Biomedical subjects

P Dutar

Publications and source records attributed to P Dutar.

At least 19 recordsLinked to original sources

PubMed2002

Decrease in calbindin content significantly alters LTP but not NMDA receptor and calcium channel properties.

The contribution of the cytosolic calcium binding protein calbindin D(28K) (CaBP) to the synaptic plasticity was investigated in hippocampal CA1 area of wild-type and antisense transgenic CaBP-deficient mice. We showed that long-term potentiation (LTP) induced by tetanic stimulation in CaBP-deficient mice was impaired. The fundamental biophysical properties of NMDA receptors and their number were not modified in CaBP-deficient mice. We also demonstrated that the physiological properties of calcium channels were identical between genotypes. An insufficient Ca(2+) entry through NMDA receptors or calcium channels, or a decrease in NMDA receptor density are unlikely to explain this impairment of LTP. Interestingly, we showed that the loss of LTP was not prevented by glycine but was restored in the presence of a low concentration of the NMDA receptor antagonist D-APV (5 microM) and of the calcium chelator BAPTA-AM (5 microM). Moreover, we observed a loss of LTP in the wild-type mice when the postsynaptic tetanic-induced [Ca(2+)](i) rise is excessively increased. Conversely, a weaker tetanus stimulation allowed LTP induction and maintenance in CaBP-deficient mice. These results suggest that a higher cytosol [Ca(2+)](i), due to the decrease of CaBP expression may impair LTP induction and maintenance mechanisms without affecting the mechanisms of calcium entry. Thus, CaBP plays a critical role in long term synaptic plasticity by limiting the elevation of calcium rise in the cytosol to some appropriate spatio-temporal pattern.

Animals↗

PubMed2002

Spatial learning and synaptic hippocampal plasticity in type 2 somatostatin receptor knock-out mice.

Somatostatin is implicated in a number of physiological functions in the CNS. These effects are elicited through the activation of at least five receptor subtypes. Among them, sst2 receptors appear the most widely expressed in the cortex and hippocampal region. However, the specific role of this somatostatin receptor subtype in these regions is largely undetermined. In this study, we investigated the role of the sst2 receptor in the hippocampus using mice invalidated for the sst2 gene (sst2 KO mice). Complementary experimental approaches were used. First, mice were tested in behavioral tests to explore the consequences of the gene deletion on learning and memory. Spatial discrimination learning in the radial maze was facilitated in sst2 KO mice, while operant learning of a bar-pressing task was slightly altered. Mice were then processed for electrophysiological study using the ex vivo hippocampal slice preparation. Extracellular recordings in the CA1 area showed an enhancement in glutamatergic (AMPA and NMDA) responses in sst2 KO mice which displayed an increase in the magnitude of the short-term potentiation and long-term depression. In contrast, long-term potentiation was not significantly altered. Taken together, these data demonstrate that somatostatin, acting via sst2 hippocampal receptors, may contribute to a global decrease in glutamate efficiency and consequently alter glutamate-dependent plasticity and spatial learning.

Animals↗

PubMed2002

Somatostatin receptor subtypes 2 and 4 affect seizure susceptibility and hippocampal excitatory neurotransmission in mice.

We have investigated the role of somatostatin receptor subtypes sst2 and sst4 in limbic seizures and glutamate-mediated neurotransmission in mouse hippocampus. As compared to wild-type littermates, homozygous mice lacking sst2 receptors showed a 52% reduction in EEG ictal activity induced by intrahippocampal injection of 30 ng kainic acid (P < 0.05). The number of behavioural tonic-clonic seizures was reduced by 50% (P < 0.01) and the time to onset of seizures was doubled on average (P < 0.05). Seizure-associated neurodegeneration was found in the injected hippocampus (CA1, CA3 and hilar interneurons) and sporadically in the ipsilateral latero-dorsal thalamus. This occurred to a similar extent in wild-type and sst2 knock-out mice. Intrahippocampal injection of three selective sst2 receptor agonists in wild-type mice (Octreotide, BIM 23120 and L-779976, 1.5-6.0 nmol) did not affect kainate seizures while the same compounds significantly reduced seizures in rats. L-803087 (5 nmol), a selective sst4 receptor agonist, doubled seizure activity in wild-type mice on average. Interestingly, this effect was blocked by 3 nmol octreotide. It was determined, in both radioligand binding and cAMP accumulation, that octreotide had no direct agonist or antagonist action at mouse sst4 receptors expressed in CCl39 cells, up to micromolar concentrations. In hippocampal slices from wild-type mice, octreotide (2 micro m) did not modify AMPA-mediated synaptic responses while facilitation occurred with L-803087 (2 micro m). Similarly to what was observed in seizures, the effect of L-803087 was reduced by octreotide. In hippocampal slices from sst2 knock-out mice, both octreotide and L-803087 were ineffective on synaptic responses. Our findings show that, unlike in rats, sst2 receptors in mice do not mediate anticonvulsant effects. Moreover, stimulation of sst4 receptors in the hippocampus of wild-type mice induced excitatory effects which appeared to depend on the presence of sst2 subtypes, suggesting these receptors are functionally coupled.

