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Excitatory Synaptic Transmission (excitatory + synaptic_transmission)
Selected AbstractsCooling Abolishes Neuronal Network Synchronization in Rat Hippocampal SlicesEPILEPSIA, Issue 6 2002Sam P. Javedan Summary: ,Purpose: We sought to determine whether cooling brain tissue from 34 to 21°C could abolish tetany-induced neuronal network synchronization (gamma oscillations) without blocking normal synaptic transmission. Methods: Intracellular and extracellular electrodes recorded activity in transverse hippocampal slices (450,500 ,m) from Sprague,Dawley male rats, maintained in an air,fluid interface chamber. Gamma oscillations were evoked by afferent stimulation at 100 Hz for 200 ms. Baseline temperature in the recording chamber was 34°C, reduced to 21°C within 20 min. Results: Suprathreshold tetanic stimuli evoked membrane potential oscillations in the 40-Hz frequency range (n = 21). Gamma oscillations induced by tetanic stimulation were blocked by bicuculline, a ,-aminobutyric acid (GABA)A -receptor antagonist. Cooling from 34 to 21°C reversibly abolished gamma oscillations in all slices tested. Short, low-frequency discharges persisted after cooling in six of 14 slices. Single-pulse,evoked potentials, however, were preserved after cooling in all cases. Latency between stimulus and onset of gamma oscillation was increased with cooling. Frequency of oscillation was correlated with chamber cooling temperature (r = 0.77). Tetanic stimulation at high intensity elicited not only gamma oscillation, but also epileptiform bursts. Cooling dramatically attenuated gamma oscillation and abolished epileptiform bursts in a reversible manner. Conclusions: Tetany-induced neuronal network synchronization by GABAA -sensitive gamma oscillations is abolished reversibly by cooling to temperatures that do not block excitatory synaptic transmission. Cooling also suppresses transition from gamma oscillation to ictal bursting at higher stimulus intensities. These findings suggest that cooling may disrupt network synchrony necessary for epileptiform activity. [source] Orexin B/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2008S. L. Borgland Abstract The orexins (hypocretins) play a crucial role in arousal, feeding and reward. Highly relevant to these functions, orexin-containing neurons from the lateral hypothalamus project densely to the ventral tegmental area (VTA), which is the origin of dopamine projections implicated in motivation and reward. Orexin A/hypocretin 1 (oxA/hcrt-1) can enable long-term changes associated with drugs of abuse; however, the effects of orexin B/hypocretin 2 (oxB/hcrt-2) on excitatory synaptic transmission in the VTA are unknown. We used whole-cell patch-clamp electrophysiology in rat horizontal midbrain slices to examine the effects of oxB/hcrt-2 on excitatory synaptic transmission. We observed that oxB/hcrt-2 has distinct effects from oxA/hcrt-1 in the VTA. oxB/Hcrt-2 (100 nm) increased presynaptic glutamate release in addition to a postsynaptic potentiation of NMDA receptors (NMDARs). The oxB/hcrt-2-mediated postsynaptic potentiation of NMDARs was mediated via activation of orexin/hypocretin 2 (OX2/Hcrt-2) receptors and protein kinase C (PKC). Furthermore, the increase in transmitter release probability was also PKC-dependent, but not through activation of orexin/hypocretin 1 (OX1/Hcrt-1) or OX2/Hcrt-2 receptors. Finally, oxB/hcrt-2 or the selective OX2/Hcrt-2 receptor agonist ala11 - d -leu15 -orexin B, significantly reduced spike-timing-induced long-term potentiation. Taken together, these results support a dual role for oxB/hcrt-2 in mediating enhanced glutamatergic transmission in the VTA, and suggest that oxA/hcrt-1 and oxB/hcrt-2 exert different functional roles in modulating the enhancement of the motivational components of arousal and feeding. [source] In vivo optical recordings of synaptic transmission and intracellular Ca2+ and Cl, in the superior colliculus of fetal ratsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2006Yoshiyuki Sakata Abstract Although the N -methyl- d -aspartate (NMDA) receptor is known to play a crucial role in activity-dependent remodeling of synaptic connections in the fetal superior colliculus (SC), its contribution to the electrical activity of fetal SC neurons has not been determined. Furthermore, whether ,-aminobutyric acid (GABA)-mediated inhibition occurs either as early as prenatal periods or only after eye opening has been controversial. We therefore performed optical recordings using voltage-, Ca2+ - and Cl, -sensitive fluorescent dyes to analyse synaptic transmission and changes in intracellular Ca2+ and Cl, in the SC of fetal rats that were still connected with the dams by the umbilical cord. Excitatory and inhibitory responses were evoked by focal SC stimulation. The excitatory synaptic responses are composed of early and late components. The early component was mediated by both non-NMDA