Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Excitatory Postsynaptic Potentials”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,009 records · Page 56Linked to original sources
PubMed1998

Acute intrahippocampal infusion of BDNF induces lasting potentiation of synaptic transmission in the rat dentate gyrus.

The effect of acute intrahippocampal infusion of brain-derived neurotrophic factor (BDNF) on synaptic transmission in the dentate gyrus was investigated in urethan-anesthetized rats. Medial perforant path-evoked field potentials were recorded in the dentate hilus and BDNF-containing buffer was infused (4 microl, 25 min) immediately above the dentate molecular layer. BDNF led to a slowly developing increase of the field excitatory postsynaptic potential (fEPSP) slope and population spike amplitude. The potentiation either reached a plateau level at approximately 2 h after BDNF infusion or continued to increase for the duration of experiment; the longest time point recorded was 10 h. Mean increases at 4 h after BDNF infusion were 62.2 and 224% for the fEPSP slope and population spike, respectively. No changes in responses were observed in controls receiving buffer medium only or buffer containing cytochrome C. BDNF-induced potentiation developed in the absence of epileptiform activity in the hippocampal electroencephalogram or changes in recurrent inhibition on granule cells as assessed by paired-pulse inhibition of the population spike. We conclude that exogenous BDNF induces a lasting potentiation of synaptic efficacy in the dentate gyrus of anesthetized adult rats.

Animals↗
PubMed2000

Synaptic stimulation of nicotinic receptors in rat sympathetic ganglia is followed by slow activation of postsynaptic potassium or chloride conductances.

Two slow currents have been described in rat sympathetic neurons during and after tetanization of the whole preganglionic input. Both effects are mediated by nicotinic receptors activated by native acetylcholine (ACh). A first current, indicated as IAHPsyn, is calcium dependent and voltage independent, and is consistent with an IAHP-type potassium current sustained by calcium ions accompanying the nicotinic synaptic current. The conductance activated by a standard synaptic train was approximately 3.6 nS per neuron; it was detected in isolation in 14 out of a 52-neuron sample. A novel current, IADPsyn, was described in 42/52 of the sample as a post-tetanic inward current, which increased in amplitude with increasing membrane potential negativity and exhibited a null-point close to the holding potential and the cell momentary chloride equilibrium potential. IADPsyn developed during synaptic stimulation and decayed thereafter according to a single exponential (mean tau = 148.5 ms) in 18 neurons or according to a two-exponential time course (tau = 51.8 and 364.9 ms, respectively) in 19 different neurons. The mean peak conductance activated was approximately 20 nS per neuron. IADPsyn was calcium independent, it was affected by internal and external chloride concentration, but was insensitive to specific blockers (anthracene-9-carboxylic acid, 9AC) of the chloride channels open in the resting neuron. It is suggested that gADPsyn represents a specific chloride conductance activatable by intense nicotinic stimulation; in some neurons it is even associated with single excitatory postsynaptic potentials (EPSCs). Both IAHP and IADPsyn are apparently devoted to reduce neuronal excitability during and after intense synaptic stimulation.

Animals↗
PubMed2003

Age and experience dependence of N-methyl-D-aspartate receptor-independent long-term potentiation in rat visual cortex.

Dark rearing prolongs the critical period for experience-dependent modification of visual cortical functions. To test whether long-term potentiation (LTP) could potentially underlie this modification, we studied the age and experience dependence of LTP, induced in layer 2/3 cells by layer 4 stimulation continued for 15 min at 2 Hz, in rat visual cortical slices. This LTP was independent of N-methyl-D-aspartate receptor (NMDAR) activation, but it likely required Ni(2+)-sensitive Ca(2+) channel activation for induction. LTP occurred frequently during development, but rarely in adulthood. Dark rearing prevented this developmental decline. These age- and experience-dependent changes were demonstrated in both excitatory postsynaptic potentials recorded from pyramidal cells under a local blockade of inhibition and extracellular field potentials. These results suggest the possible involvement of NMDAR-independent LTP in the experience-dependent development of visual cortex.

