Effects of quisqualate,N-methyl-D-aspartate,and some amino acid antagonists on synaptic transmission in ampullae of Lorenzini

The effects of quisqualic acid (QA), N-methyl-D-aspartate (NMDA), and a number of NMDA and non-NMDA receptor antagonists on background and induced activity in afferent nerve fibers were investigated in skates by means of bath application to the basal membrane of electroreceptors (ampullae of Lorenzini). Perfusion with physiological saline containing QA or NMDA (minimum concentrations required: 10^–8 and 10^–5 M respectively) was found to exert an excitatory effect on afferent activity. Aminoadipate and aminophosphonobutyrate had no effect on synaptic transmission, which was blocked by aminophosphonovalerate, however. Raising magnesium ion concentration (of 30 mM) led to blockade of NMDA-induced response without changing that produced by QA. Aminophosphonovalerate blocked NMDA response and partially reduced the effects of L-aspartic acid. Glutamyl glycine produced blockade of synaptic transmission. The findings obtained would point to synaptic sensitivity to the action of amino acid agonists (QA and NMDA) in the ampullae of Lorenzini.Neurocybernetics Research Institute, Rostov-on-Don. Translated from Neirofiziologiya, Vol. 21, No. 2, pp. 160–167, March–April, 1989.     

The Excitotoxin Quinolinic Acid Induces Tau Phosphorylation in Human Neurons

Some of the tryptophan catabolites produced through the kynurenine pathway (KP), and more particularly the excitotoxin quinolinic acid (QA), are likely to play a role in the pathogenesis of Alzheimer''s disease (AD). We have previously shown that the KP is over activated in AD brain and that QA accumulates in amyloid plaques and within dystrophic neurons. We hypothesized that QA in pathophysiological concentrations affects tau phosphorylation. Using immunohistochemistry, we found that QA is co-localized with hyperphosphorylated tau (HPT) within cortical neurons in AD brain. We then investigated in vitro the effects of QA at various pathophysiological concentrations on tau phosphorylation in primary cultures of human neurons. Using western blot, we found that QA treatment increased the phosphorylation of tau at serine 199/202, threonine 231 and serine 396/404 in a dose dependent manner. Increased accumulation of phosphorylated tau was also confirmed by immunocytochemistry. This increase in tau phosphorylation was paralleled by a substantial decrease in the total protein phosphatase activity. A substantial decrease in PP2A expression and modest decrease in PP1 expression were observed in neuronal cultures treated with QA. These data clearly demonstrate that QA can induce tau phosphorylation at residues present in the PHF in the AD brain. To induce tau phosphorylation, QA appears to act through NMDA receptor activation similar to other agonists, glutamate and NMDA. The QA effect was abrogated by the NMDA receptor antagonist memantine. Using PCR arrays, we found that QA significantly induces 10 genes in human neurons all known to be associated with AD pathology. Of these 10 genes, 6 belong to pathways involved in tau phosphorylation and 4 of them in neuroprotection. Altogether these results indicate a likely role of QA in the AD pathology through promotion of tau phosphorylation. Understanding the mechanism of the neurotoxic effects of QA is essential in developing novel therapeutic strategies for AD.     

Possible role of cGMP in excitatory amino acid induced cytotoxicity in cultured cerebral cortical neurons

