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At least 1,585 records · Page 88Linked to original sources
PubMed1989

Synaptic transmission at the Schaffer-CA1 synapse is blocked by 6,7-dinitro-quinoxaline-2,3-dione. An in vivo brain dialysis study in the rat.

6,7-Dinitro-quinoxaline-2,3-dione (DNQX, FG 9041), a new non-N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, has been reported to block non-NMDA receptor-mediated excitatory amino acidic responses in cultured neurons. We have perfused this compound in vivo through a dialysis fiber placed in the CA1 regions of anesthetized rats to test its effects on CA1 field-evoked potentials. Perfusions of 25-100 microM DNQX completely abolished field excitatory postsynaptic potentials (EPSP) and orthodromic population spikes (PS). This effect was dose-dependent and was reversed after washing with fresh Krebs-Ringer-bicarbonate. Antidromic population spikes and fiber volley potentials were unaffected by perfusions of DNQX up to 100 microM. On the contrary, perfusion of 50 microM D-2-amino-5-phosphonovalerate, a specific NMDA receptor antagonist, left unchanged both field EPSP and orthodromic PS. Results demonstrate that low-frequency transmission at the Schaffer collaterals-CA1 synapse is mediated by non-NMDA glutamate receptors.

Action Potentials↗
PubMed1996

Interleukin-1 beta (IL-1 beta) and tumour necrosis factor (TNF) inhibit long-term potentiation in the rat dentate gyrus in vitro.

The effects of the cytokine, interleukin-1 beta (IL-1 beta), and its receptor antagonist IL-1ra, were studied on long-term potentiation in the dentate gyrus of rat hippocampal slices. Field excitatory postsynaptic potentials were recorded extracellularly in the molecular region of the dentate gyrus in response to stimulation of the medial perforant path. Low frequency synaptic transmission was unaffected by IL-1 beta (1 ng/ml), but pre-treatment with IL-1 beta completely blocked induction of long-term potentiation. Co-application of IL-1 beta and IL-1ra (100 ng/ml) attenuated the inhibitory effect of IL-1 beta. In parallel with these findings, we demonstrate that IL-1 beta also inhibited 45Ca influx into the slices. The inhibitory effect of IL-1 beta on induction was mimicked by tumour necrosis factor (TNF; 4.5 ng/ml) and lipopolysaccharide (LPS; 10 micrograms/ml). These results indicate a modulatory role for cytokines in hippocampus and suggest that the inhibitory effect of IL-1 beta on long-term potentiation may relate to its inhibitory effect on calcium channel activity.

Animals↗
PubMed1996

Spatial and temporal analysis of evoked neural activity in optical recordings from American cockroach antennal lobes.

The spatio-temporal patterns of neural activity evoked by electrical stimuli to the antennal nerve (AN) in male cockroach antennal lobes (ALs) in vivo were analyzed by optical imaging using a voltage-sensitive dye. The response pattern was initially a depolarization on the AN and subsequently a depolarization followed by a hyperpolarization on the whole area of macroglomerulus (MG) and a part of ordinary glomerulus (OG). It was suggested by the pharmacological results that the depolarizing responses on the AL consist of both a presynaptic response, representing synchronous compound action potentials from the AN, and a postsynaptic response, representing synchronous compound excitatory postsynaptic potentials and action potentials from neurites of AL neurons, and that the inhibitory responses of GABAergic local interneurons in the AN are different in time course from that in the AL.

Action Potentials↗
PubMed1994

Involvement of N- and non-N-type calcium channels in synaptic transmission at corticostriatal synapses.

