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P Dutar

Publications and source records attributed to P Dutar.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1994

Loss of calbindin-immunoreactivity in CA1 hippocampal stratum radiatum and stratum lacunosum-moleculare interneurons in the aged rat.

Alterations in hippocampal circuitry may underly age-related learning and memory impairment. We showed in a previous study that the GABAB-mediated slow inhibitory postsynaptic potential (IPSP) induced in CA1 pyramidal neurons by electrical stimulation of stratum radiatum, is depressed in the hippocampus of the aged rat. This could be due to alterations in GABAergic interneuron functions. We report in this study that the number of hippocampal calbindin-immunoreactive (CaBP-IR) GABAergic interneurons is decreased in the aged rat. The mean number of CaBP-IR interneurons per slice decreases by 50% in the aged rat. The most severe loss was observed in the stratum radiatum of CA1 (78%), with a less consistent loss of immunoreactivity in CA3 (35%). In contrast, the mean number of interneurons containing parvalbumin (PV), was not significantly decreased in the aged rat. Our results show a loss of CaBP immunoreactivity in a population of GABAergic interneurons, which might be related to an altered function of these interneurons and consequently of GABAergic synaptic transmission in the aged rat. In contrast, PV immunoreactivity in interneurons located close to the pyramidal layer does not decrease in the hippocampus of the aged rat.

Aging↗
PubMed1994

Cholinergic denervation of the rat hippocampus by 192-IgG-saporin: electrophysiological evidence.

The consequences of intracerebroventricular injection of the toxin 192-IgG-saporin on the electrophysiological properties of CA1 pyramidal cells were investigated using intracellular recordings in the in vitro hippocampal slice preparation. We present the first electrophysiological evidence of a dysfunction of hippocampal cholinergic afferents following injection of 192-IgG-saporin. The synaptic events mediated by acetylcholine were altered in such animals: the slow cholinergic excitatory postsynaptic potentials as well as the cholinergic activation of GABAergic interneurones were dramatically depressed or even absent; the amplitude and duration of the afterhyperpolarization following a burst of spikes were increased, while other neuronal properties were not modified. These specific alterations suggest that the toxin 192-IgG-saporin is a specific tool for the experimental study of cholinergic denervation in the hippocampus.

Animals↗
PubMed1994

[Aging of memory mechanisms].

Human amnesia cases (after surgical removal of the hippocampi or brain anoxia) have clearly established the critical role of the hippocampal formation in anterograde amnesia. Other parts of the brain may also contribute to anterograde amnesia (mammillary bodies, medial thalamus). In neurodegenerative diseases (and specially in Alzheimer's disease) amnesia is often the prominent symptom, but the brain lesions are not restricted to the hippocampal formation. In Alzheimer's disease they involve also the cerebral cortex and several subcortical nuclei. Physiological brain aging is also associated with some degree of memory impairment, but much less severe than in Alzheimer's disease. The issue of the nature and the mechanisms of the memory impairment associated with age and with Alzheimer's disease is very important, because the frequency of these problems increases dramatically as the populations of the world is growing older. There is some evidence that neuronal loss and alterations in neurotransmitter systems occur in the aged subject, but the relationship between such changes and the age-related memory deficit is far from being clear. In Alzheimer's disease, the loss of memory is likely to be due to neuronal loss in cerebral cortex and hippocampal formation, along with alterations in neurotransmitter systems (specially cholinergic, monoaminergic and aminoacidergic systems). The work in experimental animals has largely confirmed the critical role of the hippocampal formation, as well as identified other critical structures. The mechanisms of the age-related memory impairment can be to some extent investigated in aged animals. In the aged rat there is evidence that several neurotransmitter networks are altered. Alteration in the dopaminergic and cholinergic systems have been extensively studied, but the involvement of other systems is likely. Learning and memory deficits are consistently observed in a sub-population of aged rodents (as well as in other species including non-human primates). For instance some aged rats do have a deficit in the performance of a spatial learning task such as the "water maze". There is some evidence that this deficit is due, at least in part, to alterations in the functions of the hippocampal formation. In other words, if aged rats have a spatial memory deficit, it might be due to changes in hippocampal neuronal circuitry. The study of age-related alterations in hippocampal neuronal networks, using electrophysiological techniques have shown that several neuronal properties such as resting membrane potential, membrane resistance or sodium spike amplitude are not altered in the aged rat hippocampus.(ABSTRACT TRUNCATED AT 400 WORDS)

Aged↗
PubMed1993

Cholinergic and non-cholinergic synaptic mechanisms in the aged rat hippocampus.