Animals↗

PubMed2000

NMDA receptor activation in the aged rat hippocampus.

Age-related alterations of N-methyl-D-aspartate receptor (NMDAr) activation were investigated in the CA1 field of hippocampal slices from young (3-6 months old) and aged (25-33 months old) Sprague-Dawley rats by using ex vivo extracellular electrophysiological recording techniques. NMDAr-mediated field excitatory postsynaptic potentials (fEPSPs) were induced by electrical stimulation of glutamatergic fibers in a magnesium (Mg(2+))-free medium supplemented with the non-NMDAr antagonist CNQX. The fEPSPs were significantly smaller in aged rats, whereas the response of presynaptic afferent fibers remained unaffected. No significant age-related differences were found in the ability of Mg(2+) to depress the magnitude of NMDAr-mediated fEPSPs. The responsiveness of postsynaptic NMDAr to the agonist was assessed in both groups of animals. No age-related differences were recorded either in the depolarizing effect of bath-applied NMDA or in the magnitude of the depolarization after altering extracellular Mg(2+) concentration. Finally, short-term potentiation (STP) of excitatory transmission was studied in young and aged rats considering the pivotal role of NMDAr in synaptic plasticity. No age-related alterations of the magnitude and the time course of STP in response to 10 or 30Hz conditioning stimulation were found. Because of the decrease in the magnitude of NMDAr-mediated synaptic transmission in aged animals, the absence of obvious modifications of synaptic plasticity suggests the occurrence of compensatory mechanisms that are discussed.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed2000

Slow synaptic inhibition mediated by metabotropic glutamate receptor activation of GIRK channels.

Glutamate is the predominant excitatory neurotransmitter in the vertebrate CNS. Ionotropic glutamate receptors mediate fast excitatory actions whereas metabotropic glutamate receptors (mGluRs) mediate a variety of slower effects. For example, mGluRs can mediate presynaptic inhibition, postsynaptic excitation, or, more rarely, postsynaptic inhibition. We previously described an unusually slow form of postsynaptic inhibition in one class of projection neuron in the song-control nucleus HVc of the songbird forebrain. These neurons, which participate in a circuit that is essential for vocal learning, exhibit an inhibitory postsynaptic potential (IPSP) that lasts several seconds. Only a portion of this slow IPSP is mediated by GABA(B) receptors. Since these cells are strongly hyperpolarized by agonists of mGluRs, we used intracellular recording from brain slices to investigate the mechanism of this hyperpolarization and to determine whether mGluRs contribute to the slow synaptic inhibition. We report that mGluRs hyperpolarize these HVc neurons by activating G protein-coupled, inwardly-rectifying potassium (GIRK) channels. MGluR antagonists blocked this response and the slow synaptic inhibition. Thus, glutamate can combine with GABA to mediate slow synaptic inhibition by activating GIRK channels in the CNS.

Amino Acids, Dicarboxylic↗

PubMed1999

Glutamatergic synaptic responses and long-term potentiation are impaired in the CA1 hippocampal area of calbindin D(28k)-deficient mice.