2-Amino-5-phosphonovalerate↗
PubMed2005

SK channels regulate excitatory synaptic transmission and plasticity in the lateral amygdala.

At glutamatergic synapses, calcium influx through NMDA receptors (NMDARs) is required for long-term potentiation (LTP); this is a proposed cellular mechanism underlying memory and learning. Here we show that in lateral amygdala pyramidal neurons, SK channels are also activated by calcium influx through synaptically activated NMDARs, resulting in depression of the synaptic potential. Thus, blockade of SK channels by apamin potentiates fast glutamatergic synaptic potentials. This potentiation is blocked by the NMDAR antagonist AP5 (D(-)-2-amino-5-phosphono-valeric acid) or by buffering cytosolic calcium with BAPTA. Blockade of SK channels greatly enhances LTP of cortical inputs to lateral amygdala pyramidal neurons. These results show that NMDARs and SK channels are colocalized at glutamatergic synapses in the lateral amygdala. Calcium influx through NMDARs activates SK channels and shunts the resultant excitatory postsynaptic potential. These results demonstrate a new role for SK channels as postsynaptic regulators of synaptic efficacy.

Amygdala↗
PubMed1999

Long-term potentiation at excitatory amino acid synapses on midbrain dopamine neurons.

Evidence suggests that a process analogous to long-term potentiation (LTP) may underlie the enhanced behavioural responses attending chronic administration of amphetamine and cocaine in animals (behavioural sensitization). Augmented excitatory amino acid (EAA)-mediated transmission at the level of midbrain dopamine neurons has been implicated as a change critical to the development of sensitization. Here we provide an initial demonstration that EAA synapses on dopamine neurons can undergo plasticity. Tetanic stimulation of the subthalamic nucleus induced a long-lasting increase (39.2 +/- 10.4%) in the amplitude of excitatory postsynaptic potentials recorded in dopamine neurons of the substantia nigra. This LTP, which did not occur in the presence of NMDA antagonists, may constitute the mechanism that lies at the heart of sensitization.

Animals↗
PubMed1988

The development of transmission at an identified molluscan synapse. I. The emergence of synaptic plasticities.

1. A monosynaptic, chemical synapse exists between two identified neurons in the subesophageal ganglia of the pulmonate mollusc, Achatina fulica. The snail undergoes a direct development, i.e., there is no intervening metamorphic period. The presynaptic (V2) and postsynaptic (RPr1) cells are two of the largest neurons found in the ganglia. The development of transmission at this synapse was studied from the last one-third of embryonic life to adulthood. 2. Synaptic transmission was studied by eliciting an action potential in V2 and recording the resultant excitatory postsynaptic potential (EPSP) in RPr1. In a train of repetitive stimuli, the ratio of the mean amplitude of the second EPSP to that of the first EPSP (EPSP2/EPSP1) is always greater than 1, indicating that short-term facilitation is present at all developmental ages studied. Following the initial short-term facilitation, embryonic synapses undergo a profound synaptic depression. Postembryonically there is a progressive increase in the amount of frequency facilitation with age, suggesting that the synapse shows a developmental trend towards an increased capacity for transmitter release. 3. In contrast to the progressive growth of frequency facilitation, the amplitude of the first EPSP in a series of responses (EPSP1) is not significantly related to age. 4. When transmitter release is reduced to approximately 25% of normal levels by a low-Ca2+/high-Mg2+ saline, the synaptic depression that is observed in the younger synapses disappears and is replaced by an adult-like frequency facilitation. 5. The adult synapse displays a phenomenon similar to posttetanic potentiation, which we refer to as the "retention of frequency facilitation." If an initial train of 150 stimuli at 0.2 Hz is followed by a second, identical train after an interval of 1 h, the postsynaptic response is greater during the second train than during the first. This phenomenon only becomes apparent in the second month after hatching, indicating that this separate synaptic plasticity develops at a different rate than does frequency facilitation.

Animals↗
PubMed2000

Role of EGR1 in hippocampal synaptic enhancement induced by tetanic stimulation and amputation.

