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Synaptic Responses (synaptic + response)
Selected AbstractsCholinergic suppression of excitatory synaptic responses in layer II of the medial entorhinal cortexHIPPOCAMPUS, Issue 2 2007Bassam N. Hamam Abstract Theta-frequency (4,12 Hz) electroencephalographic activity is thought to play a role in mechanisms mediating sensory and mnemonic processing in the entorhinal cortex and hippocampus, but the effects of acetylcholine on excitatory synaptic inputs to the entorhinal cortex are not well understood. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of the piriform (olfactory) cortex were recorded in the medial entorhinal cortex during behaviors associated with theta activity (active mobility) and were compared with those recorded during nontheta behaviors (awake immobility and slow wave sleep). Synaptic responses were smaller during behavioral activity than during awake immobility and sleep, and responses recorded during movement were largest during the negative phase of the theta rhythm. Systemic administration of cholinergic agonists reduced the amplitude of fEPSPs, and the muscarinic receptor blocker scopolamine strongly enhanced fEPSPs, suggesting that the theta-related suppression of fEPSPs is mediated in part by cholinergic inputs. The reduction in fEPSPs was investigated using in vitro intracellular recordings of EPSPs in Layer II neurons evoked by stimulation of Layer I afferents. Constant bath application of the muscarinic agonist carbachol depolarized membrane potential and suppressed EPSP amplitude in Layer II neurons. The suppression of EPSPs was not associated with a substantial change in input resistance, and could not be accounted for by a depolarization-induced reduction in driving force on the EPSP. The GABAA receptor-blocker bicuculline (50 ,M) did not prevent the cholinergic suppression of EPSPs, suggesting that the suppression is not dependent on inhibitory mechanisms. Paired-pulse facilitation of field and intracellular EPSPs were enhanced by carbachol, indicating that the suppression is likely due to inhibition of presynaptic glutamate release. These results indicate that, in addition to well known effects on postsynaptic conductances that increase cellular excitability, cholinergic activation in the entorhinal cortex results in a strong reduction in strength of excitatory synaptic inputs from the piriform cortex. © 2006 Wiley-Liss, Inc. [source] An antibody to synaptotagmin I facilitates synaptic transmissionEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2007Shao-Ying Hua Abstract Proper functioning of the nervous system requires precise control of neurotransmitter release. Synaptotagmin, a synaptic vesicle protein, is crucial for the temporal control of neurotransmitter release. The mechanism of synaptotagmin function is still under debate. To investigate the mechanism by which synaptotagmin controls neurotransmitter release, we injected an antibody of rat synaptotagmin I into a crayfish motor axon. We found that the antibody enhanced synaptic transmission at crayfish neuromuscular junctions by increasing the amplitude of the evoked synaptic response. This effect was antibody-dose dependent. The antibody also reduced the rise time of the synaptic potentials. These effects were accompanied by a reduction in the Hill coefficient for Ca2+ -dependence of synaptic transmission. Our findings support the hypothesis that synaptotagmin inhibits neurotransmitter release in the absence of Ca2+. [source] Chronic cocaine sensitizes striatal GABAergic synapses to the stimulation of cannabinoid CB1 receptorsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2007Diego Centonze Abstract Behavioural studies indicate that cannabinoid receptors are implicated in cocaine addiction. The synaptic underpinning of cocaine,cannabinoid receptor interaction is however, obscure. We have studied electrophysiologically the sensitivity of cannabinoid receptors modulating synaptic transmission in the striatum of rats exposed to cocaine. One-day treatment with cocaine did not modify the synaptic response to HU210, a cannabinoid CB1 receptor agonist. Seven days cocaine-treatment, conversely, caused conditioned place preference, and sensitized striatal GABAergic synapses to the presynaptic effect of cannabinoid CB1 receptor stimulation. The cannabinoid receptor-induced modulation of glutamate transmission was unaltered by cocaine. Furthermore, the effects of chronic cocaine on cannabinoid-mediated regulation of striatal GABA synapses were attenuated one week after the discontinuation of cocaine, and absent two weeks later, indicating the progressive reversibility of the adaptations of cannabinoid system during abstinence of drug consumption. Our data support the concept that modulation of cannabinoid receptors might be useful against drug abuse. [source] Excitatory synaptic potentials in spastic human motoneurons have a short rise-timeMUSCLE AND