Catecholaminergic (CA) neurons modulate hypoxic ventilatory response in newborn rats (P7-8)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effect of furosemide treatment on the central and peripheral pressor responses to cholinergic and adrenergic agonists, angiotensin II, hypertonic solution and vasopressin

The present study was performed to investigate the effect of treatment with furosemide on the pressor response induced by intracerebroventricular (i.c.v.) injections of cholinergic (carbachol) and adrenergic (norepinephrine) agonists, angiotensin II (ANGII) and hypertonic saline (HS, 2 M NaCl). The changes induced by furosemide treatment on the pressor response to intravenous (i.v.) norepinephrine, ANGII and arginine vasopressin (AVP) were also studied. Rats with a stainless-steel cannula implanted into the lateral ventricle (LV) were used. Two injections of furosemide (30 mg/kg b.wt. each) were performed 12 and 1 h before the experiments. Treatment with furosemide reduced the pressor response induced by carbachol, norepinephrine and ANGII i.c.v., but no change was observed in the pressor response to i.c.v. 2 M NaCl. The pressor response to i.v. ANGII and norepinephrine, but not AVP, was also reduced after treatment with furosemide. These results show that the treatment with furosemide impairs the pressor responses induced by central or peripheral administration of adrenergic agonist or ANGII, as well as those induced by central cholinergic activation. The results suggest that the treatment with furosemide impairs central and peripheral pressor responses mediated by sympathetic activation and ANGII, but not those produced by AVP. © 1992.

Modulation of synaptic transmission in hippocampal CA1 neurons by a novel neurotoxin (beta-pompilidotoxin) derived from wasp venom

We examined the effects of beta-pompilidotoxin (beta-PMTX), a neurotoxin derived from wasp venom. on synaptic transmission in the mammalian central nervous system (CNS). Using hippocampal slice preparations of rodents, we made both extracellular and intracellular recordings from the CA1 pyramidal neurons in response to stimulation of the Schaffer collateral/commissural fibers. Application of 5-10 muM beta-PMTX enhanced excitatory postsynaptic potentials (EPSPs) but suppressed the fast component of the inhibitory postsynaptic potentials (IPSPs). In the presence of 10 muM bicuculline, beta-PMTX potentiated EPSPs that were composed of both non-NMDA and NMDA receptor-mediated potentials. Potentiation of EPSPs was originated by repetitive firings of the prosynaptic axons, causing Summation of EPSPs. In the presence of 10 muM CNQX and 50 muM APV, beta-PMTX suppressed GABA(A) receptor-mediated fast IPSPs but retained GABA(B) receptor-mediated slow IPSPs. Our results suggest that beta-PMTX facilitates excitatory synaptic transmission by a presynaptic mechanism and that it causes overexcitation followed by block of the activity of some population of interneurons which regulate the activity of GABA(A) receptors. (C) 2001 Published by Elsevier B.V. Ireland Ltd and the Japan Neuroscience Society.

Interaction between the septal area and the subfornical organ in the control of water intake induced by thirst-eliciting procedures

Rats bearing lesions in the septal area followed by lesions in the subfornical organ were submitted to various thirst-eliciting procedures. The rats with hyperdipsia induced by lesions of the septal area drank more water than either during the control period or after lesion of the subfornical organ under the same thirst-eliciting or angiotensin-liberating stimuli (polyethyleneglycol, isoproterenol, water deprivation and ligation of the inferior vena cava). The overdrinking elicited by lesions in the septal area was blocked after lesion of the subfornical organ. Neither hypovolemia, nor hypotension or water deprivation could elicit increased water intake in animals whose subfornical organ had been destroyed. Animals with lesions in the subfornical organ showed decreased water intake after cellular dehydration. The results obtained suggest that the subfornical organ acts as a more important structure than the septal area in the regulation of water intake elicited by angiotensin, with two opposite effects: a direct one facilitating water intake, and an indirect one inhibiting the septal area. The septal area has an inhibitory effect on the subfornical organ and on water intake. © 1980.

Distribution of melanin-concentrating hormone neurons projecting to the medial mammillary nucleus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Orexin in the toad Rhinella schneideri: The location of orexinergic neurons and the role of orexin in ventilatory responses to hypercarbia and hypoxia

Recent reports have suggested that orexins, also known as hypocretins, play an important role in the modulation of respiratory control in mammals, but there are no data available describing the role of the orexinergic system in the peripheral and central chemoreception of non-mammalian vertebrates. Therefore, the present study was designed to examine the localization of orexin-immunoreactive neurons in the brain of toads (Rhinella schneideri) and to investigate the contribution of orexin receptor-1 (OX1R) to the hypoxic and hypercarbic ventilatory responses of these animals during light and dark phases. Our results demonstrated that the orexinergic neurons of R. schneideri are located in the suprachiasmatic nucleus of the diencephalon. Additionally, the intracerebroventricular injection of SB-334867 (OX1R selective antagonist) attenuated the ventilatory response to hypercarbia during the dark phase by acting on tidal volume and breathing frequency, while during the light phase, SB-334867 attenuated the ventilatory response to hypoxia by acting on tidal volume only. We conclude that in the toad R. schneideri, orexinergic neurons are located in the suprachiasmatic nucleus and that OX1R contributes to hypercarbic and hypoxic chemoreflexes.