Calcium channels participate in the events linking axon terminal depolarization to neurotransmitter secretion. We wished to evaluate the role of N-type and non-N-type calcium channels in glutamatergic transmission at corticostriatal synapses, since this is a well defined excitatory synapse. In addition, these synapses are subject to a variety of forms of presynaptic modulation, some of which may involve alterations in calcium channel function. Application of the selective N-type channel blocker omega-conotoxin GVIA produced an irreversible depression of excitatory synaptic transmission in rat neostriatal slices shown by a decrease of approximately 50% in the amplitude of the synaptically driven population spike during field potential recording and a similar decrease in the amplitude of excitatory postsynaptic potentials during whole-cell recording. The component of transmission which was resistant to omega-conotoxin GVIA was blocked by omega-conotoxin MVIIC. omega-Agatoxin IVA had little effect on transmission. Activation of a presynaptic metabotropic glutamate receptor depressed transmission to a similar extent before and after omega-conotoxin GVIA treatment. Likewise, protein kinase C-activating phorbol esters potentiated transmission to the same extent before and after omega-conotoxin GVIA treatment. N-type calcium channels appear to be crucial for a component of excitation-secretion coupling at corticostriatal synapses. A component of transmission involves non-N-, non-L-type high-voltage-activated calcium channels. The effects of presynaptic metabotropic receptors and protein kinase C activation cannot be accounted for solely by alterations in the N-type channel function.

Animals↗
PubMed1993

Long-term enhancement of EPSP and NMDA receptor-mediated synaptic transmission in the amygdala.

An in vitro slice preparation of rat amygdala was used to study the long-term modifications of synaptic efficacy following high-frequency stimulation of the ventral endopyriform nucleus. Delivery of brief tetani to the afferent fibers led to a long-term potentiation (LTP) of the amplitude and the initial slope of excitatory postsynaptic potential (EPSP). Pretreatment the slices with DL-2-amino-5-phosphonovaleate (DL-APV, 50 microM) blocked the induction of LTP, indicating that N-methyl-D-aspartate (NMDA) receptor activation is required for induction. NMDA receptor-mediated component of synaptic response (EPSPNMDA) was isolated by application of a solution containing 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX, 10 microM) and bicuculline (20 microM). Tetanic stimulation led to a lasting potentiation of the EPSPNMDA. These results suggest that brief repetitive stimulation of afferent pathway produces forms of LTP that share many properties of LTP seen in the CA1 region of the hippocampus.

2-Amino-5-phosphonovalerate↗
PubMed2005

Abnormal synaptic plasticity in the Ts1Cje segmental trisomy 16 mouse model of Down syndrome.

Due to the homology between human chromosome 21 and mouse chromosome 16, trisomy 16 mice are considered animal models of Down syndrome (DS). Abnormal hippocampal synaptic plasticity and behavior have been reported in the segmental trisomy 16 Ts65Dn mouse. In the Ts1Cje DS mouse model, which has a shorter triplicated chromosomal segment than Ts65Dn, more subtle hippocampal behavioral deficits have been reported. In this study, we investigated CA1 hippocampal synaptic plasticity, long-term potentiation (LTP) and depression (LTD) in the Ts1Cje mouse. Field excitatory postsynaptic potentials (fEPSPs) were recorded from the CA1 area of in vitro hippocampal slices from the Ts1Cje mouse and diploid controls, LTP was induced by a single tetanizing train pulse (1 s) at 100 Hz and LTD by a 900-pulse train at 1 Hz. We report for the first time that compared to diploid controls, the hippocampus from the Ts1Cje mouse had a smaller LTP and an increased LTD. The changes are less dramatic than had been reported previously for the Ts65Dn mouse. Furthermore, in the Ts1Cje mouse trains of pulses at both 20 Hz and 100 Hz produced a decrease in the evoked fEPSPs over the length of the train in comparison to diploid fEPSPs. These findings suggest that genes from Ts1Cje chromosome, including GIRK2 potassium channel, contribute to abnormal short- and long-term plasticity.

Action Potentials↗
PubMed1999

In vivo induction of striatal long-term potentiation by low-frequency stimulation of the cerebral cortex.