Using cultured cerebral cortical neurons at mature stages (9 days in culture, d.i.c.) it was demonstrated that glutamate, NMDA (N-methyl-D-aspartate) and to a lesser extent KA (kainate) increase the intracellular cGMP concentration ([cGMP]_i) whereas no such effect was observed after exposure of the cells of QA (quisqualate) and AMPA (2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propionate). No effect of glutamate, NMDA and KA was observed in immature neurons (2 d.i.c.). The pharmacology of these cGMP responses was investigated using the glutamate antagonists APV (2-amino-5-phosphonovalerate) with selectivity for NMDA receptors, CNQX (6-cyano-7-nitro-quinoxaline-2,3-dione) with selectivity for non-NMDA receptors and the novel KA selective antagonists AMOA (2-amino-3-[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propionate) and AMNH (2-amino-3-[2-(3-hydroxy-5-methylisoxazol-4-yl)methyl-5-methyl-3-oxoisoxazolin-4-yl]propionate). In addition, the cytotoxicity of glutamate, NMDA and KA was studied and found to be enhanced by addition of the non-metabolizable cGMP analogue 8-Br-cGMP. On the contrary, the toxicity of QA and AMPA was not affected by 8-Br-cGMP. Pertussis toxin augmented the toxicity elicited by glutamate, NMDA, KA and QA but not that induced by AMPA. On the other hand, only glutamate and KA induced toxicity was potentiated by cholera toxin, which also enhanced the stimulatory effect of glutamate and NMDA but not that of KA on the cellular cGMP content. The toxicity as well as the effects on intracellular cGMP levels could be antagonized by the specific excitatory amino acid (EAA) antagonists. These results suggest that the mechanisms by which the various excitatory amino acids exert cytotoxicity are different, and that increased cGMP levels may participate in the mediation of glutamate, NMDA or KA induced toxicity but less likely in QA and AMPA mediated toxicity. Furthermore, G-proteins or other pertussis or cholera toxin sensitive entities seem to be involved in the cytotoxic action of all excitatory amino acids except AMPA.     

Role of Endogenous Taurine on the Glutamate Analogue-Induced Neurotoxicity in the Rat Hippocampus In Vivo

The glutamate analogues N-methyl-D-aspartate (NMDA), kainic acid (KA), and quisqualic acid (QA), prepared in different hypertonic media, were perfused in vivo in the hippocampal CA1 field of rats using a microdialysis technique. Extracellular taurine levels, estimated after analysis of the taurine content of dialysates, increased during perfusion of all three agonists but varied according to the osmolarity of the medium. The NMDA-induced increase in extracellular taurine content was only slightly inhibited by perfusion of 150 and 300 mM sucrose. The KA-evoked increase was partially dependent on extracellular osmolarity, because addition of 50 and 150 mM sucrose caused a dose-dependent inhibition that was not augmented using higher sucrose concentrations. QA caused a taurine increase that was totally abolished by addition of 50 mM sucrose. These results indicate that the rise in extracellular taurine level elicited by QA and part of the increase elicited by KA are probably due to a release caused by the cellular swelling that these substances evoke, a finding substantiating the previously proposed osmoregulatory role of taurine. However, almost all the increase in extracellular taurine content caused by NMDA and all the osmotically insensitive part of the KA-evoked rise cannot be explained as release triggered by cell swelling and may reflect a function of taurine other than osmoregulation.     

Pharmacological and functional characterization of excitatory amino acid mediated cytotoxicity in cerebral cortical neurons