and NMDA receptors, whereas the late component occurred mainly via NMDA receptors. Train pulse stimulation at higher currents was required for induction of the inhibition, which was antagonized by bicuculline, and blocking of the GABA-mediated inhibition by bicuculline uncovered masked excitatory synaptic responses. Focal SC stimulation induced increases in [Cl,]i and [Ca2+]i that were mediated by GABA-A receptors and mainly by NMDA receptors, respectively. GABA antagonists augmented SC-induced increases in [Ca2+]i. These results indicate that, in the fetal SC, excitatory and inhibitory synaptic transmissions occur before birth, that the NMDA receptor is a major contributor to excitatory synaptic transmission and increased [Ca2+]i, and that the GABA-A receptor is already functioning to inhibit excitatory neurotransmission. [source] Depression of retinogeniculate synaptic transmission by presynaptic D2 -like dopamine receptors in rat lateral geniculate nucleusEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 2 2006G. Govindaiah Abstract Extraretinal projections onto neurons in the dorsal lateral geniculate nucleus (dLGN) play an important role in modifying sensory information as it is relayed from the visual thalamus to neocortex. The dLGN receives dopaminergic innervation from the ventral tegmental area; however, the role of dopamine in synaptic transmission in dLGN has not been explored. In the present study, whole cell recordings were obtained to examine the actions of dopamine on glutamatergic synaptic transmission. Dopamine (2,100 µm) strongly suppressed excitatory synaptic transmission in dLGN relay neurons that was evoked by optic tract stimulation and mediated by both N -methyl- d -aspartate and non -N -methyl- d -aspartate glutamate receptors. In contrast, dopamine did not alter inhibitory synaptic transmission arising from either dLGN interneurons or thalamic reticular nucleus neurons. The suppressive action of dopamine on excitatory synaptic transmission was mimicked by the D2 -like dopamine receptor agonist bromocriptine (2,25 µm) but not by the D1 -like receptor agonist SKF38393 (10,25 µm). In addition, the dopamine-mediated suppression was antagonized by the D2 -like receptor antagonist sulpiride (10,20 µm) but not by the D1 -like receptor antagonist SCH23390 (5,25 µm). The dopamine-mediated decrease in evoked excitatory postsynaptic current amplitude was accompanied by an increase in the magnitude of paired-pulse depression. Furthermore, dopamine also reduced the frequency but not the amplitude of miniature excitatory postsynaptic currents. Taken together, these data suggest that dopamine may act presynaptically to regulate the release of glutamate at the retinogeniculate synapse and modify transmission of visual information in the dLGN. [source] AMPA/kainate and NMDA-like glutamate receptors at the chromatophore neuromuscular junction of the squid: role in synaptic transmission and skin patterningEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003Pedro A. Lima Abstract Glutamate receptor types were examined at the chromatophore synapses of the squids Alloteuthis subulata and Loligo vulgaris, where nerve-induced muscle contraction causes chromatophore expansion. Immunoblotting with antibody raised against a squid AMPA receptor (sGluR) demonstrated that AMPA/kainate receptors are present in squid skin. Application of l -glutamate evoked chromatophore muscle contractions in both ventral and dorsal skins, while NMDA was only active on a subpopulation of dorsal chromatophores. In dorsal skin, neurotransmission was partly blocked by either AMPA/kainate receptor antagonists (CNQX and DNQX) or NMDA receptor antagonists (AP-5 and MK-801) or completely blocked by simultaneous application of both classes of antagonists. In isolated muscle fibres, ionophoretic application of l -glutamate evoked fast inward CNQX- and DNQX-sensitive currents with reversal potentials around +14 mV and a high conductance to Na+. In fibres from dorsal skin only, a slower outward glutamate-sensitive current appeared at positive holding potentials. At negative potentials, currents were potentiated by glycine or by removing external Mg2+ and were blocked by AP-5 and MK-801. Glutamate caused a fast, followed by a slow, transient increase in cytoplasmic Ca2+. The slow component was increased in amplitude and duration by glycine or by lowering external Mg2+ and decreased by AP-5 and MK-801. In cells from ventral skin, no ,NMDA-like responses' were detected. Thus, while AMPA/kainate receptors mediated fast excitatory synaptic transmission and rapid colour change over the whole skin, activation of both AMPA/kainate and NMDA-like receptors in a subpopulation of dorsal chromatophores prolonged the postsynaptically evoked Ca2+ elevation causing temporally extended colour displays with behavioural significance. [source] Presynaptic inhibition of Schaffer collateral synapses by stimulation of hippocampal cholinergic afferent fibresEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2003David Fernández de Sevilla Abstract It has been known for decades that muscarinic agonists presynaptically inhibit Schaffer collateral synapses contacting hippocampal CA1 pyramidal neurons. However, a demonstration of the inhibition of Schaffer collateral synapses induced by acetylcholine released by cholinergic hippocampal afferents is lacking. We present original results showing that electrical stimulation at the stratum oriens/alveus with brief stimulus trains inhibited excitatory postsynaptic currents evoked by stimulation of Schaffer collaterals in CA1 pyramidal neurons of rat hippocampal slices. The increased paired-pulse facilitation and the changes in the variance of excitatory postsynaptic current amplitude that paralleled the inhibition suggest that it was mediated presynaptically. The effects of oriens/alveus stimulation were inhibited by atropine, and blocking nicotinic receptors with methyllycaconitine was ineffective, suggesting that the inhibition was mediated via the activation of presynaptic muscarinic receptors. The results provide a novel demonstration of the presynaptic inhibition of glutamatergic neurotransmission by cholinergic fibres in the hippocampus, implying that afferent cholinergic fibres regulate the strength of excitatory synaptic transmission. [source] Large-scale expression and thermodynamic characterization of a glutamate receptor agonist-binding domainFEBS JOURNAL, Issue 13 2000Dean R. Madden The ionotropic glutamate receptors (GluR) are the primary mediators of excitatory synaptic transmission in the brain. GluR agonist binding has been localized to an extracellular domain whose core is homologous to the bacterial periplasmic binding proteins (PBP). We have established routine, baculovirus-mediated expression of a complete ligand-binding domain construct at the 10-L scale, yielding 10,40 milligrams of purified protein. This construct contains peptides that lie outside the PBP-homologous core and that connect the domain core to the transmembrane domains of the channel and to the N-terminal ,X'-domain. These linker peptides have been implicated in modulating channel physiology. Such extended constructs have proven difficult to express in bacteria, but the protein described here is stable and monomeric. Isothermal titration calorimetry reveals that glutamate binding to the domain involves a substantial heat capacity change and that at physiological temperatures, the reaction is both entropically and enthalpically favorable. [source] Late postnatal maturation of excitatory synaptic transmission permits adult-like expression of hippocampal-dependent behaviorsHIPPOCAMPUS, Issue 5 2005Theodore C. Dumas Abstract Sensorimotor systems in altricial animals mature incrementally during early postnatal development, with complex cognitive abilities developing late. Of prominence are cognitive processes that depend on an intact hippocampus, such as contextual,configural learning, allocentric and idiocentric navigation, and certain forms of trace conditioning. The mechanisms that regulate the delayed maturation of the hippocampus are not well understood. However, there is support for the idea that these behaviors come "on line" with the final maturation of excitatory synaptic transmission. First, by providing a timeline for the first behavioral expression of various forms of learning and memory, this study illustrates the late maturation of hippocampal-dependent cognitive abilities. Then, functional development of the hippocampus is reviewed to establish the temporal relationship between maturation of excitatory synaptic transmission and the behavioral evidence of adult-like hippocampal processing. These data suggest that, in rats, mechanisms necessary for the expression of adult-like synaptic plasticity become available at around 2 postnatal weeks of age. However, presynaptic plasticity mechanisms, likely necessary for refinement of the hippocampal network, predominate and impede information processing until the third postnatal week. © 2005 Wiley-Liss, Inc. [source] Bi-directional modulation of fast inhibitory synaptic transmission by leptinJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Natasha Solovyova Abstract The hormone leptin has widespread actions in the CNS. Indeed, leptin markedly influences hippocampal excitatory synaptic transmission and synaptic plasticity. However, the effects of leptin on fast inhibitory synaptic transmission in the hippocampus have not been evaluated. Here, we show that leptin modulates GABAA receptor-mediated synaptic transmission onto hippocampal CA1 pyramidal cells. Leptin promotes a rapid and reversible increase in the amplitude of evoked GABAA receptor-mediated inhibitory synaptic currents (IPSCs); an effect that was paralleled by increases in the frequency and amplitude of miniature IPSCs, but with no change in paired pulse ratio or coefficient of variation, suggesting a