The contribution of the cytosolic calcium binding protein calbindin D(28K) (CaBP) to glutamatergic neurotransmission and synaptic plasticity was investigated in hippocampal CA1 area of wild-type and antisense transgenic CaBP-deficient mice, with the use of extracellular recordings in the ex vivo slice preparation. The amplitude of non-N-methyl-D-aspartate receptor (non-NMDAr)-mediated extracellular field excitatory postsynaptic potentials (fEPSPs) recorded in control medium was significantly greater in CaBP-deficient mice, whereas the afferent fiber volley was not affected. In contrast, the amplitude of NMDAr-mediated fEPSPs isolated in a magnesium-free medium after blockade of non-NMDAr and GABAergic receptors was significantly depressed in these animals. No alteration in the magnitude of paired-pulse facilitation was found, indicating that the presynaptic calcium mechanisms controlling glutamate release were not altered in CaBP-deficient mice. The magnitude and time course of the short-term potentiation (STP) of fEPSPs induced by a 30 Hz conditioning stimulation, which was blocked by the NMDAr antagonist 2-amino-5-phosphonovalerate acid (2-APV), was not impaired in the transgenic mice, whereas long-term potentiation (LTP) induced by a 100 Hz tetanus was not maintained. The long-term depression (LTD) induced by low-frequency stimulation (1 Hz, 15 min) in the presence of the GABA antagonist bicuculline was not altered. These results argue for a contribution of CaBP to the mechanisms responsible for the maintenance of long-term synaptic potentiation, at least in part by modulating the activation of NMDA receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1999

Pharmacological characterization of an unusual mGluR-evoked neuronal hyperpolarization mediated by activation of GIRK channels.

The metabotropic glutamate receptor (mGluR) agonist ACPD exerts an unusual inhibitory effect on a population of neurons of the song-control nucleus HVc of the zebra finch via activation of the GIRK channel. We report in the present study the pharmacology of this response. ACPD directly hyperpolarized the neurons by a mechanism independent of GABA(B) receptors. The group I mGluR agonist DHPG had no effect on membrane properties and the group I mGluR antagonist 4-CPG did not affect the ACPD-induced hyperpolarization. In contrast, the ACPD response was mimicked by the group II mGluR agonist LY314593 and the group II and III agonist L-CCG-I. The group II mGluR antagonist LY307452 fully antagonized the ACPD response and reduced the response induced by L-CCG-I. The group III mGluR agonist L-AP4 induced a small hyperpolarization, which was antagonized by the group III mGluR antagonist MAP-4. These data indicate that group II and group III mGluRs are present and functional in the postsynaptic membrane of these HVc neurons, and mediate the hyperpolarizing action of mGluR agonists. In contrast, group I mGluRs are absent from these neurons, nonfunctional, or coupled to different effector systems that do not influence membrane potential or input resistance.

Animals↗

PubMed1998

Alteration of NMDA receptor-mediated synaptic responses in CA1 area of the aged rat hippocampus: contribution of GABAergic and cholinergic deficits.

Synaptic responses mediated by the N-methyl-D-aspartate receptor (NMDAr) and non-NMDAr activation were compared in CA1 hippocampal region of young (3-4 months old) and aged (25-33 months old) Sprague-Dawley rats with the use of ex vivo extracellular recordings techniques. In aged rats, the amplitude of the NMDAr-mediated field excitatory postsynaptic potentials (fEPSPs) was not altered, whereas their duration was significantly increased. In contrast, the magnitude of non-NMDAr-mediated fEPSPs was significantly smaller. The presynaptic fiber volley was not affected by age. Considering that the depression of non-NMDAr-mediated responses was previously attributed to fewer synaptic contacts between glutamatergic afferent fibers and pyramidal cells in aged animals (see Barnes et al., Hippocampus 1992;2:457-468), the absence of age-related changes in the amplitude of NMDAr-mediated fEPSPs suggests that compensatory mechanisms may occur. The contribution of gamma-aminobutyric acid (GABA) and acetylcholine to these mechanisms was addressed. The NMDAr-mediated fEPSPs were then recorded (1) in young and aged rats before and after blockade of the GABA(B) receptor-mediated inhibition by the specific antagonist CGP 55845 and (2) in young rats after a selective cholinergic denervation of the hippocampus by the immunotoxin 192 IgG-saporin. The results did not indicate statistically relevant age-related effects of CGP 55845. In contrast, the loss of the cholinergic innervation by the immunotoxin induced a significant increase in both the amplitude and duration of the NMDAr-mediated fEPSPs. Our results indicate that the functional properties of the ionotropic glutamate receptor subtypes located on CA1 pyramidal cells are differentially affected by aging and suggest that the cholinergic deficit that occurs during aging may be involved in the maintenance of robust NMDAr-mediated synaptic responses.

Acetylcholine↗

PubMed1998

Spatial discrimination learning and CA1 hippocampal synaptic plasticity in mdx and mdx3cv mice lacking dystrophin gene products.