We compared age-related alterations in the electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons in three strains of rats (Sprague-Dawley, Fisher 344 and Wistar) at 3-4 and 25-32 months of age, using the in vitro slice preparation. The most consistent age-related alterations were: a decrease in membrane excitability, a decrease in the amplitude and duration of inhibitory postsynaptic potentials and a decreased sensitivity to the effect of the cholinergic agonist carbachol. In contrast, no consistent alterations in calcium-dependent events were observed in these strains of rats. The age-related changes in the duration of the after-hyperpolarization (AHP) were different (and even opposite) depending on the strain studied. Our results show that age-related changes observed in a given strain are not necessarily present in all strains of the same species.

Aging↗
PubMed1993

Different effects of omega-conotoxin GVIA at excitatory and inhibitory synapses in rat CA1 hippocampal neurons.

The nature of the coupling mechanism of presynaptic calcium channels involved in the release of neurotransmitters in the mammalian central nervous system is unknown. Using intracellular recordings from CA1 neurons in the rat hippocampal slice preparation, we show that the N-type calcium channels antagonist omega-conotoxin GVIA (omega-CgTx) blocks partially the excitatory (EPSP) and totally the inhibitory (IPSP) synaptic transmission in CA1 hippocampal pyramidal neurons. In addition, the inhibitory effect of omega-CgTx on IPSPs is strongly depressed by intrahippocampal injection of PTX, while the effect on EPSP is not. The results suggest that the nature or the regulation of calcium channels might be different, depending on the location of these channels on excitatory or inhibitory terminals.

2-Amino-5-phosphonovalerate↗
PubMed1993

Presynaptic inhibitory effect of baclofen on hippocampal inhibitory synaptic transmission involves a pertussis toxin-sensitive G-protein.

The involvement of a pertussis toxin (PTX)-sensitive G-protein in the activation of presynaptic GABAB receptor is controversial. In the present study, we reinvestigated the problem using intracellular recordings from CA1 neurons in rat hippocampus slices. We showed that the presynaptic inhibitory effect of baclofen is mediated differently at excitatory and inhibitory synapses. Excitatory (e.p.s.p.) and inhibitory (i.p.s.p.) postsynaptic potentials were strongly antagonized by baclofen in control rats. Three days after administration of PTX into the stratum radiatum of the hippocampus, the inhibitory effect of baclofen on i.p.s.p. was antagonized. In contrast, the inhibitory effect on e.p.s.p. was partly maintained. These results suggest that different sub-types of GABAB receptors exist on nerve terminals with different transduction mechanisms. GABAB receptors located on GABAergic inhibitory terminals are linked to a PTX-sensitive G-protein, whereas those located on excitatory terminals could consist of a PTX-sensitive type and a PTX-insensitive type. In addition, we showed that part of the inhibitory effect of baclofen at excitatory synapses is independent of omega-conotoxin (omega-CgTx)-sensitive N-type Ca2+ channels.

Animals↗
PubMed1992

Alterations in the properties of hippocampal pyramidal neurons in the aged rat.

The electrophysiological and pharmacological properties of CA1 hippocampal pyramidal neurons were studied in slices from young (three to four months) and aged (25-32 months) Sprague-Dawley rats having previously performed two behavioral tasks. About 20% of the aged rats were impaired in either the spontaneous alternation task or the water maze task. Electrophysiological parameters were measured and compared in young and aged animals using intracellular recordings. No age-related differences were observed in membrane potential, input resistance, amplitude of action potentials or amplitude of calcium spikes. The amplitude and duration of individual afterhyperpolarizations following a single spike were unchanged. In contrast, the neuronal excitability was significantly decreased and the spike duration significantly enhanced in aged rats as compared to young rats. The comparison of afterhyperpolarizations (which follow a burst of spikes) between young and aged rats was more complex. An increase in the amplitude and duration of afterhyperpolarizations generally occurred in aged animals. However, this increase was not consistent among animals and was dependent on the holding potential of the neuron and on the number of action potentials used to trigger the afterhyperpolarization. The depolarizing effect of bath-applied carbachol, as well as the associated increase in membrane resistance were reduced in neurons from aged rats. In contrast, the effects of carbachol on the depression of synaptic events and the blockade of the afterhyperpolarizations were similar in young and aged animals. In addition, the amplitude of the slow cholinergic excitatory postsynaptic potential induced by stimulation of cholinergic afferents in the presence of physostigmine was also decreased in aged rats. Excitatory postsynaptic potentials and inhibitory postsynaptic potentials following electrical stimulation of stratum radiatum were compared. The amplitude and duration of excitatory postsynaptic potentials were increased in aged rats. The amplitude and duration of the fast inhibitory postsynaptic potential were not significantly affected in aged animals. In contrast, the duration of the slow inhibitory postsynaptic potential was decreased in aged rats. Since the mean baclofen-induced hyperpolarization was only slightly reduced in aged rats, the most likely explanation is a decrease in the release of GABA rather than an alteration in the postsynaptic response mediated by GABAB receptors. A statistically significant correlation was found between the degree of impairment in the spontaneous alternation task and the amplitude of the carbachol-induced depolarization.