Both long-term depression and long-term potentiation have been described at corticostriatal synapses. These long-lasting changes in synaptic strength were classically induced by high-frequency (100 Hz) electrical stimulations of cortical afferents. The purpose of the present study was to test the ability of corticostriatal connections to express use-dependent modifications after cortical stimulation applied at the frequency of synchronization of corticostriatal inputs observed in our in vivo preparation, i.e. the barbiturate-anesthetized rat. For this study we used an identified monosynaptic corticostriatal pathway, between the orofacial motor cortex and its target region in the striatum. Intracellular recording of striatal output neurons showed spontaneous large-amplitude oscillation-like depolarizations exhibiting a strong periodicity with a narrow frequency band at 5 Hz. Using the focal electroencephalogram of the cortical region projecting to the recorded cells, we found that membrane potential oscillations in striatal neurons were in phase with episodes of spontaneous cortical spindle waves. To determine directly the pattern of activity of corticostriatal neurons, we performed intracellular recordings of electrophysiologically identified corticostriatal neurons simultaneously with the corresponding surface electroencephalogram. We found that corticostriatal cells (n = 7) exhibited periods of spontaneous 5-Hz discharges in phase with the cortical spindle waves. Therefore, we have tested the effect of repetitive cortical stimulations at this low frequency (5 Hz, 500-1000 pulses) on the corticostriatal synaptic efficacy. In 62% of cases (eight of 13 neurons tested), this conditioning was able to produce long-term potentiation in the corticostriatal synaptic efficacy. The mean increase of excitatory postsynaptic potential amplitude ranged from 13.3% to 172% (mean = 67.3%, n = 8). These results provide additional support for physiological long-term potentiation at corticostriatal connections. Furthermore, this study demonstrates that corticostriatal long-term potentiation can be induced by synchronization at low frequency of cortical afferents. Our data support the concept that the striatal output neuron may operate as a coincidence detector of converging cortical information.

Animals↗
PubMed1996

Short-term synaptic enhancement and long-term potentiation in neocortex.

Repetitive stimuli reliably induce long-term potentiation (LTP) of synapses in the upper layers of the granular somatosensory cortex but not the agranular motor cortex of rats. Herein we examine, in these same cortical areas, short-term changes in synaptic strength that occur during the LTP induction period. theta-Burst stimulation produced a strong short-term enhancement of synapses in the granular area but only weak enhancement in the agranular area. The magnitude of enhancement during stimulation was strongly correlated with the magnitude of LTP subsequently expressed. Short-term enhancement was abolished by an antagonist of N-methyl-D-aspartate (NMDA) receptors but remained in the presence of a non-NMDA receptor antagonist. Inhibitory postsynaptic potentials of the granular and agranular areas displayed similar frequency sensitivity, but the frequency sensitivity of NMDA receptor-dependent excitatory postsynaptic potentials differed significantly between areas. We propose that pathway-specific differences in short-term enhancement are due to variations in the frequency dependence of NMDA currents; different capacities for short-term enhancement may explain why repetitive stimulation more readily induces LTP in the somatosensory cortex than in the motor cortex.

2-Amino-5-phosphonovalerate↗
PubMed1997

Noradrenaline modulates glutamate-mediated neurotransmission in the rat basolateral amygdala in vitro.

The entorhinal cortex and the amygdala are interconnected structures of the limbic system in which paroxysmal activity occurs during temporal lobe epilepsy. Conflicting evidence shows that noradrenaline (i) inhibits the spreading to other parts of the limbic system of paroxysmal activity generated in the amygdala or the entorhinal cortex, but also (ii) increases glutamatergic transmission in the basolateral amygdala. Given our previous work on the inhibitory effect of noradrenaline on entorhinal cortex neurons, we developed an in vitro slice preparation to study the synaptic transmission in the basolateral amygdala and its modulation by noradrenaline. Noradrenaline reduced the fast excitatory postsynaptic potential (EPSP) by approximately 40% at 100 microM and the slow EPSP by approximately 50% at 50 microM. A similar effect was obtained with the alpha2-agonist UK 14304 at 100 and 50 microM respectively. In contrast, the beta-agonist isoproterenol increased the fast EPSP by approximately 40% at 100 microM and the slow EPSP by approximately 20% at 50 microM. Accordingly, the effect of noradrenaline on the EPSPs was blocked by the alpha2-antagonist yohimbine (10 microM) but not by the alpha1-antagonist prazosine (10 microM) and the beta-antagonist propranolol (10 microM). Noradrenaline (50-100 microM) was ineffective on most (14/16) of the isolated inhibitory postsynaptic potentials (IPSPs). These experiments provide evidence that noradrenaline inhibits the excitatory synaptic response of basolateral amygdala neurons. A pharmacological analysis revealed that the noradrenergic modulation of the excitatory transmission in the basolateral amygdala can be dissected into a predominant alpha2-adrenoreceptor-mediated inhibition and a beta-adrenoreceptor-mediated excitation.

Amygdala↗
PubMed1991

Intracellular recordings from gallbladder ganglia of opossums.