Duchenne muscular dystrophy is frequently associated with a non-progressive cognitive deficit attributed to the absence of 427,000 mol. wt brain dystrophin, or to altered expression of other C-terminal products of this protein, Dp71 and/or Dp140. To further explore the role of these membrane cytoskeleton-associated proteins in brain function, we studied spatial learning and ex vivo synaptic plasticity in the mdx mouse, which lacks 427,000 mol. wt dystrophin, and in the mdx3cv mutant, which shows a dramatically reduced expression of all the dystrophin gene products known so far. We show that reference and working memories are largely unimpaired in the two mutant mice performing a spatial discrimination task in a radial maze. However, mdx3cv mice showed enhanced emotional reactivity and developed different strategies in learning the task, as compared to control mice. We also showed that both mutants display apparently normal levels of long-term potentiation and paired-pulse facilitation in the CA1 field of the hippocampus. On the other hand, an increased post-tetanic potentiation was shown by mdx, but not mdx3cv mice, which might be linked to calcium-regulatory defects. Otherwise, immunoblot analyses suggested an increased expression of a 400,000 mol. wt protein in brain extracts from both mdx and mdx3cv mice, but not in those from control mice. This protein might correspond to the dystrophin-homologue utrophin. The present results suggest that altered expression of dystrophin or C-terminal dystrophin proteins in brain did not markedly affect hippocampus-dependent spatial learning and CA1 hippocampal long-term potentiation in mdx and mdx3cv mice. The role of these membrane cytoskeleton-associated proteins in normal brain function and pathology remains to be elucidated. Furthermore, the possibility that redundant mechanisms could partially compensate for dystrophins' deficiency in the mdx and mdx3cv models should be further considered.

Animals↗

PubMed1998

Multiple cell types distinguished by physiological, pharmacological, and anatomic properties in nucleus HVc of the adult zebra finch.

Nucleus HVc of the songbird is a distinct forebrain region that is essential for song production and shows selective responses to complex auditory stimuli. Two neuronal populations within HVc give rise to its efferent projections. One projection, to the robust nucleus of the archistriatum (RA), serves as the primary motor pathway for song production, and can also carry auditory information to RA. The other projection of HVc begins a pathway through the anterior forebrain, (area X --> medial portion of the dorsolateral nucleus of the thalamus (DLM) --> lateral portion of the magnocellular nucleus of the anterior neostriatum (L-MAN) --> RA) that is crucial for song learning but, although active during singing, is not essential for adult song production. To test whether these different projection neuron classes have different functional properties, we recorded intracellularly from neurons in nucleus HVc in brain slices. We observed at least three classes of neuron based on intrinsic physiological and pharmacological properties as well as on synaptic inputs. We also examined the morphological properties of the cells by filling recorded neurons with neurobiotin. The different physiological cell types correspond to separate populations based on their soma size, dendritic extent, and axonal projection. Thus HVc neurons projecting to area X have large somata, show little spike-frequency adaptation, a hyperpolarizing response to the metabotropic glutamate receptor (mGluR) agonist (1S,3R)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD), and exhibit a slow inhibitory postsynaptic potential (IPSP) following tetanic stimulation. Those HVc neurons projecting to motor nucleus RA have smaller somata, show strong accommodation, are not consistently hyperpolarized by ACPD, and exhibit no slow IPSP. A third, rarely recorded class of neurons fire in a sustained fashion at very high-frequency and may be interneurons. Thus the neuronal classes within HVc have different functional properties, which may be important for carrying specific information to their postsynaptic targets.

Animals↗

PubMed1997

Is activation of the metabotropic glutamate receptors impaired in the hippocampal CA1 area of the aged rat?

The effects of aging on activation of metabotropic glutamate (mGlu) receptors were studied in the CA1 field of hippocampal slices from young (3- to 4-month-old) and aged (24- to 27-month-old) Sprague-Dawley rats with the use of ex vivo electrophysiological recording techniques. The depolarization of membrane potential, the increase in input resistance, and the blockade of the afterhyperpolarization induced in pyramidal cells of young rats by bath application of the mGlu receptor agonist (+/-)-trans-1-aminocyclopentate-1,3-dicarboxylic acid were not altered in aged animals. No age-related changes of the depressive effects of the mGlu receptor agonist were found on either the excitatory glutamatergic postsynaptic potential or the GABA-mediated inhibitory postsynaptic potentials induced by the stimulation of the stratum radiatum. The magnitude of synaptic plasticity involving mGlu receptor activation, although weaker, was not significantly altered in aged rats. This absence of age-related effects on activation of mGlu receptors may be important in understanding the possible origins of the alterations in neuronal plasticity which occur in brain aging.