Hippocampal neurons fire spikes when an animal is at a particular location or performs certain behaviors in a particular place, providing a cellular basis for hippocampal involvement in spatial learning and memory. In a natural environment, spatial memory is often associated with potentially dangerous sensory experiences such as noxious or painful stimuli. The central sites for such pain-associated memory or plasticity have not been identified. Here we present evidence that excitatory glutamatergic synapses within the CA1 region of the hippocampus may play a role in storing pain-related information. Peripheral noxious stimulation induced excitatory postsynaptic potentials (EPSPs) in CA1 pyramidal cells in anesthetized animals. Tissue/nerve injury caused a rapid increase in the level of the immediate-early gene product Egr1 (also called NGFI-A, Krox24, or zif/268) in hippocampal CA1 neurons. In parallel, synaptic potentiation induced by a single tetanic stimulation (100 Hz for 1 s) was enhanced after the injury. This enhancement of synaptic potentiation was absent in mice lacking Egr1. Our data suggest that Egr1 may act as an important regulator of pain-related synaptic plasticity within the hippocampus.

Amputation, Surgical↗
PubMed2000

Nicotinic acetylcholine receptor-mediated synaptic potentials in rat neocortex.

In the neocortex, fast excitatory synaptic transmission can typically be blocked by using excitatory amino acid (EAA) receptor antagonists. In recordings from layer II/III neocortical pyramidal neurons, we observed an evoked excitatory postsynaptic potential (EPSP) or current (EPSC) in the presence of EAA receptor antagonists (40-100 microM D-APV+20 microM CNQX, or 5 mM kynurenic acid) plus the GABA(A)-receptor antagonist bicuculline (BIC, 20 microM). This EAA-antagonist resistant EPSC was observed in about 70% of neurons tested. It had a duration of approximately 20 ms and an amplitude of 61.5+/-6.8 pA at -70 mV (n=35). The EAA-antagonist resistant EPSC current-voltage relation was linear and reversed near 0 mV (n=23). The nonselective nicotinic acetylcholine receptor (nAChR) antagonists dihydro-beta-erythroidine (DH beta E, 100 microM) or mecamylamine (50 microM) reduced EPSC amplitudes by 42 (n=20) and 33% (n=9), respectively. EPSC kinetics were not significantly changed by either antagonist. Bath application of 10 microM neostigmine, a potent acetylcholinesterase inhibitor, prolonged the EPSC decay time. EAA-antagonist resistant EPSCs were observed in the presence of antagonists of metabotropic glutamate, serotonergic (5-HT(3)) and purinergic (P2) receptors. The EAA-antagonist resistant EPSC appears to be due in part to activation of postsynaptic nAChRs. These results suggest the existence of functional synaptic nAChRs on pyramidal neurons in rat neocortex.

2-Amino-5-phosphonovalerate↗
PubMed1997

Interneurons in area CA1 stratum radiatum and stratum oriens remain functionally connected to excitatory synaptic input in chronically epileptic animals.