NERVE, Issue 1 2005Nina L. Suresh PhD Abstract This study assessed whether changes in size or time-course of excitatory postsynaptic potentials (EPSPs) in motoneurons innervating spastic muscle could induce a greater synaptic response, and thereby contribute to reflex hyperexcitability. We compared motor unit (MU) firing patterns elicited by tendon taps applied to both spastic and contralateral (nonspastic) biceps brachii muscle in hemiparetic stroke subjects. Based on recordings of 115 MUs, significantly shortened EPSP rise times were present on the spastic side, but with no significant differences in estimated EPSP amplitude. These changes may contribute to hyperexcitable reflex responses at short latency, but the EPSP amplitude changes appear insufficient to account for global differences in reflex excitability. Muscle Nerve, 2005 [source] Cyclosporine Induces Epileptiform Activity in an In Vitro Seizure ModelEPILEPSIA, Issue 3 2000Michael Wong Summary: Purpose: Cyclosporine (CSA) toxicity represents a common cause of seizures in transplant patients, but the specific mechanisms by which CSA induces seizures are unknown. Although CSA may promote seizure activity by various metabolic, toxic, vascular, or structural mechanisms, CSA also has been hypothesized to modulate neuronal excitability directly. The objective of this study was to determine if CSA exerts direct epileptogenic actions on neurons in an in vitro seizure model. Methods: Combined hippocampal-entorhinal cortex slices from juvenile rats were exposed directly to artificial cerebro-spinal fluid (ACSF) containing either (a) 1.0 mM magnesium sulfate (control), (b) 1.0 mM sodium sulfate (low-magnesium), or (c) 1.0 mM magnesium sulfate + CSA (1,000,10,000 ng/ml). Spontaneous and evoked extracellular field potentials were recorded simultaneously from the dentate gyrus (DG) and CA3 hippocampal regions. Evoked synaptic responses were elicited by stimulation of the entorhinal cortex/perforant pathway. Results: CSA elicited spontaneous or stimulation-induced epileptiform activity in the DG or CA3 region of ,40% of slices, consisting of brief repetitive "interictal" discharges or prolonged stereotypical "ictal" discharges. Mean latency to epileptiform activity was ,100 min after onset of CSA application. The interictal discharges were inhibited by the non-NMDA antagonist, NBQX. Similar epileptiform activity was observed in low-magnesium ACSF without CSA. In control ACSF alone, epileptiform activity was not seen, except for rare spontaneous potentials in the DG. Conclusions: Direct effects of CSA on neuronal excitability and synaptic transmission may contribute to seizures seen in clinical CSA neurotoxicity. [source] N -methyl- d -aspartate receptor- and metabotropic glutamate receptor-dependent long-term depression are differentially regulated by the ubiquitin-proteasome systemEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 8 2009Ami Citri Abstract Long-term depression (LTD) in CA1 pyramidal neurons can be induced by activation of either N -methyl- d -aspartate receptors (NMDARs) or metabotropic glutamate receptors (mGluRs), both of which elicit changes in synaptic efficacy through ,-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate receptor (AMPAR) endocytosis. To address the role of the ubiquitin-proteasome system in regulating AMPAR endocytosis during these forms of LTD, we examined the effects of pharmacological inhibitors of proteasomal degradation and protein ubiquitination on endocytosis of glutamate receptor 1 (GluR1) -containing AMPARs in dissociated rat hippocampal cultures as well as LTD of excitatory synaptic responses in acute rat hippocampal slices. Our findings suggest that the contribution of the ubiquitin-proteasome system to NMDAR-induced vs. mGluR-induced AMPAR endocytosis and the consequent LTD differs significantly. NMDAR-induced AMPAR endocytosis and LTD occur independently of proteasome function but appear to depend, at least in part, on ubiquitination. In contrast, mGluR-induced AMPAR endocytosis and LTD are enhanced by inhibition of proteasomal degradation, as well as by the inhibitor of protein ubiquitination. Furthermore, the decay of mGluR-induced membrane depolarization and Erk activation is delayed following inhibition of either ubiquitination or proteasomal degradation. These results suggest that, although NMDAR-dependent LTD may utilize ubiquitin as a signal for AMPAR endocytosis, mGluR-induced signaling and LTD are limited by a feedback mechanism that involves the ubiquitin-proteasome system. [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] Effects of M-current modulators on the excitability of immature rat spinal sensory and motor neuronesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005I. Rivera-Arconada Abstract M-currents have been shown to control neuronal excitability in a variety of central and peripheral neurones. Here we studied the effects of specific M-current modulators on the