2-Amino-5-phosphonovalerate↗

PubMed1997

Potentiation of glutamatergic EPSPs in rat CA1 hippocampal neurons after selective cholinergic denervation by 192 IgG-saporin.

A complete and selective destruction of the basal forebrain cholinergic neurons projecting to the cerebral cortex and the hippocampus was induced in the rat by the toxin 192 IgG-saporin. Using electrophysiologic techniques, we have investigated the consequences of this cholinergic denervation on inhibitory and excitatory synaptic responses of CA1 pyramidal cells in rat hippocampal slices ex vivo. Histochemical experiments were performed in slices from control and 192 IgG-saporin-treated rats to check the efficacy of the intracerebroventricular injection of the immunotoxin. Stimulation of stratum radiatum elicits a glutamatergic excitatory postsynaptic potentials followed by a biphasic GABAergic inhibitory postsynaptic potential (IPSP). No significant change in IPSP was observed in 192 IgG-saporin-treated rats. By contrast, the N-methyl-D-aspartate (NMDA) and to a lesser extent the non-NMDA components of the glutamatergic response were potentiated in these animals. The possible pre- and postsynaptic mechanisms of this potentiation were discussed.

Animals↗

PubMed1997

Synaptic functions in the aged rat hippocampus: a target for corticosteroids?

The role of corticosteroids in brain aging remains a controversial issue. Conceivably, if corticosteroids levels are increased in the aged brain, neuronal function might be altered. For instance, GABA-mediated synaptic events, spike accommodation and afterhyperpolarizing potentials (AHPs) might be modified. Our electrophysiological results show that the most consistent alterations observed in the aged rat hippocampus concern cholinergic receptors, glutamatergic NMDA receptors and GABAB receptors mediated synaptic potentials. In contrast no consistent alterations were observed in afterhyperpolarizing potentials, calcium spikes, or GABAA mediated synaptic events. Therefore our electrophysiological results are difficult to reconcile with a 'glucocorticoid cascade hypothesis,' involving an elevated level of corticosterone in the aged rat.

Adrenal Cortex Hormones↗

PubMed1996

Deficits in memory and hippocampal long-term potentiation in mice with reduced calbindin D28K expression.

The influx of calcium into the postsynaptic neuron is likely to be an important event in memory formation. Among the mechanisms that nerve cells may use to alter the time course or size of a spike of intracellular calcium are cytosolic calcium binding or "buffering" proteins. To consider the role in memory formation of one of these proteins, calbindin D28K, which is abundant in many neurons, including the CA1 pyramidal cells of the hippocampus, transgenic mice deficient in calbindin D28K have been created. These mice show selective impairments in spatial learning paradigms and fail to maintain long-term potentiation. These results suggest a role for calbindin D28K protein in temporally extending a neuronal calcium signal, allowing the activation of calcium-dependent intracellular signaling pathways underlying memory function.

Animals↗

PubMed1996

Persistence of CA1 hippocampal LTP after selective cholinergic denervation.

The possible role of endogenous cholinergic innervation in hippocampal plasticity is controversial. We studied the role of acetylcholine (ACh) in short- and long-term potentiation (STP and LTP), using the cholinergic neurotoxin 192 IgG-saporin. It was still possible to induce STP the LTP in the CA1 field following complete and selective cholinergic denervation of the hippocampus. This study therefore demonstrates that integrity of the endogenous cholinergic system is not necessary for the induction or maintenance of LTP in the CA1 field of the hippocampus. The consequences in terms of relationship between hippocampal cholinergic system, LTP and memory are discussed.

Acetylcholine↗

PubMed1996

Synaptic mechanisms and calcium binding proteins in the aged rat brain.

Synaptic mechanisms were studied ex vivo in the aged rat hippocampus, using a slice preparation and intracellular electrophysiological recordings of the CA1 pyramidal neurons. A dramatic depression of the slow cholinergic excitatory postsynaptic potential (EPSP) and of the slow, GABAB-mediated inhibitory postsynaptic potential (IPSP) were observed. These age-related changes were consistently found in three different strains of rats. The mechanisms involve 1) changes in the properties of the postsynaptic muscarinic receptors, and possibly in acetylcholine release (for the postsynaptic muscarinic receptors, and possbily in acetylcholine release (for the cholinergic EPSP), and 2) alterations in the presynaptic GABAergic interneurons, as shown by a loss in calbindin immunoreactivity (for the GABAergic IPSP). The immunoreactivity for three calcium binding proteins (calbindin, parvalbumin and calretinin) was studied in the aged rat brain. Immunoreactivity for calbindin was dramatically reduced in the pyramidal neurons of the CA1 field and in a subpopulation of interneurons in the hippocampus. Immunoreactivity for parvalbumin was reduced in the medial septal area, and in the cingulate cortex, whereas no change was observed for calretinin. These age-related alterations could 1) modify the functions of the hippocampal networks, and possibly contribute to the age-related cognitive deficits, and 2) compromise intraneuronal calcium buffering, and thus make neurons more vulnerable to toxic insults.