Past work has demonstrated a reduction of stimulus-evoked inhibitory input to hippocampal CA1 pyramidal cells in chronic models of temporal lobe epilepsy (TLE). It has been postulated that this reduction in inhibition results from impaired excitation of inhibitory interneurons. In this report, we evaluate the connectivity of area CA1 interneurons to their excitatory afferents in hippocampal-parahippocampal slices obtained from a rat model of chronic TLE. Rats were made chronically epileptic by a period of continuous electrical stimulation of the hippocampus, which establishes an acute condition of self-sustained limbic status epilepticus (SSLSE). This period of SSLSE is followed by a development of chronic recurrent spontaneous limbic seizures that are associated with chronic neuropathological changes reminiscent of those encountered in human TLE. Under visual control, whole cell patch-clamp recordings of interneurons and pyramidal cells were obtained in area CA1 of slices taken from adult, chronically epileptic post-SSLSE rats. Neurons were activated by means of electrodes positioned in stratum radiatum. Intrinsic membrane properties, including resting membrane potential, action potential (AP) threshold, AP half-height width, and membrane impedance, were unchanged in interneurons from chronically epileptic (post-SSLSE) tissue compared with control tissue. Single stimuli delivered to stratum radiatum evoked depolarizing excitatory postsynaptic potentials and APs in interneurons, whereas paired-pulse stimulation evoked facilitation of the postsynaptic current (PSC) in both control and post-SSLSE tissue. No differences between interneurons in control versus post-SSLSE tissue could be found with respect to the mean stimulus intensity or mean stimulus duration needed to evoke an AP. A multiple linear regression analysis over a range of stimulus intensities demonstrated that a greater number of APs could be evoked in interneurons in post-SSLSE tissue compared with control tissue. Spontaneous PSCs were observed in area CA1 interneurons in both control and post-SSLSE tissue and were markedly attenuated by glutamatergic antagonists. In conclusion, our data suggest that stimulus-evoked and spontaneous excitatory synaptic input to area CA1 interneurons remains functional in an animal model of chronic temporal lobe epilepsy. These findings suggest, therefore, that the apparent decrease of polysynaptic inhibitory PSPs in CA1 pyramidal cells in epileptic tissue is not due to a deficit in excitatory transmission from Schaffer collaterals to interneurons in stratum radiatum and straum oriens.

Animals↗
PubMed2006

Contribution of AMPA and NMDA receptors to early and late phases of LTP in hippocampal slices.

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and N-methyl-D-aspartate (NMDA) receptor mediated responses were investigated in rat hippocampal slices under 4h of long-term potentiation (LTP) expression. A modified medium containing the NMDA receptor antagonist AP5 and low concentration of Mg(2+) was used to monitor isolated AMPA responses. NMDA components were determined from composite excitatory postsynaptic potentials (EPSPs) under brief (15-20 min) wash-out of AP5. LTP was induced in a medium with low concentration of AP5, resulting in an about two-fold larger increase of the AMPA component than of the NMDA component at both 1h and 4h after induction. Similar results were obtained if LTP was induced in "normal Mg(2+)" and the NMDA components were assessed at the end of experiment, from either composite or isolated NMDA EPSPs, with or without blockade of GABAergic inhibition. It is generally believed that LTP undergoes biochemical and/or structural conversions during the first few hours. Our study, however, shows constant expression of LTP, at least in terms of AMPA versus NMDA components, during this time. The data support the notion that LTP initiates as a predominant amplification of AMPA receptors and remains so for at least 4h.

Animals↗
PubMed2001

Tonically active protein kinase A regulates neurotransmitter release at the squid giant synapse.

1. Electrophysiological and microinjection methods were used to examine the role of cyclic AMP-dependent protein kinase A (PKA) in regulating transmitter release at the squid giant synapse. 2. Excitatory postsynaptic potentials (EPSPs) evoked by presynaptic action potentials were not affected by presynaptic injection of an exogenous active catalytic subunit of mammalian PKA. 3. In contrast, presynaptic injection of PKI-amide, a peptide that inhibits PKA with high potency and specificity, led to a reversible inhibition of EPSPs. 4. Injection of several other peptides that serve as substrates for PKA also reversibly inhibited neurotransmitter release. The ability of these peptides to inhibit release was correlated with their ability to serve as PKA substrates, suggesting that these peptides act by competing with endogenous substrates for phosphorylation by active endogenous PKA. 5. We suggest that the phosphorylation of PKA substrates is maintained at a relatively high state under basal conditions and that this tonic activity of PKA is to a large degree required for evoked neurotransmitter release at the squid giant presynaptic terminal.

Action Potentials↗
PubMed1992

Enhancement of postsynaptic responsiveness during long-term potentiation of mossy fiber synapses in guinea pig hippocampus.

The primary site responsible for the long-lasting enhancement of synaptic transmission during long-term potentiation (LTP) was examined by quantal analysis of excitatory postsynaptic potentials in thin sections of the guinea pig hippocampus. With induction of LTP in mossy fiber synapses, estimated values of quantal amplitude (q) and Pascal parameters p and r were increased significantly. No increases in quantal content (m) were detected. The magnitude of increases in q was almost equal to that of LTP. These results indicate that LTP in mossy fiber synapses results from increases in responsiveness of postsynaptic neurons.