Activity of neurons in the preoptic area and their participation in reproductive senescence: preliminary findings

Alterations in the hypothalamic-pituitary-gonadal axis in females determine the transition from regular to irregular reproductive cycles, with loss of fertility. Stimulation of noradrenergic neurons of the anteroventral periventricular neurons (AVPV) is essential for regular reproductive cycles. Therefore, we examined the activity of neurons of the AVPV and measure the noradrenaline (NE) of acyclic rats, in constant estrus, and compared it with that of cyclic rats in estrus. Female cyclic (4-5months) and acyclic (17-18months) rats were euthanized at 10, 14, and 18h in estrus. Brains were processed for immunoreactivity to antigens related to Fos (FRA) in AVPV, and the NE was determined by HPLC-ED. Plasma concentrations of LH, FSH, E2 and P4 were determined. In the acyclic animals, plasma LH was higher but the FSH was lower. There was decreasing P4 at different times, while the E2 was constant and lower in acyclic rats. FRA-ir expression in AVPV neurons of acyclic rats as well as turnover of NE was higher when compared with cyclic group. The preliminary findings showed increased activity in AVPV neurons in aging contribute to changes in the temporal pattern of neuroendocrine signaling, compromising the accuracy of inhibitory and stimulatory effects, causing irregularity in the estrous cycle and determining reproductive senescence.

Unpredictable chronic mild stress exerts anxiogenic-like effects and activates neurons in the dorsal and caudal region and in the lateral wings of the dorsal raphe nucleus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Catecholaminergic neurons in the comissural region of the nucleus of the solitary tract modulate hyperosmolality-induced responses

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Estudo comportamental das aferências do núcleo ventral do corpo trapezóide ao primeiro núcleo do circuito neural do reflexo auditivo de sobressalto: núcleo da raiz coclear

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Glial cells modulate the synaptic transmission of NTS neurons sending projections to ventral medulla of Wistar rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Chronic Intermittent Hypoxia Depresses Afferent Neurotransmission in NTS Neurons by a Reduction in the Number of Active Synapses

Long-term synaptic plasticity has been recently described in brainstem areas associated to visceral afferent sensory integration. Chronic intermittent hypoxia (CIH), an animal model for studying obstructive sleep apnea in humans, depresses the afferent neurotransmission in nucleus tractus solitarii (NTS) neurons, which affect respiratory and autonomic regulation. Here we identified the synaptic mechanisms of CIH-induced depression of the afferent neurotransmission in NTS neurons in juvenile rats. We verified that CIH reduced the amplitude of both NMDA and non-NMDA glutamatergic excitatory currents (eEPSCs) evoked by tractus solitarii stimulation (TS-eEPSC) of second-order neurons in the NTS. No changes were observed in release probability, evidenced by absence of any CIH-elicited effects on short-term depression and failures in EPSCs evoked in low calcium. CIH also produced no changes in TS-eEPSC quantal size, since the amplitudes of both low calcium-evoked EPSCs and asynchronous TS-eEPSCs (evoked in the presence of Sr2+) were unchanged. Using single TS afferent fiber stimulation in slices from control and CIH rats we clearly show that CIH reduced the quantal content of the TS-eEPSCs without affecting the quantal size or release probability, suggesting a reduction in the number of active synapses as the mechanism of CIH induced TS-eEPSC depression. In accordance with this concept, the input-output relationship of stimulus intensity and TS-eEPSC amplitude shows an early saturation in CIH animals. These findings open new perspectives for a better understanding of the mechanisms underlying the synaptic plasticity in the brainstem sensory neurons under challenges such as those produced by CIH in experimental and pathological conditions.