Animals↗

PubMed1995

Presynaptic depression of inhibitory postsynaptic potentials by metabotropic glutamate receptors in rat hippocampal CA1 pyramidal cells.

The effects of the metabotropic glutamate (mGlu) receptor agonists (+/-)-trans-1-aminocyclopentane-1,3-dicarboxylic acid (trans-ACPD) or 1S,3R-ACPD on gamma-aminobutyric acid (GABA)-mediated inhibitory synaptic responses have been investigated in vitro in CA1 pyramidal cells of rat hippocampal slices. Bath application of both agonists depolarized the resting membrane potential and increased membrane resistance. Simultaneously, the afterhyperpolarization induced by a burst of spikes as well as spike accomodation were blocked. Stimulation of the stratum radiatum induced in CA1 pyramidal cells an early excitatory postsynaptic potential (EPSP) followed by a fast GABAA and a slow GABAB-mediated inhibitory postsynaptic potentials (IPSPs). All synaptic responses were dose dependently depressed by mGlu receptor agonists. At low concentration, (+/-)-trans-ACPD (10-100 microM) and 1S,3R-ACPD (10 microM) consistently reduced the EPSP, slightly depressed the fast IPSP but greatly decreased the slow IPSP. Increasing the concentration of mGlu receptor agonists to 200 microM and 50 microM, respectively further depressed the EPSP and dramatically reduced the amplitude of both IPSPs. In the presence of the glutamate receptor antagonists 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM) and D-(-)-2-amino-5-phosphonovaleric acid (30 microM), monosynaptically evoked IPSPs were still depressed by mGlu receptor agonists. In the same conditions, the discharge frequency of spontaneous IPSPs which reflect the activity of GABAergic interneurons was enhanced by low doses of mGlu receptor agonists but depressed with higher concentrations. On the other hand, the postsynaptic hyperpolarization and decrease in membrane resistance induced by the GABAB receptor agonist baclofen applied in the bath or by microiontophoresis were not affected by mGlu receptor agonists.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Decreased monosynaptic GABAB-mediated inhibitory postsynaptic potentials in hippocampal CA1 pyramidal cells in the aged rat: pharmacological characterization and possible mechanisms.

1. gamma-Aminobutyric acid (GABA)-mediated inhibitory postsynaptic potentials (IPSPs) were compared in young and aged rats in CA1 area of the rat hippocampus, with the use of the in vitro intracellular recording technique. D-2-Amino-5-phosphonovaleric acid (APV) and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) were used to suppress synaptic potentials mediated by the excitatory amino acids. 2. Under these conditions, stimulation of the stratum radiatum elicited a monosynaptic fast GABAA (fIPSP) and a slow GABAB (sIPSP)-mediated IPSP. The fIPSP and the sIPSP were further isolated in the presence of the GABAB antagonist CGP 35348 or the GABAA antagonists bicuculline or picrotoxin. No age-related changes were observed in the amplitude and the duration of the fIPSP. In contrast, the amplitude (but not the duration) of the sIPSP was significantly reduced in the aged rat. 3. The postsynaptic hyperpolarization and increase in membrane conductance induced in pyramidal cells by bath application of the GABAB agonist baclofen were comparable in both groups of animals, indicating that the postsynaptic GABAB receptors are not altered in the aged rats. 4. Paired-pulse depression of IPSPs was used in young and aged rats to study possible alterations in GABA release or in presynaptic GABAB receptors that control GABA release. When fIPSPs were isolated by bath application of tetrahydro-9-aminoacridine (THA), no significant difference in the magnitude of the paired-pulse depression was observed between young and aged rats. A similar result was found with the paired-pulse depression of isolated sIPSPs in the presence of bicuculline or picrotoxin.(ABSTRACT TRUNCATED AT 250 WORDS)

6-Cyano-7-nitroquinoxaline-2,3-dione↗