The cytotoxic action of the excitatory amino acids (EAAs) glutamate, N-methyl- D-aspartate (NMDA), quisqualate (QA), kainate (KA) and (RS)-2-amino-3(3-hydoxy-5-methylisoxazol-4-yl) propionate (AMPA) was studied in cerebral cortical neurons in culture. The pharmacological profile of these actions was characterized using the NMDA selective antagonist D-(-)-2-amino-5- phosphonopentanoate (APV) and the non-NMDA selective antagonists 6.7- dinitroquinoxaline-2,3-dione (DNQX), 2-amino-3[3-(carboxymethoxy)-5- methylisoxazol-4-yl]-propionate (AMOA) and 2-amino-3-[2-(3-hydroxy-5- methylisoxazol-4-yl)methyl-3-methyl-3-oxoisoxazolin-4-yl] propionate (AMNH). The role of intracellular Ca⁺⁺ homeostasis and cGMP production for development of EAA mediated cytotoxicity was assessed by measurements of changes in [Ca⁺⁺]i using the flourescent Ca⁺⁺ chelator Fluo-3 and in cGMP concentrations using a conventional radioimmune assay. It was found that glutamate toxicity involves both NMDA and non-NMDA receptor activation and that aberrations in Ca⁺⁺ homeostasis brought about by Ca⁺⁺ influx and/or liberation of Ca⁺⁺ from internal stores aare important for development of toxicity. The drug dantrolene which prevents release of Ca⁺⁺ from such stores can prevent toxicity induced by glutamate, NMDA and QA completely but has no effect on KA and AMPA toxicity. Changes in cGMP levels appear to play a role for development of glutamate, NMDA and KA toxicity but does not seem to be involved in that triggered by QA and AMPA.Abbreviations AMNH: (2-amino-3-[2-(3-hydroxy-5-methylisoxazol-4-yl)methyl-5-methyl-3-oxoisoxazolin-4-yl]propionate) - AMOA: (2-amino-3[3-(carboxymethoxy)-5-methylisoxazol-4-yl]propinate) - AMPA: ( (RS) —2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl)propinate) - APV: (D-(-)-2-amino-5-phosphonopentanoate) - DNQX: (6,7-dinitroquinoxaline-2,3-dione) - KA (kinate) - QA (quisqualate)     

Action of precursors of noradrenaline synthesis on membrane receptors of chick embryo spinal neurons

Effects of noradrenaline precursors on glycine and N-methyl-D-aspartate (NMDA) receptors in spinal cord neurons recently isolated from chick embryo were investigated using whole cell patch-clamp and concentration clamp techniques. Both L-alanine and L-DOPA were found to be glycine agonists capable of potentiating NMDA response, while L-tyrosine does not activate glycine but can potentiate NMDA response. Lastly, L-phenylalanine and dopamine do not interact with either glycine or NMDA receptors.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 5, pp. 665–670, September–October, 1990.     

<Emphasis Type="Italic">N</Emphasis>-methyl-<Emphasis Type="SmallCaps">D</Emphasis>-aspartate Receptors are Involved in the Quinolinic Acid,but not in the Malonate Pro-oxidative Activity <Emphasis Type="Italic">in vitro</Emphasis>

Oxidative stress plays a significant role in the neurotoxicity of a variety of agents that interact with the N-methyl-D-aspartate (NMDA) receptors. Here we investigated in a comparative way the pro-oxidative effects of quinolinic acid (QA) and malonate, two neurotoxic substances that act through distinct primary molecular mechanisms on the production of thiobarbituric acid reactive species (TBARS) by brain homogenates. In fact, QA is thought to activate directly the NMDA receptor, whereas malonate seems to act primarily by inhibiting oxidative metabolism. The malonate-induced TBARS formation was not modified by cyanide (CN^–) or 2,4-dinitrophenol. MK-801 did not reduce basal or malonate induced-TBARS production in fresh tissues preparations. However, in heat-treated preparations a significant effect of MK-801 against basal TBARS production was observed, but not on the malonate induced-TBARS production. QA induced-TBARS production was significantly prevented by MK-801 either in fresh or heat-treated preparations. The antioxidant effect of MK-801 on basal and QA-induced TBARS production increased as the temperatures used to treat S1 were increased. Succinate dehydrogenase (SDH) was inhibited by malonate but not by QA. Malonate was able to chelate iron(II) and the malonate-iron complex(es) is(are) active as measured by its(their) activity on deoxyribose degradation assay. These findings indicate that direct interactions of malonate with NMDA receptors are not involved in malonate pro-oxidative activity in vitro. QA pro-oxidative activity in vitro was related, at least in part, to its capability in stimulate NMDA receptors. Taken together, these findings indicated that malonate pro-oxidative activity in vitro could be attributed to its capability of changing the ratio Fe²⁺/ Fe³⁺, which is essential to TBARS production.     