Acetylcholine↗
PubMed1991

Effects of calcium channel agonist and antagonists on calcium-dependent events in CA1 hippocampal neurons.

The effects of a variety of calcium channel modulators on different calcium-dependent events in CA1 pyramidal hippocampal neurons were analysed using intracellular recordings in an in vitro slice preparation. The following substances were tested: the dihydropyridine calcium agonist BAY K 8644, the dihydropyridine calcium antagonist nimodipine, the phenylalkylamine verapamil and the snail toxin omega-conotoxin GVIA (omega-CgTx). BAY K 8644 increased the repolarization time of the after hyperpolarization (AHP) following a spike burst. This effect was antagonized by nimodipine. BAY K 8644 also prolonged the calcium spike and, in some cases, increased the size of the synaptic events resulting from activation of the Schaffer collateral/commissural system. Nimodipine decreased the size of the AHP in some neurons but had no consistent effect on synaptic events. Verapamil at low concentrations (1-10 microM) had no significant effects on the calcium-dependent events in the hippocampus. Increasing the concentration (up to 100 microM) led to a progressive suppression of the AHP and of the slow inhibitory postsynaptic potential (IPSP), probably via an action on potassium conductances. In addition, the baclofen-induced hyperpolarization was blocked by verapamil. Interestingly, at this higher concentration, verapamil could suppress the AHP without depressing the calcium spike. omega-CgTx selectively blocked the synaptic events (especially the IPSPs) but had no effect on non-synaptic events. This last compound exhibits a high degree of selectivity, acting on N-type calcium channels which are involved in neurotransmitter release. Our results provide evidence that different classes of agents which act on calcium channels can be used to discriminate between different calcium-dependent responses in CA1 hippocampal neurons.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1990

Effects of tetrahydro-9-aminoacridine on cortical and hippocampal neurons in the rat: an in vivo and in vitro study.

The effects of tetrahydro-9-aminoacridine (THA), an anticholinesterase drug, have been studied in the rat both in vivo (cerebral cortex) and in vitro (CA1 field of the hippocampus) and compared with those of physostigmine. In the cerebral cortex THA potentiated the excitatory effect of acetylcholine in most neurons, including cortical neurons recorded from chronic unanesthetized animals. In vitro, THA (but not physostigmine) had a depolarizing, atropine- and tetrodotoxin-insensitive effect. This effect is associated with an increase in membrane resistance which suggests a direct effect of THA on hippocampal neurons. In addition THA blocked the slow inhibitory postsynaptic potential. At the same concentration THA potentiated the slow cholinergic excitatory postsynaptic potential produced by electrical stimulation of the cholinergic afferents. Its potency was, however, about 10 times lower than that of physostigmine. These results show that THA: (1) is an anticholinesterase much less potent than physostigmine; but (2) has also direct effects on central neurons, not observed with physostigmine and unrelated to its anticholinesterase activity.

Action Potentials↗
PubMed1990

[Effect of verapamil independent of its calcium channel antagonist action on hippocampal pyramidal neurons in rats].

The effects of verapamil, the phenylalkylamine calcium channel antagonist, have been studied on rat hippocampal pyramidal neurons, using intracellular recordings in an in vitro slice preparation. At low concentrations (1-10 microM), verapamil had no effect on these neurons. At higher concentrations (100-150 microM), it induced a progressive blockade of the slow component of the after-hyperpolarizing potential (AHP), but did not affect the fast one. Verapamil also blocked the slow inhibitory postsynaptic potential (sIPSP), but not the fast one. Pharmacological responses to the application of baclofen and serotonin were abolished, while the response to GABA was not. In addition, the size of the calcium spike was increased by verapamil, while the AHP and the sIPSP were already blocked. These results suggest that verapamil, applied at high concentrations, has an inhibitory effect on potassium conductances, independent of its calcium antagonist property.