Afferent Pathways↗
PubMed2006

Persistent alterations to enteric neural signaling in the guinea pig colon following the resolution of colitis.

Functional changes induced by inflammation persist following recovery from the inflammatory response, but the mechanisms underlying these changes are not well understood. Our aim was to investigate whether the excitability and synaptic properties of submucosal neurons remained altered 8 wk post-trinitrobenzene sulfonic acid (TNBS) treatment and to determine whether these changes were accompanied by alterations in secretory function in submucosal preparations voltage clamped in Ussing chambers. Mucosal serotonin (5-HT) release measurements and 5-HT reuptake transporter (SERT) immunohistochemistry were also performed. Eight weeks after TNBS treatment, colonic inflammation resolved, as assessed macroscopically and by myeloperoxidase assay. However, fast excitatory postsynaptic potential (fEPSP) amplitude was significantly increased in submucosal S neurons from previously inflamed colons relative to those in control tissue. In addition, fEPSPs from previously inflamed colons had a hexamethonium-insensitive component that was not evident in age-matched controls. AH neurons were hyperexcitable, had shorter action potential durations, and decreased afterhyperpolarization 8 wk following TNBS adminstration. Neuronally mediated colonic secretory function was significantly reduced after TNBS treatment, although epithelial cell signaling, as measured by responsiveness to both forskolin and bethanecol in the presence of tetrodotoxin, was comparable with control tissue. 5-HT levels and SERT immunoreactivity were comparable to controls 8 wk after the induction of inflammation, but there was an increase in glucagon-like peptide 2-immunoreactive L cells. In conclusion, sustained alterations in enteric neural signaling occur following the resolution of colitis, which are accompanied by functional changes in the absence of active inflammation.

Action Potentials↗
PubMed1999

Group I mGluR agonist DHPG facilitates the induction of LTP in rat prelimbic cortex in vitro.

Long-term potentiation (LTP) of synaptic transmission is a favored neural model for learning and memory. In isolated slices of rat prelimbic cortex, glutamatergic activation of metabotropic receptors (mGluRs) is required for the production of LTP at synapses on layer V neurons. Group I mGluRs are found in neocortex, and in prelimbic cortex they have been located on layer V neurons. We have now investigated whether application of the selective group I mGluR agonist, (S)-3,5-dihydroxyphenylglycine (DHPG) facilitates the induction of LTP. We recorded field potentials in layer V in response to test shocks applied to layer II and measured the population spike peak amplitude and slope. Intracellular recording was used to examine the correspondence between excitatory postsynaptic potentials (EPSPs) and action potentials with components of the field potential, and to further investigate the action of DHPG. Repetitive bursts of stimulation at theta frequencies (TBS) did not consistently alter the magnitude or slope of the population spike (mean response 105+/-4%, mean+/-SE of control at 30 min after TBS ended, n = 9 slices, no significant difference). When DHPG was added to the bathing medium for 10 min during continued test stimulation, the slope and amplitude of the population spike were significantly reduced, but 30 min after wash out of the DHPG, they recovered (mean response 89+/-10% of control, n = 6 slices, no significant difference). However, when TBS was administered in conjunction with bath application of DHPG, LTP of the population spike was induced (mean response 147+/-12% of control at 30 min after TBS ended, P = 0.004, paired t-test, n = 9 slices). We conclude that co-application of DHPG with TBS facilitates the induction of LTP of the population spike, which supports a role for group I mGluRs in the activity-dependent induction of LTP in the prelimbic cortex.

Animals↗
PubMed1999

Nonlinear frequency-dependent synchronization in the developing hippocampus.