ATP Induces NO Production in Hippocampal Neurons by P2X7 Receptor Activation Independent of Glutamate Signaling

To assess the putative role of adenosine triphosphate (ATP) upon nitric oxide (NO) production in the hippocampus, we used as a model both rat hippocampal slices and isolated hippocampal neurons in culture, lacking glial cells. In hippocampal slices, additions of exogenous ATP or 2′(3′)-O-(4-Benzoylbenzoyl) ATP (Bz-ATP) elicited concentration-dependent NO production, which increased linearly within the first 15 min and plateaued thereafter; agonist EC₅₀ values were 50 and 15 µM, respectively. The NO increase evoked by ATP was antagonized in a concentration-dependent manner by Coomassie brilliant blue G (BBG) or by N^ω-propyl-L-arginine, suggesting the involvement of P2X₇Rs and neuronal NOS, respectively. The ATP induced NO production was independent of N-methyl-D-aspartic acid (NMDA) receptor activity as effects were not alleviated by DL-2-Amino-5-phosphonopentanoic acid (APV), but antagonized by BBG. In sum, exogenous ATP elicited NO production in hippocampal neurons independently of NMDA receptor activity.     

Acute tolerance to ethanol inhibition of NMDA-induced responses in rat rostral ventrolateral medulla neurons

The present study was performed to examine the effects of acute ethanol exposure on N-methyl-D-aspartate (NMDA)-induced responses and the development of acute tolerance in rat rostral ventrolateral medulla (RVLM) in vivo and in vitro. Repeated microinjections of NMDA (0.14 nmol) into the RVLM every 30 min caused reproducible increases in mean arterial pressure in urethane-anesthetized rats weighing 325–350 g. Intravenous injections of ethanol (0.16 or 0.32 g, 1 ml) inhibited NMDA-induced pressor effects in a blood-concentration-dependent and reversible manner. The inhibitory effect of ethanol was reduced over time during continuous infusion of ethanol or on the second injection 3.5 h after prior injection of a higher dose of ethanol (0.32 g). A high dose of ethanol (0.32 g) had no significant effects on-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid,-aminobutyric acid and glycine-induced changes in blood pressure. In vitro studies showed that ethanol (10–100 mM) dose-dependently inhibited inward currents elicited by pressure ejection of NMDA (10 mM) in RVLM neurons of neonatal brainstem slice preparations. When the superfusion time of ethanol (100 mM) was increased to 50 min, its inhibitory effect decreased gradually after 30–40 min in 60% of RVLM neurons examined. These data suggested that ethanol inhibition and subsequent tolerance development is associated with changed sensitivity to NMDA in the RVLM, which may play important roles in the ethanol regulation of cardiovascular function.     

Quinolinic acid stimulates synaptosomal glutamate release and inhibits glutamate uptake into astrocytes

Quinolinic acid (QA) is an endogenous neurotoxin involved in various neurological diseases, whose action seems to be exerted via glutamatergic receptors. However, the exact mechanism responsible for the neurotoxicity of QA is far from being understood. We have previously reported that QA inhibits vesicular glutamate uptake. In this work, investigating the effects of QA on the glutamatergic system from rat brain, we have demonstrated that QA (from 0.1 to 10mM) had no effect on synaptosomal L-[3H]glutamate uptake. The effect of QA on glutamate release in basal (physiological K+ concentration) or depolarized (40 mM KCl) conditions was evaluated. QA did not alter K+-stimulated glutamate release, but 5 and 10mM QA significantly increased basal glutamate release. The effect of dizolcipine (MK-801), a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) receptor on glutamate release was investigated. MK-801 (5 microM) did not alter glutamate release per se, but completely abolished the QA-induced glutamate release. NMDA (50 microM) also stimulated glutamate release, without altering QA-induced glutamate release, suggesting that QA effects were exerted via NMDA receptors. QA (5 and 10mM) decreased glutamate uptake into astrocyte cell cultures. Enhanced synaptosomal glutamate release, associated with inhibition of glutamate uptake into astrocytes induced by QA could contribute to increase extracellular glutamate concentrations which ultimately lead to overstimulation of the glutamatergic system. These data provide additional evidence that neurotoxicity of QA may be also related to disturbances on the glutamatergic transport system, which could result in the neurological manifestations observed when this organic acid accumulates in the brain.     