Action Potentials↗
PubMed1989

Omega-conotoxin GVIA blocks synaptic transmission in the CA1 field of the hippocampus.

The effects of omega-conotoxin GVIA (omega-CgTx), a peptide isolated from the venom of a marine mollusc, were studied in rat hippocampal neurons. Intracellular recordings from the CA1 area were made for the purpose in in vitro slice preparations. Omega-CgTx (0.1-1 microM) rapidly and irreversibly blocked the EPSP and the IPSPs elicited by electrical stimulation of Schaffer collaterals/commissural fibers. Omega-CgTx also blocked the slow cholinergic EPSP induced by electrical stimulation of cholinergic afferents. The postsynaptic effects of baclofen or carbachol remained unchanged in the presence of omega-CgTx and other postsynaptic calcium-dependent events such as afterhyperpolarization were not affected by omega-CgTx. These results suggest a presynaptic action of omega-CgTx through the blockade of neurotransmitter release. Omega-CgTx might act in the hippocampus by blocking presynaptic N-type voltage-sensitive calcium channels.

Animals↗
PubMed1989

Galanin blocks the slow cholinergic EPSP in CA1 pyramidal neurons from ventral hippocampus.

Using intracellular recordings from slice preparations, we studied the effects of the peptide galanin on the properties of CA1 pyramidal neurons from rat ventral hippocampus. Galanin, applied in the superfusing medium, had a weak and inconsistent effect on the membrane potential or on the afterhyperpolarization which follows a train of spikes. Galanin, which is localized in some cholinergic neurons of the septo-hippocampal pathway, did not affect the action of acetylcholine or carbachol on CA1 pyramidal neurons. However, it did have a presynaptic inhibitory effect on the cholinergic terminals, blocking the slow cholinergic excitatory post-synaptic potential (EPSP) induced by the release of endogenous acetylcholine on the pyramidal neurons. This effect was reversible and mimicked by atropine. These results suggest that the peptide galanin, colocalized with acetylcholine in some septo-hippocampal neurons might play a role in the control of acetylcholine release.

Animals↗
PubMed1989

Pharmacological characterization of muscarinic responses in rat hippocampal pyramidal cells.

Intracellular recording from hippocampal CA1 pyramidal cells was used to characterize the pharmacological properties of muscarinic responses. Results obtained with the M1 antagonist pirenzepine and the M2 antagonist gallamine suggest that an M1 muscarinic receptor is involved in the muscarinic-induced membrane depolarization and blockade of the afterhyperpolarization (AHP). On the other hand, an M2 receptor may be involved in the cholinergic depression of the EPSP and the blockade of the potassium current termed the M-current. Pretreatment of hippocampi with pertussis toxin did not prevent any of the muscarinic responses suggesting that a pertussis toxin-sensitive G-protein is not involved. The M-current, in contrast to the other muscarinic actions, was unaffected by muscarinic agonists which are weak at increasing phosphoinositide (PI) turnover and actually blocked the action of full agonists. This finding suggests that stimulation of PI turnover may be involved in the blockade of the M-current. Although activation of protein kinase C with phorbol esters has little effect on the M-current, intracellular application of inositol trisphosphate did reduce the M-current. We were unable to establish any clear relationship between biochemical effector systems and the muscarinic receptor subtypes.

Animals↗
PubMed1989

Rhythmical bursting activity and GABAergic mechanisms in the medial septum of normal and pertussis toxin-pretreated rats.

The possible involvement of GABA in the control of the rhythmical bursting activity (RBA) of septo-hippocampal neurons (SHNs) has been studied in the rat in vivo. The discharge frequency of SHNs was modified by the iontophoretic application of a GABA agonist and antagonist as well as by the application of the GABA uptake blocker, nipecotic acid. The GABAB agonist baclofen inhibited the SHNs' activity, this effect being antagonized by the GABAB antagonist phaclofen. However, these different pharmacological manipulations did not modify the RBA frequency. Pretreatment of the rats with pertussis toxin, a substance which is known to block the events mediated by G-proteins (Gi or Go), decreased the RBA frequency. Neither agonists nor antagonists of GABAA or GABAB types had significant effects on the rhythmical bursting activity of SHNs. The effect of pertussis toxin suggests that other neurotransmitters or intrinsic mechanisms involving a G-protein influence this rhythm.

Action Potentials↗