excitability of spinal neurones and their response to synaptic activation. Experiments were performed in vitro using the hemisected spinal cord from 7- to 11-day-old rats. Intracellular recordings were obtained from lumbar deep dorsal horn and motor neurones. Neuronal excitability was assessed by applying outward current pulses and synaptic responses were elicited by activation of a lumbar dorsal root. The M-current antagonist 10,10- bis(4-pyridinylmethyl)-9(10H)-anthracenone (XE-991) and the agonist retigabine were superfused at 10 µm. Retigabine produced hyperpolarization and a large decrease in the excitability of motor (7/7) and dorsal horn neurones (11/12). The effects of retigabine were fully reversed by XE-991. XE-991 induced depolarization of most neurones tested and a large increase in the excitability of motor neurones (7/7) but only a weak increase in the excitability of a proportion of dorsal horn neurones (4/10). The effects of XE-991 were partly reversed by retigabine. Consistent with their effects on neuronal excitability, retigabine showed a general depressant effect on synaptic transmission, whereas XE-991 showed the opposite tendency to potentiate responses to dorsal root stimulation, particularly in motor neurones. The results show that retigabine can depress spinal excitability and the transmission of nociceptive information. Results also indicate a post-synaptic expression of functional M-currents in most motor neurones and a considerable proportion of deep dorsal horn neurones. [source] Dopamine D1-like receptor modulates layer- and frequency-specific short-term synaptic plasticity in rat prefrontal cortical neuronsEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2005Clint E. Young Abstract The mesocortical dopamine (DA) input to the prefrontal cortex (PFC) is crucial for processing short-term working memory (STWM) to guide forthcoming behavior. Short-term plasticity-like post-tetanic potentiation (PTP, < 3 min) and short-term potentiation (STP, <,10 min) may underlie STWM. Using whole-cell voltage-clamp recordings, mixed glutamatergic excitatory postsynaptic currents (EPSCs) evoked by layer III or layer V stimulation (0.5 or 0.067 Hz) were recorded from layer V pyramidal neurons. With 0.5 Hz basal stimulation of layer III, brief tetani (2 × 50 Hz) induced a homosynaptic PTP (decayed: ,1 min). The D1-like antagonist SCH23390 (1 µm) increased the PTP amplitude and decay time without inducing changes to the tetanic response. The tetani may evoke endogenous DA release, which activates a presynaptic D1-like receptor to inhibit glutamate release to modulate PTP. With a slower (0.067 Hz) basal stimulation, the same tetani induced STP (lasting ,4 min, but only at 2× intensity only) that was insignificantly suppressed by SCH23390. With stimulation of layer-V,V inputs at 0.5 Hz, layer V tetani yielded inconsisitent responses. However, at 0.067 Hz, tetani at double the intensity resulted in an STP (lasting ,6 min), but a long-term depression after SCH23390 application. Endogenous DA released by tetanic stimulation can interact with a D1-like receptor to induce STP in layer V,V synapses that receive slower (0.067 Hz) frequency inputs, but suppresses PTP at layer III,V synapses that receive higher (0.5 Hz) frequency inputs. This D1-like modulation of layer- and frequency-specific synaptic responses in the PFC may contribute to STWM processing. [source] Presynaptic source of quantal size variability at GABAergic synapses in rat hippocampal neurons in cultureEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2004Andrea Barberis Abstract The variability of quantal size depends on both presynaptic (profile of the neurotransmitter concentration in the cleft) and postsynaptic (number and gating properties of postsynaptic receptors) factors. Here we have examined the possibility that at nonsaturated synapses in cultured hippocampal neurons, changes in both the transmitter concentration peak and its clearance from the synaptic cleft may influence the variability of spontaneous miniature synaptic GABAergic currents (mIPSCs). We found that, in contrast to the slow-off GABAA receptor antagonist bicuculline, fast-off competitive antagonists such as SR-95103 and TPMPA differentially blocked small and large mIPSCs. In the presence of flurazepam, a drug believed to increase the affinity of GABA for GABAAR, small mIPSCs were enhanced more efficiently than large events. Moreover, the addition of dextran, which increases the viscosity of the extracellular fluid, preferentially increased small mIPSCs with respect to large ones. These observations suggest that changes in the concentration peak and the speed of GABA clearance in the cleft may be an important source of synaptic variability. The study of the correlation between peak amplitude and kinetics of mIPSCs allowed determination of the relative contribution of transmitter peak concentration vs. time of GABA clearance. Small synaptic responses were