Postganglionic parasympathetic neurons of the opossum gallbladder were studied using morphological and intracellular electrophysiological recording techniques. On average there were 17 ganglia/cm2 with 8 neurons/ganglion arranged as loosely or densely packed clusters. Intracellular injection of horseradish peroxidase identified two types of neurons. Most of the neurons (approximately 80%) had a single long process that extended beyond the ganglion border with few or no short additional neurites. The other type was multipolar, having several processes that did not appear to extend beyond the ganglion border. Gallbladder neurons had passive and active electrical properties similar to other parasympathetic ganglion cells. Most of neurons studied (71%) responded to intracellular injection of suprathreshold depolarizing current with a short burst of action potentials. The remaining neurons (29%) responded with only an initial action potential. Seventy percent of the neurons tested received nicotinic fast excitatory postsynaptic potentials (EPSPs). Nineteen percent of these neurons also exhibited a slow depolarizing response following repetitive orthodromic nerve stimulation. Cholecystokinin octapeptide sulfate (CCK-8, 0.1-500 nM) had no effect on resting membrane potential or membrane input resistance. However, CCK-8 increased the amplitude of fast EPSPs evoked by orthodromic nerve stimulation by facilitating release of acetylcholine because CCK-8 had no effect on the postsynaptic response to exogenously applied acetylcholine. These data suggest that the ganglionated plexus of the gallbladder may mediate some of the observed effects of CCK-8 on gallbladder motility.

Acetylcholinesterase↗
PubMed1992

Endogenous adenosine contributes to hypoxic synaptic depression in hippocampus from young and aged rats.

1. Extracellular field potentials were recorded to study the role of endogenous adenosine during hypoxia in area CA1 of rat hippocampal slices. 2. Hypoxic conditions, induced by 15 min exposure to 95% N2-5% CO2 at 32 degrees C and in high-glucose incubation medium, produced a rapid and reversible depression of evoked synaptic potentials. 3. In slices from young Sprague-Dawley rats, the hypoxia-induced synaptic depression was reduced in a concentration-dependent manner by the adenosine antagonist 8-cyclopentyltheophylline (8-CPT; 100 nM-2.0 microM). 4. Recovery of synaptic potentials after hypoxia was complete under each experimental condition. 5. Extended periods of hypoxia lasting 30 min likewise produced a rapid and near total suppression of the evoked synaptic potentials. In the presence of 8-CPT, both the population excitatory postsynaptic potential (EPSP) slope and population spike amplitude were significantly preserved throughout the hypoxic episode. 6. Neither the onset rate nor the degree of the hypoxia-induced synaptic depression were significantly different in slices from young, adult, or aged Fischer 344 rats. Reduction of the hypoxia-induced response depression by 8-CPT was also similar in all age groups. 7. These findings have further characterized the important involvement of endogenous adenosine in the potentially neuroprotective synaptic depression observed in hippocampal slices from young and aged rats during hypoxia.

Adenosine↗
PubMed1994

Electrophysiology of globus pallidus neurons in vitro.

1. We investigated the electrical properties of globus pallidus neurons intracellularly using brain slices from adult guinea pigs. Three types of neurons were identified according to their intrinsic electrophysiological properties. 2. Type I neurons (59%) were silent at the resting membrane level (-65 +/- 10 mV, mean +/- SD) and generated a burst of spikes, with strong accommodation, to depolarizing current injection. Calcium-dependent low-frequency (1-8 Hz) membrane oscillations were often elicited by membrane depolarization (-53 +/- 8 mV). A low-threshold calcium conductance and an A-current were also identified. The mean input resistance of this neuronal type was 70 +/- 22 M omega. 3. Type II neurons (37%) fired spontaneously at the resting membrane level (-59 +/- 9 mV). Their repetitive firing (< or = 200 Hz) was very sensitive to the amplitude of injected current and showed weak accommodation. Sodium-dependent high-frequency (20-100 Hz) subthreshold membrane oscillations were often elicited by membrane depolarization. This neuronal type demonstrated a low-threshold calcium spike and had the highest input resistance (134 +/- 62 M omega) of the three neuron types. 4. Type III neurons (4%) did not fire spontaneously at the resting membrane level (-73 +/- 5 mV). Their action potentials were characterized by a long duration (2.3 +/- 0.6 ms). Repetitive firing elicited by depolarizing current injection showed weak or no accommodation. This neuronal type had an A-current and showed the lowest input resistance (52 +/- 35 M omega) of the three neuron types. 5. Stimulation of the caudoputamen evoked inhibitory postsynaptic potentials (IPSPs) in Type I and II neurons. In Type II neurons the IPSPs were usually followed by rebound firing. Excitatory postsynaptic potentials and antidromic responses were also elicited in some Type I and II neurons. The estimated conduction velocity of the striopallidal projection was < 1 m/s (Type I neurons, 0.49 +/- 0.37 m/s; Type II neurons, 0.33 +/- 0.13 m/s).