post-synaptic expression mechanism. Following washout of leptin, a persistent depression (inhibitory long-lasting depression) of evoked IPSCs was observed. Whole-cell dialysis or bath application of inhibitors of phosphoinositide 3 (PI 3)-kinase or Akt prevented leptin-induced enhancement of IPSCs indicating involvement of a post-synaptic PI 3-kinase/Akt-dependent pathway. In contrast, blockade of PI 3-kinase or Akt activity failed to alter the ability of leptin to induce inhibitory long-lasting depression, suggesting that this process is independent of PI 3-kinase/Akt. In conclusion these data indicate that the hormone leptin bi-directionally modulates GABAA receptor-mediated synaptic transmission in the hippocampus. These findings have important implications for the role of this hormone in regulating hippocampal pyramidal neuron excitability. [source] The glutamatergic nature of TRPV1-expressing neurons in the spinal dorsal hornJOURNAL OF NEUROCHEMISTRY, Issue 1 2009Hong-Yi Zhou Abstract The transient receptor potential vanilloid receptor 1 (TRPV1) is expressed on primary afferent terminals and spinal dorsal horn neurons. However, the neurochemical phenotypes and functions of TRPV1-expressing post-synaptic neurons in the spinal cord are not clear. In this study, we tested the hypothesis that TRPV1-expressing dorsal horn neurons are glutamatergic. Immunocytochemical labeling revealed that TRPV1 and vesicular glutamate transporter-2 were colocalized in dorsal horn neurons and their terminals in the rat spinal cord. Resiniferatoxin (RTX) treatment or dorsal rhizotomy ablated TRPV1-expressing primary afferents but did not affect TRPV1- and vesicular glutamate transporter-2-expressing dorsal horn neurons. Capsaicin significantly increased the frequency of glutamatergic spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in almost all the lamina II neurons tested in control rats. In RTX-treated or dorsal rhizotomized rats, capsaicin still increased the frequency of spontaneous excitatory post-synaptic currents and miniature excitatory post-synaptic currents in the majority of neurons examined, and this effect was abolished by a TRPV1 blocker or by non-NMDA receptor antagonist. In RTX-treated or in dorsal rhizotomized rats, capsaicin also produced an inward current in a subpopulation of lamina II neurons. However, capsaicin had no effect on GABAergic and glycinergic spontaneous inhibitory post-synaptic currents of lamina II neurons in RTX-treated or dorsal rhizotomized rats. Collectively, our study provides new histological and functional evidence that TRPV1-expressing dorsal horn neurons in the spinal cord are glutamatergic and that they mediate excitatory synaptic transmission. This finding is important to our understanding of the circuitry and phenotypes of intrinsic dorsal horn neurons in the spinal cord. [source] Vasopressin Preferentially Depresses Excitatory Over Inhibitory Synaptic Transmission in the Rat Supraoptic Nucleus In VitroJOURNAL OF NEUROENDOCRINOLOGY, Issue 4 2000Kombian1 Endogenous arginine-vasopressin (AVP) in the supraoptic nucleus is known to decrease the firing rate of some supraoptic nucleus neurones. To determine a possible mechanism by which this locally released AVP produces this change in neuronal excitability, we investigated the effects of AVP on evoked excitatory (e.p.s.c.) and inhibitory post-synaptic (i.p.s.c.) responses recorded in magnocellular neurones in a hypothalamic slice preparation, using the perforated-patch recording technique. Our data show that AVP produces a dose-dependent decrease in the evoked e.p.s.c. in about 80% of magnocellular neurones tested with an estimated EC50 of about 0.9 ,M. The maximum decrease in e.p.s.c. amplitude was about 31% of control and was obtained with an AVP concentration of 2 ,M. The AVP-induced synaptic depression was blocked by Manning Compound (MC), a non-selective antagonist of oxytocin (OXT) and vasopressin (AVP) receptors, but not by a selective OXT receptor antagonist. It was not mimicked by desmopressin (ddAVP), a V2-receptor subtype agonist. By contrast, AVP used at the same concentration (2 ,M), had no global effect on pharmacologically isolated i.p.s.c.s in the majority of magnocellular neurones tested. These results show that AVP acts in the supraoptic nucleus to reduce excitatory synaptic transmission to magnocellular neurones by activating a non-OXT receptor, presumably the V1 receptor subtype. [source] Pain relief by gabapentin and pregabalin via supraspinal mechanisms after peripheral nerve injuryJOURNAL OF NEUROSCIENCE RESEARCH, Issue 15 2008Mitsuo Tanabe Abstract The antihypersensitivity actions of gabapentin and pregabalin have been well characterized in a large number of studies, although the underlying mechanisms have yet to be defined. We have been focusing on the supraspinal structure as a possible site for their action and have demonstrated that intracerebroventricular (i.c.v.) administration of gabapentin and