associated with fast onset and decay kinetics while large amplitude currents were asociated with slow kinetics, indicating a crucial role for GABA synaptic clearance in variability of mIPSCs. By using model simulations we were able to estimate the range of variability of both the concentration and the speed of clearance of the GABA transient in the synaptic cleft. [source] Synaptic and non-synaptic mechanisms of amygdala recruitment into temporolimbic epileptiform activitiesEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 10 2003Julia Klueva Abstract Lateral amygdala (LA) activity during synchronized-epileptiform discharges in temporolimbic circuits was investigated in rat horizontal slices containing the amygdala, hippocampus (Hip), perirhinal (Prh) and lateral entorhinal (LEnt) cortex, through multiple-site extra- and intracellular recording techniques and measurement of the extracellular K+ concentration. Application of 4-aminopyridine (50 µm) induced epileptiform discharges in all regions under study. Slow interictal-like burst discharges persisted in the Prh/LEnt/LA after disconnection of the Hip, seemed to originate in the Prh as shown from time delay analyses, and often preceded the onset of ictal-like activity. Disconnection of the amygdala resulted in de-synchronization of epileptiform discharges in the LA from those in the Prh/LEnt. Interictal-like activity was intracellularly reflected in LA projection neurons as ,-aminobutyric acid (GABA)A/B receptor-mediated synaptic responses, and depolarizing electrogenic events (spikelets) residing on the initial phase of the GABA response. Spikelets were considered antidromically conducted ectopic action potentials generated at axon terminals, as they were graded in amplitude, were not abolished through hyperpolarizing membrane responses (which effectively blocked evoked orthodromic action potentials), lacked a clear prepotential or synaptic potential, were not affected through blockers of gap junctions, and were blocked through remote application of tetrodotoxin at putative target areas of LA projection neurons. Remote application of a GABAB receptor antagonist facilitated spikelet generation. A transient elevation in the extracellular K+ level averaging 3 mm above baseline occurred in conjunction with interictal-like activity in all areas under study. We conclude that interictal-like discharges in the LA/LEnt/Prh spread in a predictable manner through the synaptic network with the Prh playing a leading role. The rise in extracellular K+ may provide a depolarizing mechanism for recruitment of interneurons and generation of ectopic action potentials at axon terminals of LA projection neurons. Antidromically conducted ectopic action potentials may provide a spreading mechanism of seizure activity mediated by diffuse axonal projections of LA neurons. [source] Hippocampal long-term depression as an index of spatial working memoryEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 5 2002Kazuhito Nakao Abstract Long-term potentiation (LTP), a form of synaptic plasticity in the hippocampus, is a cellular model for the neural basis of learning and memory, but few studies have investigated the contribution of long-term depression (LTD), a counterpart of LTP. To address the possible relationship between hippocampal LTD and spatial performance, the spatial cognitive ability of a rat was assessed in a spontaneous alternation test and, thereafter, LTD in response to low-frequency burst stimulation (LFBS) was monitored in the dentate gyrus of the same rat under anaesthesia. To enhance a divergence in the ability for spatial performance, some of the animals received fimbria,fornix (FF) transection 14 days before the experiments. LTD was reliably induced by application of LFBS to the medial perforant path of intact rats, while no apparent LTD was elicited in rats with FF lesions. The behavioural parameters of spatial memory showed a significant correlation with the magnitude of LTD. We found no evidence that the cognitive ability correlated with other electrophysiological parameters, e.g. basal synaptic responses, stimulus intensity to produce half-maximal responses, paired-pulse facilitation or paired-pulse depression. These results suggest that the magnitude of LTD in the dentate gyrus serves as a reliable index of spatial cognitive ability, providing insights into the functional significance of hippocampal LTD. [source] Cholinergic suppression of excitatory synaptic responses in layer II of the medial entorhinal cortexHIPPOCAMPUS, Issue 2 2007Bassam N. Hamam Abstract Theta-frequency (4,12 Hz) electroencephalographic activity is thought to play a role in mechanisms mediating sensory and mnemonic processing in the entorhinal cortex and hippocampus, but the effects of acetylcholine on excitatory synaptic inputs to the entorhinal cortex are not well understood. Field excitatory postsynaptic potentials (fEPSPs) evoked by stimulation of the piriform (olfactory) cortex were recorded in the medial entorhinal cortex during behaviors associated with theta activity (active mobility) and were compared with those recorded during nontheta behaviors (awake immobility and slow wave sleep). Synaptic responses were smaller during behavioral activity than during awake immobility and sleep, and responses recorded during movement were largest during the negative phase of the theta rhythm. Systemic administration of cholinergic agonists reduced the amplitude of fEPSPs, and the muscarinic receptor blocker scopolamine strongly enhanced fEPSPs, suggesting that the theta-related suppression of fEPSPs is mediated in part by cholinergic inputs. The reduction in fEPSPs was investigated using in vitro intracellular recordings of EPSPs in Layer II neurons evoked by stimulation of Layer I afferents. Constant bath application of the muscarinic agonist carbachol depolarized membrane potential and suppressed EPSP amplitude in Layer II neurons. The suppression of EPSPs was not associated with a substantial change in input resistance, and could not be accounted for by a depolarization-induced reduction in driving force on the EPSP. The GABAA receptor-blocker bicuculline (50 ,M) did not prevent the cholinergic suppression of EPSPs, suggesting that the suppression is not dependent on inhibitory mechanisms. Paired-pulse facilitation of field and intracellular EPSPs were enhanced by carbachol, indicating that the suppression is likely due to inhibition of presynaptic glutamate release. These results indicate that, in addition to well known effects on postsynaptic conductances that increase cellular excitability, cholinergic activation in the entorhinal cortex results in a strong reduction in strength of excitatory synaptic inputs from the piriform cortex. © 2006 Wiley-Liss, Inc. [source] Latest view on the mechanism of action of deep brain stimulation,MOVEMENT DISORDERS, Issue 15 2008Constance Hammond PhD Abstract How does deep brain stimulation (DBS) applied at high frequency (100 Hz and above, HFS) in diverse points of cortico-basal ganglia thalamo-cortical loops alleviate symptoms of neurological disorders such as Parkinson's disease, dystonia, and obsessive compulsive disorders? Do the effects of HFS stem solely or even largely from local effects on the stimulated brain structure or are they also mediated by actions of HFS on distal structures? Indeed, HFS as an extracellular stimulation is expected to activate subsets of both afferent and efferent axons, leading to antidromic spikes that collide with ongoing spontaneous ones and orthodromic spikes that evoke synaptic responses in target neurons. The present review suggests that HFS interfere with spontaneous pathological patterns by introducing a regular activity in several nodal points of the network. Therefore, the best site of implantation of the HFS electrode may be in a region where the HFS-driven activity spreads to most of the identified, dysrhythmic, neuronal populations without causing additional side effects. This should help tackling the most difficult issue namely, how does the regular HFS-driven activity that dampens the spontaneous pathological one, restore neuronal processing along cortico-basal ganglia-thalamo-cortical loops? © 2008 Movement Disorder Society [source] Synaptic heterogeneity between mouse paracapsular intercalated neurons of the amygdalaTHE JOURNAL OF PHYSIOLOGY, Issue 1 2007Raffaella Geracitano GABAergic medial paracapsular intercalated (Imp) neurons of amygdala are thought of as playing a central role in fear learning and extinction. We report here that the synaptic network formed by these neurons exhibits distinct short-term plastic synaptic responses. The success rate of synaptic events evoked at a frequency range of 0.1,10 Hz varied dramatically between different connected cell pairs. Upon enhancing the frequency of stimulation, the success rate increased, decreased or remained constant, in a similar number of cell pairs. Such synaptic heterogeneity resulted in inhibition of the firing of the postsynaptic neurons with different efficacies. Moreover, we found that the different synaptic weights were mainly determined by diversity in presynaptic release probabilities rather than postsynaptic changes. Sequential paired recording experiments demonstrated that the same presynaptic neuron established the same type of synaptic connections with different postsynaptic neurons, suggesting the absence of target-cell specificity. Conversely, the same postsynaptic neuron was contacted by different types of synaptic connections formed by different presynaptic neurons. A detailed anatomical analysis of the recorded neurons revealed discrete and unexpected peculiarities in the dendritic and axonal patterns of different cell pairs. In contrast, several intrinsic electrophysiological responses were homogeneous among neurons, and synaptic failure counts were not affected by presynaptic cannabinoid 1 or GABAB