Animals↗
PubMed1985

Synaptic plasticity in the molluscan peripheral nervous system: physiology and role for peptides.

The plasticity of a synapse in the molluscan peripheral nervous system was examined under a variety of experimental, physiological, and pharmacological conditions. These studies employed the isolated salivary glands and attached buccal ganglia of the freshwater snail Helisoma. Action potentials evoked in buccal neuron 4 normally evoke a large excitatory postsynaptic potential (EPSP) which drives an action potential in gland secretory cells. In order to measure modulation of the EPSP, action potential generation in gland cells was prevented by bathing the preparation in low calcium, high magnesium salines. The relationship between the gland EPSP amplitude and specific physiological properties of neuron 4 was analyzed. In common with some central molluscan synapses, the EPSP was found to be strongly influenced by the membrane potential of neuron 4. Specifically, its amplitude was reduced by hyperpolarization of the neuron 4 soma. The relationship between EPSP amplitude and somatic potential of neuron 4 was linear in the range from resting potential (-47 +/- 6mV) to -100 mV. Furthermore, the EPSP amplitude was directly proportional to the action potential half-width of neuron 4. In order to evaluate the possible physiological role of this action potential/EPSP relationship, we examined whether gland EPSPs are modulated during the spike broadening that occurs in both spontaneous burst activity and imposed impulse trains. The preceding action potential/EPSP relationship was maintained under both of these conditions, i.e., EPSP magnitude increased as spikes broadened during bursts or trains. The peptidergic modulation of neuroglandular transmission was also examined. The molluscan peptide SCPB was found to depolarize neuron 4 and an increase in EPSP amplitude was concomitantly observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Action Potentials↗
PubMed1996

Comparison of peripheral Ia and corticomotoneuronal composite EPSPs in human motoneurons.

The effects of excitatory inputs arising from Ia afferent and corticomotoneuronal volleys on repetitively firing flexor carpi radialis (FCR) motoneurons were compared in normal human subjects. Peripheral (Ia) volleys were produced by transcutaneous electrical stimulation of the median nerve and by mechanical taps to the FCR tendon. Transcranial magnetic stimulation (TMS) was used to activate the corticomotoneuronal pathway. The duration of the excitatory response peaks measured from peri-stimulus time histograms (PSTHs) and the time course of the response trajectories were both taken to reflect the shapes of the underlying composite excitatory postsynaptic potentials (EPSP)s acting upon that motoneuron. The duration of excitatory response peaks for the H-reflex and the first sub-peak (SP1) of the motor unit's response to TMS were similar and were typically less than those arising from tendon taps. The response trajectories, which measure the excitability of the motoneuron during different phases of the afterhyperpolarization, overlapped for H-reflex and SP1 responses, but were different for tendon tap inputs. Our results indicate that the SP1 response of a motoneuron to TMS input and its response to near-synchronous Ia afferent activation are mediated by composite EPSPs with similar rise times. We suggest that a similar spatial distribution of synaptic boutons for both Ia and corticomotoneuronal input to motoneurons innervating FCR is likely.

Adult↗
PubMed1997

Canal-specific excitation and inhibition of frog second-order vestibular neurons.