Synchronous population activity is present both in normal and pathological conditions such as epilepsy. In the immature hippocampus, synchronous bursting is an electrophysiological conspicuous event. These bursts, known as giant depolarizing potentials (GDPs), are generated by the synchronized activation of interneurons and pyramidal cells via GABAA, N-methyl-D-aspartate, and AMPA receptors. Nevertheless the mechanism leading to this synchronization is still controversial. We have investigated the conditions under which synchronization arises in developing hippocampal networks. By means of simultaneous intracellular recordings, we show that GDPs result from local cooperation of active cells within an integration period prior to their onset. During this time interval, an increase in the number of excitatory postsynaptic potentials (EPSPs) takes place building up full synchronization between cells. These EPSPs are correlated with individual action potentials simultaneously occurring in neighboring cells. We have used EPSP frequency as an indicator of the neuronal activity underlying GDP generation. By comparing EPSP frequency with the occurrence of synchronized GDPs between CA3 and the fascia dentata (FD), we found that GDPs are fired in an all-or-none manner, which is characterized by a specific threshold of EPSP frequency from which synchronous GDPs emerge. In FD, the EPSP frequency-threshold for GDP onset is 17 Hz. GDPs are triggered similarly in CA3 by appropriate periodic stimulation of mossy fibers. The frequency threshold for CA3 GDP onset is 12 Hz. These findings clarify the local mechanism of synchronization underlying bursting in the developing hippocampus, indicating that GDPs are fired when background levels of EPSPs or action potentials have built up full synchronization by firing at specific frequencies (>12 Hz). Our results also demonstrate that spontaneous EPSPs and action potentials are important for the initiation of synchronous bursts in the developing hippocampus.

Action Potentials↗
PubMed2000

Electrical properties and synaptic potentials of rabbit pancreatic neurons.

Pancreatic ganglia receive innervation from a wide variety of extrinsic nerves and supply the predominant innervation to pancreatic acini, islets, and ducts. This study used intracellular recordings to investigate the electrical properties and synaptic potentials of rabbit pancreatic neurons. Neurons had a mean resting membrane potential of -54+/-0.4 mV and generated action potentials with a mean overshoot of 10+/-0.4 mV and a mean after-spike hyperpolarization (ASH) of 11+/-0.5 mV with duration of 210+/-19 ms. Action potentials exhibited a high threshold (-15+/-1 mV) for intracellular stimulation and a phasic firing pattern was observed in response to prolonged depolarizing currents. Stimulation of attached nerve bundles evoked multiple fast excitatory postsynaptic potentials (fEPSPs) which were abolished by hexamethonium in 75% of neurons, while a non-cholinergic fEPSP was observed in 25% of the neurons. Repetitive stimulation (3-30 Hz) evoked muscarinic slow EPSPs with a mean amplitude of 8+/-2 mV and duration of 5+/-1 s in a small subset (21%) of neurons. Exogenous muscarine evoked a mean slow depolarization of 10+/-1 mV amplitude in 22% of neurons tested. Following repetitive nerve stimulation non-cholinergic late, slow EPSPs with a mean amplitude of 4.3+/-0.4 mV were recorded in 32% of neurons. Nicotinic transmission was subject to inhibition mediated by presynaptic muscarinic receptors at low (0.5 Hz) stimulus frequencies in 80% of neurons. At higher frequencies (> or =1 Hz), either facilitation or depression of nicotinic transmission was observed depending on the ganglion studied. A population (9%) of neurons exhibited spontaneous, low-amplitude pacemaker-like potentials. Spontaneous fEPSPs and action potentials were also observed and these occasionally occurred in rhythmically timed bursts. Thus, distinct subpopulations of pancreatic neurons could be identified on the basis of both their intrinsic electrical properties and the receptors mediating and/or modulating synaptic transmission. These neurons function as critical sites of integration for synaptic input from extrinsic pancreatic nerves and thereby determine the postganglionic firing patterns presented to the pancreatic exocrine and endocrine secretory cells.

Animals↗
PubMed1992

A highly selective kappa-opioid receptor agonist, CI-977, reduces excitatory synaptic potentials in the rat locus coeruleus in vitro.