receptors. We propose that the heterogeneous functional connectivity of Imp neurons, demonstrated by this study, is required to maintain the stability of firing patterns which is critical for the computational role of the amygdala in fear learning and extinction. [source] Early expression of AMPA receptors and lack of NMDA receptors in developing rat climbing fibre synapsesTHE JOURNAL OF PHYSIOLOGY, Issue 3 2005Philippe Lachamp Whether nascent glutamatergic synapses acquire their AMPA receptors constitutively or via a regulated pathway triggered by pre-existing NMDA receptor activation is still an open issue. Here, we provide evidence that some glutamatergic synapses develop without expressing NMDA receptors. Using immunocytochemistry, we showed that synapses between developing rat climbing fibres and Purkinje cells expressed GluR2-containing AMPA receptors as soon as they were formed (i.e. on embryonic day 19) but never carried detectable NMDA receptors. This was confirmed by electrophysiological recordings. Excitatory synaptic currents were recorded in Purkinje cells as early as P0. However, no NMDA receptor-mediated component was found in either spontaneous or evoked synaptic responses. In addition, we ruled out a possible role of extrasynaptic NMDA receptors by showing that AMPA receptor clustering at nascent climbing fibre synapses was not modified by chronic in utero NMDA receptor blockade. [source] AMPA-sst2 somatostatin receptor interaction in rat hypothalamus requires activation of nmda and/or metabotropic glutamate receptors and depends on intracellular calciumTHE JOURNAL OF PHYSIOLOGY, Issue 1 2003Stéphane Peineau Modulation of glutamatergic transmission by neuropeptides is an essential aspect of neuronal network activity. Activation of the hypothalamic somatostatin sst2 receptor subtype by octreotide decreases AMPA glutamate responses, indicating a central link between a neurohormonal and neuromodulatory peptide and the main hypothalamic fast excitatory neurotransmitter. In mediobasal hypothalamic slices, sst2 activation inhibits the AMPA component of glutamatergic synaptic responses but is ineffective when AMPA currents are pharmacologically isolated. In mediobasal hypothalamic cultures, the decrease of AMPA currents induced by octreotide requires a concomitant activation of sst2 receptors with either NMDA and/or metabotropic glutamate receptors. This modulation depends on changes in intracellular calcium concentration induced by calcium flux through NMDA receptors or calcium release from intracellular stores following metabotropic glutamate receptor activation. These results highlight an unusual regulatory mechanism in which the simultaneous activation of at least three different types of receptor is necessary to allow somatostatin-induced modulation of fast synaptic glutamatergic transmission in the hypothalamus. [source] Effects of endomorphin on substantia gelatinosa neurons in rat spinal cord slicesBRITISH JOURNAL OF PHARMACOLOGY, Issue 6 2003Su-Ying Wu Whole-cell patch recordings were made from substantia gelatinosa (SG) neurons in transverse lumbar spinal cord slices of 15- to 30-day-old rats. Endomorphin 1 (EM-1) or EM-2 (10 ,M) hyperpolarized or induced an outward current in 26 of the 66 SG neurons. The I,V relationship showed that the peptide activates an inwardly rectifying K+ current. EM-1 or EM-2 (0.3,10 ,M) suppressed short-latency excitatory postsynaptic currents (EPSCs) and long-latency inhibitory postsynaptic currents (IPSCs) in nearly all SG neurons tested or short-latency IPSCs in six of the 10 SG neurons. [Met5] enkephalin or [D -Ala2, N -Me-Phe4, Gly5 -ol]-enkephalin (DAMGO) (1,10 ,M) depressed EPSCs and IPSCs. EM-1 or EM-2 depressed synaptic responses without causing a significant change in holding currents or inward currents induced by glutamate. Glutamate also evoked a short-latency outward current in five SG neurons or a biphasic current in two neurons; the outward current was blocked by tetrodotoxin (TTX, 0.3 ,M) or bicuculline (10 ,M). EM-1 or DAMGO (1 or 5 ,M) attenuated the glutamate-evoked outward or biphasic currents in four of the seven SG neurons. EM-1 (1 ,M) reduced the frequency, but not the amplitude of miniature EPSCs or miniature IPSCs. Naloxone (1 ,M) or the selective , -opioid receptor antagonist , -funaltrexamine (, -FNA, 25 ,M) antagonized the action of EM; EM-induced hyperpolarizations persisted in the presence of the , -opioid receptor antagonist (nor-binaltorphimine dihydrochloride, 1 ,M) and/or , -opioid receptor antagonist (naltrindole hydrochloride, 1 ,M). It may be concluded that EM acting on , -opioid receptors hyperpolarizes a population of SG neurons by activating an inwardly rectifying K+ current, and attenuates excitatory and inhibitory synaptic currents evoked in a population of SG neurons, probably by a presynaptic site of action. British Journal of Pharmacology (2003) 140, 1088,1096. doi:10.1038/sj.bjp.0705534 [source] | |||||||||||||