Second-order vestibular neurons (secondary VNs) were identified in the in vitro frog brain by their monosynaptic excitation following electrical stimulation of the ipsilateral VIIIth nerve. Ipsilateral disynaptic inhibitory postsynaptic potentials were revealed by bath application of the glycine antagonist strychnine or of the gamma-aminobutyric acid-A (GABA(A)) antagonist bicuculline. Ipsilateral disynaptic excitatory postsynaptic potentials (EPSPs) were analyzed as well. The functional organization of convergent monosynaptic and disynaptic excitatory and inhibitory inputs onto secondary VNs was studied by separate electrical stimulation of individual semicircular canal nerves on the ipsilateral side. Most secondary VNs (88%) received a monosynaptic EPSP exclusively from one of the three semicircular canal nerves; fewer secondary VNs (10%) were monosynaptically excited from two semicircular canal nerves; and even fewer secondary VNs (2%) were monosynaptically excited from each of the three semicircular canal nerves. Disynaptic EPSPs were present in the majority of secondary VNs (68%) and originated from the same (homonymous) semicircular canal nerve that activated a monosynaptic EPSP in a given neuron (22%), from one or both of the other two (heteronymous) canal nerves (18%), or from all three canal nerves (28%). Homonymous activation of disynaptic EPSPs prevailed (74%) among those secondary VNs that exhibited disynaptic EPSPs. Disynaptic inhibitory postsynaptic potentials (IPSPs) were mediated in 90% of the tested secondary VNs by glycine, in 76% by GABA, and in 62% by GABA as well as by glycine. These IPSPs were activated almost exclusively from the same semicircular canal nerve that evoked the monosynaptic EPSP in a given secondary VN. Our results demonstrate a canal-specific, modular organization of vestibular nerve afferent fiber inputs onto secondary VNs that consists of a monosynaptic excitation from one semicircular canal nerve followed by disynaptic excitatory and inhibitory inputs originating from the homonymous canal nerve. Excitatory and inhibitory second-order (secondary) vestibular interneurons are envisaged to form side loops that mediate spatially similar but dynamically different signals to secondary vestibular projection neurons. These feedforward side loops are suited to adjust the dynamic response properties of secondary vestibular projection neurons by facilitating or disfacilitating phasic and tonic input components.

Animals↗
PubMed2004

Synaptically recruited apical currents are required to initiate axonal and apical spikes in hippocampal pyramidal cells: modulation by inhibition.

Dendritic voltage-dependent currents and inhibition modulate the information flow between synaptic and decision areas. Subthreshold and spike currents are sequentially recruited by synaptic potentials in the apical shaft of pyramidal cells, which may also decide cell output. We studied the global role of proximal apical recruited currents on cell output in vitro and in the anesthetized rat after local blockade of Na+ currents in the axon initial segment (AIS) or the proximal apical shaft and their modulation by inhibition. Microejection of TTX, field potentials, and intrasomatic and intradendritic recordings were employed. Dendritic population spikes (PSs) were much smaller in vitro, but the gross relations between synaptic and active currents are similar to in vivo. Activation of Schaffer collaterals triggered PSs and action potentials (APs) in the apical shaft that fully propagated to the axon. However, the specific blockade of proximal Na+ currents avoided cell firing, although antidromic PSs and APs readily invaded somata. The somatic depolarization of subthreshold excitatory postsynaptic potentials (EPSPs) also decreased to about 50%. These results were not due to decreased excitatory input by TTX. However, when GABA(A) inhibition was locally removed, Schaffer synaptic currents skipped the proximal dendrite and fired somatic PSs, although initiated at the AIS. It is concluded that apical currents recruited en passant by Schaffer synaptic potentials in the apical shaft constitute a necessary amplifier for this input to cause output decision. Local inhibition decides when and where an AP will initiate, constituting an efficient mechanism to discriminate and weight different inputs.

Action Potentials↗
PubMed1991

Synaptic responses of guinea pig cingulate cortical neurons in vitro.