pregabalin indeed decreases thermal and mechanical hypersensitivity in a murine chronic pain model involving partial ligation of the sciatic nerve. This novel supraspinally mediated analgesic effect was markedly suppressed by either depletion of central noradrenaline (NA) or blockade of spinal ,2 -adrenergic receptors. Moreover, i.c.v. injection of gabapentin and pregabalin increased spinal NA turnover in mice only after peripheral nerve injury. In locus coeruleus (LC) neurons in brainstem slices prepared from mice after peripheral nerve injury, gabapentin reduced the ,-aminobutyric acid (GABA) type A receptor-mediated inhibitory postsynaptic currents (IPSCs). Glutamate-mediated excitatory synaptic transmission was hardly affected. Moreover, gabapentin did not reduce IPSCs in slices taken from mice given a sham operation. Although gabapentin altered neither the amplitude nor the frequency of miniature IPSCs, it reduced IPSCs together with an increase in the paired-pulse ratio, suggesting that gabapentin acts on the presynaptic GABAergic nerve terminals in the LC. Together, the data suggest that gabapentin presynaptically reduces GABAergic synaptic transmission, thereby removing the inhibitory influence on LC neurons only in neuropathic pain states, leading to activation of the descending noradrenergic system. © 2008 Wiley-Liss, Inc. [source] Heat opens axon initial segment sodium channels: A febrile seizure mechanism?,ANNALS OF NEUROLOGY, Issue 2 2009Evan A. Thomas PhD Objective A number of hypotheses have been put forward as to why humans respond to fever by seizing. The current leading hypotheses are that respiratory alkalosis produces an as yet unidentified change in neural excitability or that inflammatory mediators potentiate excitatory synaptic transmission. However, it is well known that ion channel gating rates increase with increased temperature. Furthermore, skeletal and cardiac sodium channel activation can be temperature sensitive in some situations. We measured the temperature sensitivity of the brain sodium channel, NaV1.2, to determine whether febrile temperatures might produce a direct increase in neuronal excitability. Methods The effect of temperature on NaV1.2 electrophysiological properties was measured in a transfected mammalian cell line. The subcellular location of NaV1.2 in the mouse brain was ascertained using antibodies against NaV1.2 and ankyrin-G. Computer simulation of a hippocampal granule cell model was used to predict the effect of temperature on action potential firing. Results As well as the expected increase in gating rates, the voltage dependence of activation became 7.6mV more negative when the temperature was increased from 37°C to 41°C. NaV1.2 was localized to the axon initial segment in hippocampal and cortical neurons. Computer simulation showed that increased gating rates and the more negative activation dramatically increase neuronal excitability. Interpretation The direct effect of heat on ion channels localized to the site of action potential initiation potentially causes a profound increase in neuronal excitability. This is likely to contribute to febrile seizure genesis. Ann Neurol 2009;66:219,226 [source] 4415: Biochemical methods and X-ray based imaging strategies to evaluate retinal glucose metabolismACTA OPHTHALMOLOGICA, Issue 2010C POITRY-YAMATEArticle first published online: 23 SEP 2010 Purpose Evaluating the coordinated energy metabolism between neurons and glia in situ as a means to evaluate retinal glucose metabolism and function. Methods The imaging of metals conjugated to sugar substrates or metals linked to compounds that affect glycolysis were detected using synchrotron-based low and high energy x-ray fluorescence imaging. X-ray fluorescence maps with <1 micron resolution were placed in a morphological context using simultaneously acquired transmission images of the preparation. Spectrophotometric enzymatic microassays with high selectivity and sensitivity were performed to confirm the intracellular incorporation and metabolism of the delivered substances. Results In the dark-adapted rat retina, glucose transport and phosphorylation were specifically localized to the Müller glia in situ and an activated glycolysis was not measurable in neurons. Glial glucose metabolism was moreover coordinated with excitatory synaptic transmission in the mid to outer retina. Conclusion Given that oxygen metabolism predominates in neurons and that oxidative metabolism is fuelled by glucose metabolism, fuel transport obligatorily occurs from glia to neurons in intact healthy retina. Combining x-ray techniques with micron to submicron resolution and biochemical microassays with nM sensitivity offers: (1) a unique experimental strategy to evaluate retinal and cerebral energy metabolism and compartmentation at the cellular level in situ; and (2) is important to the interpretation of images using in vivo functional imaging techniques in the clinic. [source] | |||||||||||||