Intracellular recordings were made from neurons in a rat locus coeruleus slice preparation in vitro. A postsynaptic potential was evoked by electrical stimulation of afferents to the neurons. CI-977 ([5R-(5a,7a,8b)]-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec -8-yl[-4-benzofuranacetamide monohydrochloride) caused a depression of the evoked postsynaptic potential on locus coeruleus neurons. This action was reversed on washout. Bremazocine had a similar action on less than 50% of locus coeruleus neurons. Concentrations of CI-977 which depressed the postsynaptic potential did not affect either passive membrane conductance or a voltage-sensitive potassium current resembling IA. The depression of the excitatory postsynaptic potential caused by CI-977 remained in the presence of either 30 microM bicuculline and picrotoxin or when potassium acetate-filled recording electrodes were used. Using potassium chloride-filled recording electrodes and in the presence of 30 microM 6-cyano-2,3-dihydro-7-nitroquinoxaline-2,3-dione and either 30 microM DL-2-amino-5-phosphonovaleric acid or 500 microM kynurenic acid, CI-977 had no effect on the postsynaptic potential. The effects of CI-977 were reversed by 30-100 nM naloxone and 1-10 nM norbinaltorphimine but not by 1-10 nM naloxone. The hyperpolarizing response to the mu-opioid receptor-selective agonist D-Ala2,Nme Phe4,Gly-ol5 (DAGOL) was blocked by 1-10 nM naloxone but not by 1-100 nM norbinaltorphimine. The hyperpolarizing response to DAGOL was not affected by high doses of CI-977.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acids↗
PubMed2001

Epileptiform activity and EPSP-spike potentiation induced in rat hippocampal CA1 slices by repeated high-K(+): involvement of ionotropic glutamate receptors and Ca(2+)/calmodulin-dependent protein kinase II.

We have previously demonstrated that repeated brief increases in extracellular K(+) (K(+)(o)) induce a hyperexcitability in CA1 pyramidal cells that persists for a long time after the final application of K(+) [Neurosci. Lett. 223 (1997) 177; Epilepsy Research (2000) 75]. This epileptiform activity, which was associated with a lasting excitatory postsynaptic potential (EPSP)-spike potentiation, presented some of the characteristic features of traditional in vivo kindling. We have also found that Ca(2+) influx through L-type voltage-sensitive Ca(2+) channels is essential for the development of both in vitro kindling and EPSP-spike potentiation. The aims of this study were to investigate the involvement of ionotropic glutamate receptors, especially those of the NMDA subtype, and the requirement for Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in these phenomena. Field EPSPs with presynaptic fibre volleys from the stratum radiatum, and population spikes from the stratum pyramidale, were recorded in the CA1 area of rat hippocampal slices in response to electrical stimulation of the Schaffer collateral/commissural fibres. Repeated (three episodes) brief (30 s) increases in extracellular K(+) induced a sustained decrease in the threshold for development of evoked epileptiform discharges (i.e. an in vitro kindling-like state) and a lasting potentiation of the EPSP-spike transfer in CA1 pyramidal neurons (EPSP-spike potentiation). The selective antagonist of NMDA receptors, APV (50 microM), blocked the EPSP-spike potentiation, depressed the induction phase of the in vitro kindling-like state, and blocked the maintenance phase of this state. In contrast to APV, the blockade of AMPA/kainate receptors by CNQX (10 microM) had no effect. Like APV, KN62 (3 microM), a selective membrane permeable inhibitor of CaMKII, blocked the EPSP-spike potentiation and the maintenance phase of the in vitro kindling-like state. Our previous and present results therefore demonstrate that Ca(2+) influxes through L-type voltage-dependent-and NMDA receptor-dependent-Ca(2+) channels contribute differentially to the development of an in vitro kindling-like state, and both induce EPSP-spike potentiation in CA1 hippocampal pyramidal cells in response to repeated brief increases in K(+)(o). It is suggested that these effects of intracellular Ca(2+) on the maintenance phase of the in vitro kindling-like state and EPSP-spike potentiation are mediated by CaMKII-dependent mechanisms.

Animals↗