Neurotoxicity of Anhydroecgonine Methyl Ester, a Crack Cocaine Pyrolysis Product

Smoking crack cocaine involves the inhalation of cocaine and its pyrolysis product, anhydroecgonine methyl ester (AEME). Although there is evidence that cocaine is neurotoxic, the neurotoxicity of AEME has never been evaluated. AEME seems to have cholinergic agonist properties in the cardiovascular system; however, there are no reports on its effects in the central nervous system. The aim of this study was to investigate the neurotoxicity of AEME and its possible cholinergic effects in rat primary hippocampal cell cultures that were exposed to different concentrations of AEME, cocaine, and a cocaineAEME combination. We also evaluated the involvement of muscarinic cholinergic receptors in the neuronal death induced by these treatments using concomitant incubation of the cells with atropine. Neuronal injury was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and lactate dehydrogenase (LDH) assays. The results of the viability assays showed that AEME is a neurotoxic agent that has greater neurotoxic potential than cocaine after 24 and 48 h of exposure. We also showed that incubation for 48 h with a combination of both compounds in equipotent concentrations had an additive neurotoxic effect. Although both substances decreased cell viability in the MTT assay, only cocaine increased LDH release. Caspase-3 activity was increased after 3 and 6 h of incubation with 1mM cocaine and after 6 h of 0.1 and 1.0mM AEME exposure. Atropine prevented the AEME-induced neurotoxicity, which suggests that muscarinic cholinergic receptors are involved in AEME's effects. In addition, binding experiments confirmed that AEME has an affinity for muscarinic cholinergic receptors. Nevertheless, atropine was not able to prevent the neurotoxicity produced by cocaine and the cocaineAEME combination, suggesting that these treatments activated other neuronal death pathways. Our results suggest a higher risk for neurotoxicity after smoking crack cocaine than after cocaine use alone.

Expression of the P2X(2) receptor in different classes of ileum myenteric neurons in the female obese ob/ob mouse

AIM: To examine whether the ob/ob mouse model of obesity is accompanied by enteric nervous system abnormalities such as altered motility. METHODS: The study examined the distribution of the P2X(2) receptor (P2X(2)R) in myenteric neurons of female ob/ob mice. Specifically, we used immunohistochemistry to analyze the co-expression of the P2X(2)R with neuronal nitric oxide synthase (nNOS), choline acetyltransferase (ChAT), and calretinin (CalR) in neurons of the small intestine myenteric plexus in ob/ob and control female mice. In these sections, we used scanning confocal microscopy to analyze the co-localization of these markers as well as the neuronal density (cm(2)) and area profile (mu m(2)) of P2X(2)R-positive neurons. In addition, enteric neurons were labeled using the nicotinamide adenine dinucleotide (NADH) diaphorase method and analyzed with light microscopy as an alternate means by which to analyze neuronal density and area. RESULTS: In the present study, we observed a 29.6% increase in the body weight of the ob/ob animals (OG) compared to the control group (CG). In addition, the average small intestine area was increased by approximately 29.6% in the OG compared to the CG. Immunoreactivity (IR) for the P2X(2)R, nNOS, ChAT and CaIR was detectable in the myenteric plexus, as well as in the smooth muscle, in both groups. This IR appeared to be mainly cytoplasmic and was also associated with the cell membrane of the myenteric plexus neurons, where it outlined the neuronal cell bodies and their processes. P2X(2)R-IR was observed to co-localize 100% with that for nNOS, ChAT and CaIR in neurons of both groups. In the ob/ob group, however, we observed that the neuronal density (neuron/cm(2)) of P2X(2)R-IR cells was increased by 62% compared to CG, while that of NOS-IR and ChAT-IR neurons was reduced by 49% and 57%, respectively, compared to control mice. The neuronal density of CaIR-IR neurons was not different between the groups. Morphometric studies further demonstrated that the cell body profile area (mu m(2)) of nNOS-IR, ChAT-IR and CaIR-IR neurons was increased by 34%, 20% and 55%, respectively, in the OG compared to controls. Staining for NADH diaphorase activity is widely used to detect alterations in the enteric nervous system; however, our qualitative examination of NADH-diaphorase positive neurons in the nnyenteric ganglia revealed an overall similarity between the two groups. CONCLUSION: We demonstrate increases in P2X(2)R expression and alterations in nNOS, ChAT and CaIR IR in ileal myenteric neurons of female ob/ob mice compared to wild-type controls. (c) 2012 Baishideng. All rights reserved.

Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons

Leao RM, Li S, Doiron B, Tzounopoulos T. Diverse levels of an inwardly rectifying potassium conductance generate heterogeneous neuronal behavior in a population of dorsal cochlear nucleus pyramidal neurons. J Neurophysiol 107: 3008-3019, 2012. First published February 29, 2012; doi:10.1152/jn.00660.2011.-Homeostatic mechanisms maintain homogeneous neuronal behavior among neurons that exhibit substantial variability in the expression levels of their ionic conductances. In contrast, the mechanisms, which generate heterogeneous neuronal behavior across a neuronal population, remain poorly understood. We addressed this problem in the dorsal cochlear nucleus, where principal neurons exist in two qualitatively distinct states: spontaneously active or not spontaneously active. Our studies reveal that distinct activity states are generated by the differential levels of a Ba2+-sensitive, inwardly rectifying potassium conductance (K-ir). Variability in K-ir maximal conductance causes variations in the resting membrane potential (RMP). Low K-ir conductance depolarizes RMP to voltages above the threshold for activating subthreshold-persistent sodium channels (Na-p). Once Na-p channels are activated, the RMP becomes unstable, and spontaneous firing is triggered. Our results provide a biophysical mechanism for generating neural heterogeneity, which may play a role in the encoding of sensory information.