Excitotoxin-induced changes in transglutaminase during differentiation of cerebellar granule cells

Summary. Excitotoxicity induced by NMDA receptor stimulation is able to increase the activity of many enzymes involved in neuronal cell death. Primary cultures of rat cerebellar granule cells were used to elucidate the role of transglutaminase reaction in the excitotoxic cell response, and to evaluate the role of glutamate receptors in cell survival and degeneration. Granule neurons, maintained in vitro for two weeks, were exposed to NMDA at different stages of differentiation. Following NMDA receptor activation, increases in transglutaminase activity were observed in cell cultures. The levels of enzyme activity were higher in cells at 5 days in vitro than in those at 8–9 or 13–14 days in vitro. Moreover, NMDA exposure up-regulated tTG expression in neurons as young as 5 days in vitro. These cultures also exhibited morphological changes with clear apoptotic features. Results obtained demonstrate that susceptibility of granule cells to excitotoxicity depends on the developmental stage of neurons.     

Enhanced NMDA Receptor-Mediated Modulation of Excitatory Neurotransmission in the Dorsal Vagal Complex of Streptozotocin-Treated,Chronically Hyperglycemic Mice

A variety of metabolic disorders, including complications experienced by diabetic patients, have been linked to altered neural activity in the dorsal vagal complex. This study tested the hypothesis that augmentation of N-Methyl-D-Aspartate (NMDA) receptor-mediated responses in the vagal complex contributes to increased glutamate release in the dorsal motor nucleus of the vagus nerve (DMV) in mice with streptozotocin-induced chronic hyperglycemia (i.e., hyperglycemic mice), a model of type 1 diabetes. Antagonism of NMDA receptors with AP-5 (100 μM) suppressed sEPSC frequency in vagal motor neurons recorded in vitro, confirming that constitutively active NMDA receptors regulate glutamate release in the DMV. There was a greater relative effect of NMDA receptor antagonism in hyperglycemic mice, suggesting that augmented NMDA effects occur in neurons presynaptic to the DMV. Effects of NMDA receptor blockade on mEPSC frequency were equivalent in control and diabetic mice, suggesting that differential effects on glutamate release were due to altered NMDA function in the soma-dendritic membrane of intact afferent neurons. Application of NMDA (300 μM) resulted in greater inward current and current density in NTS neurons recorded from hyperglycemic than control mice, particularly in glutamatergic NTS neurons identified by single-cell RT-PCR for VGLUT2. Overall expression of NR1 protein and message in the dorsal vagal complex were not different between the two groups. Enhanced postsynaptic NMDA responsiveness of glutamatergic NTS neurons is consistent with tonically-increased glutamate release in the DMV in mice with chronic hyperglycemia. Functional augmentation of NMDA-mediated responses may serve as a physiological counter-regulatory mechanism to control pathological disturbances of homeostatic autonomic function in type 1 diabetes.     

大鼠新鲜分离DRG神经元胞体膜谷氨酸受体亚型及其分布

本文目的是研究ＤＲＧ神经元膜谷氨酸受体亚型的分布及其共存情况。实验在ＤＲＧ分离细胞上应用膜片带技术记录ＮＭＤＡ－,ＫＡ－和ＱＡ／ＡＭＰＡ－激活电流。在受检的３７个细胞中７０．３％的细胞对ＮＭＤＡ敏感;１８．９％的细胞对ＫＡ敏感;５６．８％的细胞对ＱＡ敏感。其分布的情况是：单独存在一种受体的细胞为１５个;二种受体共存的细胞为１３个;三种受体共存的细胞为４个．另外有４个细胞三种受体均无。     

Excitatory amino acid receptor-channels in Purkinje cells in thin cerebellar slices.

