative signal transduction pathways and that are therefore suitable targets for indirect modulation of protein synthesis. We briefly describe the molecular tools used to block protein synthesis and the attempts made at increasing their efficacy. Finally, we propose a new multimodal strategy against cancer based on the simultaneous intervention on protein synthesis and signal transduction.     

Homologies of the anterior teeth in Indriidae and a functional basis for dental reduction in primates

In a recent paper Schwartz ('74) proposes revised homologies of the deciduous and permanent teeth in living lemuriform primates of the family Indriidae. However, new evidence provided by the deciduous dentition ofAvahi suggests that the traditional interpretations are correct, specifically: (1) the lateral teeth in the dental scraper of Indriidae are homologous with the incisors of Lemuridae and Lorisidae, not the canines; (2) the dental formula for the lower deciduous teeth of indriids is 2.1.3; (3) the dental formula for the lower permanent teeth of indriids is 2.0.2.3; and (4) decrease in number of incisors during primate evolution was usually in the sequence I3, then I2, then I1. It appears that dental reduction during primate evolution occurred at the ends of integrated incisor and cheek tooth units to minimize disruption of their functional integrity.     

Efficiency of open channel blockers of neuronal nicotinic acetylcholine receptors as estimated from the structure/activity relationship

The participation of definite molecular fragments of bis-cationic ammonium compounds in their blocking effect upon neuronal nicotinic acetylcholine receptors (nAChRs) was deduced from the relationship between the blocking efficacy and three-dimensional molecular models of such compounds that have different fragments. The data on the structure and activity of 15 channel blockers were used for this purpose; predicted blocking effects of the substances were calculated. The correlation coefficients between the blocking activity of the compounds and their predicted efficacy were statistically significant (P > 0.95). The results suggest that HCNCCCCCNCH and HCCNCCCCCNCH fragments (atom chains) with the dimensions of 1.42 and 1.36 nm, respectively, provide the most positive contribution, while a HCNCCCCCNCH fragment with the dimension of 1.36 nm corresponds to highly negative contribution to the blocking activity of compounds. Using the data obtained, we identified the optimum compound structures. The mechanism of the blocking effect upon nAChRs is discussed. Neirofiziologiya/Neurophysiology, Vol. 39, Nos. 4/5, pp. 364–370, July–October, 2007.     

Operant reflex-related neuronal activity in the tectum of the <Emphasis Type="Italic">superior colliculus</Emphasis> and mesencephalic reticular formation of the cat

We tried to answer the question to what extent neurons in the tectum of the superior colliculus (SC) of the cat and in regions of the mesencephalic reticular formation (MRF) localized more ventrally are involved in the control of movements of the limbs. The impulse activity of neurons of the above-mentioned structures was recorded in animals performing targeted operated food-procuring movements by their forelimbs (pressing the pedal). As was found, neurons with impulse reactions correlating with forelimb movements are rather numerous in the SC and adjacent MRF, and there are several groups of neurons, whose impulse responses reached their maxima within different phases of the movements. These were neurons with peaks of the discharge frequency coinciding with the target-reaching movement, with the moment of touching the pedal, with pressing the pedal, and with the development of the muscle force counteracting the forced withdrawal of the limb toward the initial position. Such specific patterns of the responses of different neurons of the SC and neighboring MRF are indicative of a rather specific involvement of the above structures in the control of forelimb movements in cats. Neirofiziologiya/Neurophysiology, Vol. 39, No. 3, pp. 245–254, May–June, 2007.