1. Intracellular recordings were made from layer V/VI neurons of the guinea pig anterior cingulate cortex to investigate postsynaptic potentials (PSPs) evoked by electrical stimulation of the subcortical white matter (forceps minor). 2. Four distinct types of PSPs were recorded (at the resting potential) under normal physiological conditions; 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX)-sensitive excitatory postsynaptic potentials (EPSPs) were followed by bicuculline- or picrotoxin-sensitive depolarizing or hyperpolarizing inhibitory postsynaptic potentials (IPSPs), which were further followed by phaclofen-sensitive, long-lasting hyperpolarizing postsynaptic potentials (LPSPs). The average times-to-peak for the EPSP, depolarizing and hyperpolarizing IPSPs, and LPSP were 10, 22, 28, and 146 ms, respectively. 3. In the presence of CNQX and bicuculline, high-intensity electrical stimulation elicited a longer lasting EPSP with a time-to-peak of 21 ms. The amplitude and duration of the EPSP decreased with membrane hyperpolarization and increased with membrane depolarization. The EPSP was reversibly abolished by D,L-2-amino-5-phosphonovaleric acid (D,L-APV). 4. The bicuculline- or picrotoxin-sensitive depolarizing and hyperpolarizing IPSPs and the phaclofen-sensitive LPSP were markedly suppressed by CNQX, suggesting that glutamate (Glu) and/or aspartate nerve terminals project to GABAergic interneurons, and that the GABAergic interneurons are activated mainly by non-N-methyl-D-aspartate (non-NMDA) receptors. 5. In the presence of picrotoxin, the average reversal potential for the compound EPSP was 0 mV, which was similar to that (-6 mV) for the Glu-induced depolarization. In a solution containing D,L-APV at low concentrations, the average reversal potentials for the depolarizing and hyperpolarizing IPSPs and for the early and late components of the gamma-aminobutyric acid (GABA)-induced responses were -62, -72, -70, and -61 mV, respectively. Thus the value for the depolarizing IPSP was similar to that for the late response to GABA, whereas the value for the hyperpolarizing IPSP was almost the same as that for the early response to GABA. The average reversal potential of -90 mV for the LPSP was similar to -93 mV for the baclofen-induced hyperpolarization and to -94 mV for the spike afterhyperpolarization. 6. Application of phaclofen decreased the interspike interval of the spontaneous firing and reversed the increase in the interspike interval after subcortical stimulation. This result indicates that, even in a slice preparation, the anterior cingulate neurons are under tonic inhibitory control exerted by spontaneously active GABAergic interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1996

Physiological and pharmacological profile of trans-azetidine-2,4-dicarboxylic acid: metabotropic glutamate receptor agonism and effects on long-term potentiation.

In this study, we biochemically analysed the effects of the novel metabotropic glutamate receptor agonist trans-azetidine-2,4-dicarboxylic acid and examined its role in hippocampal long-term potentiation. In cell lines expressing metabotropic receptor 1 or 5 subtypes, the compound stimulated phosphoinositide hydrolysis with EC50 values of 189.4 +/- 6.4 and 32.2 +/- 8.3 microM, respectively. In hippocampal slices, trans-azetidine-2,4-dicarboxylic acid also increased phosphoinositide hydrolysis, yet failed to show any effect on forskolin-stimulated formation of cyclic AMP, even if 1 mM azetidine was applied. Since trans-azetidine-2,4-dicarboxylic acid (20 mM in 5 microliters) injected cerebroventricularly prolongs long-term potentiation induced by weak tetanization, a possible interaction with N-methyl-D-aspartate receptors was investigated using patch-clamp techniques. Neither facilitation of N-methyl-D-aspartate (500 microM) currents nor induction of non-specific currents was observed in the presence of 50 and 500 microM azetidine. Strong tetanus-induced long-term potentiation in the dentate gyrus of freely moving rats was not influenced by azetidine. In combination with the antagonist (R,S)-alpha-methyl-4-carboxyphenylglycine (200 mM in 5 microliters), however, the potentiation was attenuated and returned to baseline within 90 min. Blockade of N-methyl-D-aspartate receptors using 2-amino-5-phosphonopentanoate (20 mM in 5 microliters) prevented the potentiation in controls, but not in the azetidine group, where normal potentiation was observed for both the population spike amplitude and the excitatory postsynaptic potential. These data suggest that (i) trans-azetidine-2,4- dicarboxylic acid is an agonist at glutamate metabotropic receptors; (ii) a facilitation of induction and maintenance of long-term potentiation via N-methyl-D-aspartate receptors seems unlikely; and (iii) pharmacological activation of metabotropic receptors prior to tetanization appears to bypass the N-methyl-D-aspartate receptor dependence of the potentiation. In conclusion, a role for metabotropic glutamate receptors in both short-term and long-term potentiation is indicated by these data.

Animals↗