Glutamate receptors of the N-methyl-D-aspartate (NMDA) and non-NMDA type serve different functions during excitatory synaptic transmission. Although many central neurons bear both types of receptor, the evidence concerning the sensitivity of cerebellar Purkinje cells to NMDA is contradictory. To investigate the receptor types present in Purkinje cells, we have used whole-cell and outside-out patch-clamp methods to record from cells in thin cerebellar slices from young rats. At a holding potential of -70 mV (in nominally Mg(2+)-free medium, with added glycine) NMDA caused a whole-cell current response which consisted of a dramatic increase in the frequency of synaptic currents. In the presence of tetrodotoxin (TTX) and the gamma-aminobutyric acidA (GABAA) receptor antagonist bicuculline, spontaneous synaptic currents and responses to NMDA were inhibited. In a proportion of cells a small polysynaptic response to NMDA persisted, which was further reduced by the non-NMDA receptor antagonist 6-cyano-2,3-dihydro-7-nitroquinoxalinedione (CNQX). The non-NMDA glutamate receptor agonists kainate (KA), quisqualate (QA) and s-alpha-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (s-AMPA), evoked large inward currents due to the direct activation of receptors in Purkinje cells. NMDA applied to excised membrane patches failed to evoke any single-channel currents, whereas s-AMPA and QA caused small inward currents accompanied by marked increases in current noise. Spectral analysis of the s-AMPA noise in patches gave an estimated mean channel conductance of approximately 4 pS.(ABSTRACT TRUNCATED AT 250 WORDS)     

Excitatory amino acids as modulators of gonadotropin secretion

Summary The effects of quinolinic acid (QUIN) and quisqualate (QA) on the secretion of GnRH from MBH and LH and FSH from AP of 50 day old male rats have been evaluated by means of an in vitro perifusion technique.QUIN (100µM) is able to increase GnRH secretion with an action mediated by an NMDA receptor type, as shown by the inhibitory effect exerted by both a competitive (AP-5) and a non-competitive (MK-801) specific antagonist.QA per se at the concentrations tested (1–100µM) does not modify GnRH and gonadotropin secretion, but in the presence of a specific KA/QA receptor antagonist (DNQX) exerts a stimulatory effect at both levels.This observation might indicate that of the two QA receptor subtypes (ionotropic and metabotropic), this agonist binds to the metabotropic one with very low affinity: thus it is likely that a higher dose is required in order to have any effect on gonadotropin secretion. However, in the presence of DNQX, which binds to the ionotropic receptor, all the available QA can bind to the metabotropic one and can exert its action at MBH AP levels.     

Intracerebroventricular Guanine-Based Purines Protect Against Seizures Induced by Quinolinic Acid in Mice

Acute and chronic administration of the nucleoside guanosine have been shown to prevent quinolinic acid (QA) and -dendrotoxin-induced seizures, as well as to impair memory and anxiety in rats and mice. In this study, we investigated the effect of i.c.v. administration of guanine-based purines (GTP, GDP, GMP, and guanosine) against seizures induced by the NMDA agonist and glutamate releaser quinolinic acid in mice. We also aimed to study the effects of the poorly hydrolysable analogs of GTP (GppNHp and GTPS) and GDP (GDPS) in this seizure model. QA produced seizures in 100% of mice, an effect partially prevented by guanine-based purines. In contrast to GTP (480 nmol), GDP (320–640 nmol), GMP (320–480 nmol) and guanosine (300–400 nmol), the poorly hydrolysable analogs of GTP and GDP did not affect QA-induced seizures. Thus, the protective effects of guanine nucleotides seem to be due to their conversion to guanosine. Altogether, these findings suggest a potential role of guanine-based purines for treating diseases involving glutamatergic excitotoxicity.     

Spectroscopic characterization of quinone-site mutants of the bacterial photosynthetic reaction center

Site-specific mutations in the quinone binding sites of the photosynthetic reaction center (RC) protein complexes of Rhodobacter (R.) capsulatus caused pronounced effects on sequential electron transfer. Conserved residues that break the twofold symmetry in this region of the RC – M246Ala and M247Ala in the QA binding pocket, and L212Glu and L213Asp in the QB binding pocket – were targeted. We constructed a QB-site mutant, L212Glu-L213Asp Ala-Ala, and a QA-site mutant, M246Ala–M247Ala Glu-Asp, to partially balance the differences in charge distribution normally found between the two quinone binding sites. In addition, two photocompetent revertants were isolated from the photosynthetically-incompetent M246Glu-M247Asp mutant: M246Ala–M247Asp and M246Gly–M247Asp. Sequential electron transfer was investigated by continuous light excitation and time-resolved electron paramagnetic resonance (EPR), and time-resolved optical techniques. Several lines of EPR evidence suggested that the forward electron transfer rate to QA, kQ, was slowed in those strains containing altered QA sites. The slower rates of secondary electron transfer were confirmed by time-resolved optical results with the M246Glu-M247Asp mutations in the QA site resulting in a dramatically lowered secondary electron transfer efficiency [kQ < (2 ns)-1] in comparison with either the native R. capsulatus RC or the QB site mutant [kQ (200 ps)-1]. Secondary electron transfer in the two revertants was intermediate between that of the native RC and the QA mutant. The P+ QA- PQA charge recombination rates were also changed in the strains that carried altered QA sites. We show that local mutations in the QA site, presumably through local electrostatic changes, significantly alter binding and electron transfer properties of QA.     

Changes in the background activity of neurons of the central gray substance when serotonin is applied to it or its synthesis is blocked

The changes in the background activity (BA) of neurons of the central gray substance upon the iontophoretic application of serotonin (ST) to them in a concentration of 1·10^–4 mole/liter, and following the blockage of its synthesis by pchlorophenylalanine (PCPA), were investigated in hexenal-anesthetized rats. The application of ST led to changes in the BA only in group III neurons, in which the BA was distinguished by continuous action potential generation. The application of ST elicited an increase in the frequency of the BA in 21.2% of such neurons, suppression in 45.5%, and the BA remained unchanged in 33.3% of the units. The identified changes in the BA in these neurons coincided with those which arose as the result of stimulation of the monoaminergic structures. When the application of ST was combined with stimulation of the locus coeruleus (LC), the substantia nigra (SN), and the nucleus raphe magnus (NRM), the suppression of the BA was intensified; however, when the LS and the SN were stimulated, the suppression was more pronounced than with stimulation of the NRM. The intensity of the suppressant effect of the NRM decreased after preliminary administration of PCPA, but it did not disappear completely, and the influences elicited by the LS and the SN intensified. The mechanisms of the serotoninergic control of the activity of the neurons of the central gray substance are discussed.A. A. Bogomolets Institute of Physiology, Ukrainian Academy of Sciences, Kiev. Translated from Neirofiziologiya, Vo. 24, No. 2, pp. 169–177, March–April, 1992.     

Responses of motor neurons of lumbar section of spinal cord elicited by the activity of the propriospinal pathways

We have carried out intracellular recording from the motor neurons of the lumbar section of the cat spinal cord with electrical stimulation of the propriospinal axons descending in the dorsolateral funiculus. To prevent activation of the long descending pathways of the lateral funiculus, ipsilateral hemisectioning of the spine was performed in the segments L₁-L₂ 10–14 days before the experiment. Stimulation of the dorsolateral funiculus in two segments cranial to the point of recording elicited in the flexor motor neurons essentially e.p.s.p. and in the extensor neurons i.p.s.p. with a latent period, on the average, of 1.97 and 1.93 msec, respectively. The amplitude of such p.s.p. considerably rose with rise in the frequency of stimulation of the funiculus to 50–100 a second. Activation of the segmental interneurons was observed only in a few cases. It is assumed that the synaptic processes elicited in the lumbar motor neurons are the result of the monosynaptic influences of the propriospinal neurons.A. A. Bogomolets' Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 1, No. 1, pp. 5–14, July–August, 1969.