Biomedical subjects

P Dutar

Publications and source records attributed to P Dutar.

At least 55 records · Page 3Linked to original sources

PubMed1989

Involvement of a pertussis toxin-sensitive G-protein in the pharmacological properties of septo-hippocampal neurones.

1. The physiological and pharmacological properties of identified septo-hippocampal neurones (SHNs) have been studied in rats pretreated with the bacterial toxin, pertussis toxin (PTX). 2. In rats anaesthetized with urethane and pretreated with PTX, the axonal conduction velocity was unchanged while the mean spontaneous activity was significantly increased. 3. PTX pretreatment had no effect on responses of SHNs to the iontophoretic application of gamma-aminobutyric acid (GABA) and cholinoceptor agonists (acetylcholine or carbachol). 4. Baclofen and 5-hydroxytryptamine (5-HT), almost exclusively inhibitory in control rats, had little effect or an excitatory effect in PTX pretreated rats. 5. These results suggest the involvement of a pertussis toxin-sensitive G-protein in responses medicated by 5-HT and GABAB-receptors but not in responses mediated by cholinoceptors and GABAA-receptors in medial septum neurones projecting into the hippocampus.

Animals↗

PubMed1988

A physiological role for GABAB receptors in the central nervous system.

The role of GABA in synaptic transmission in the mammalian central nervous system is more firmly established than for any other neurotransmitter. With virtually every neuron studied, the synaptic action of GABA is mediated by bicuculline-sensitive GABAA receptors which selectively increase chloride conductance. However, it has been shown that GABA has a presynaptic inhibitory action on transmitter release that is insensiive to bicuculline and is selectively mimicked by baclofen. The receptors involved in this action are referred to as GABAB receptors, to distinguish them from the classic bicuculline-sensitive GABAA receptors. In hippocampal pyramidal cells an additional postsynaptic action of GABA and baclofen has been reported that is also insensitive to GABAA antagonists, and may be mediated by GABAB receptors on the postsynaptic neuron. This action of GABA and baclofen involves an increase in potassium conductance. Synaptic activation of pathways converging on hippocampal pyramidal cells results in a slow inhibitory postsynaptic potential which involves an increase in potassium conductance, and it has been suggested that GABAB receptors might be responsible for this synaptic potential. However, to establish convincingly that GABAB receptors are physiologically important in the central nervous system, a selective GABAB antagonist is required. Here we provide this missing evidence. Using the hippocampal slice preparation, we now report that the phosphonic acid derivative of baclofen, phaclofen, is a remarkably selective antagonist of both the postsynaptic action of baclofen and the bicuculline-resistant action of GABA, and that it selectively abolishes the slow inhibitory postsynaptic potential in pyramidal cells.

Action Potentials↗

PubMed1988

Somatosensory cortical neurons with an identifiable electrophysiological signature.

In both cats and rats, neurons with a distinctively narrow action potential were recognized as a small subset of all neurons isolated in the somatosensory cortex. These cells were characterized by generally having a spontaneous activity, some evidence of an afferent input, a sensitivity to glutamate but a relative resistance to depolarization block induced by glutamate and a marked insensitivity to acetylcholine. Two were filled with horseradish peroxidase (HRP) and recovered. Although others have suggested that such neurons are interneurons, following reconstruction it was apparent that the two cells filled with HRP were pyramidal cells. These observations suggest that there may be more than one class of cortical neurons with thin spikes.

Action Potentials↗

PubMed1988

Stimulation of phosphatidylinositol (PI) turnover may mediate the muscarinic suppression of the M-current in hippocampal pyramidal cells.

The mechanism involved in the muscarinic blockade of the M-current was examined in hippocampal pyramidal cells. Muscarinic agents which are full agonists at stimulating phosphatidylinositol (PI) turnover, such as oxotremorine-M, block the M-current, while those agents which are weak agonists, such as oxotremorine, had little effect on the M-current. These results strongly suggest that PI turnover is involved in the muscarinic blockade of the M-current. Although activation of protein kinase C failed to block the M-current, intracellular application of inositol trisphosphate (IP3) reproducibly reduced the M-current. Further experiments will be required to determine if the action of IP3 requires a rise in intracellular calcium.

Animals↗

PubMed1988

Effect of psychotropic drugs on identified septohippocampal neurons.

The effects of various psychotropic drugs (benzodiazepines, antidepressants, neuroleptics and nootropic drugs, a family of cognition activator agents) on firing rates of septohippocampal neurons, identified by electrical antidromic stimulation, were studied in the medial septum-nucleus of the diagonal band of Broca of rats anaesthetized with urethan. Extracellular potentials from single septohippocampal neurons were recorded using glass pipettes. Drugs were applied by either microiontophoresis or intravenous injections (i.v.). Benzodiazepines produced a marked depression of spontaneous firing rates of septohippocampal neurons whether applied i.v. (diazepam) or iontophoretically (flurazepam, midazolam). In addition, diazepam had a potent depressant effect on the rhythmically bursting activity of the septohippocampal neurons. Baclofen also had an inhibitory effect. Antidepressant drugs (applied by iontophoresis) as well as amphetamine, had a depressant effect on spontaneous firing rates. Neuroleptics (i.v.) had less significant or consistent effects on septohippocampal neurons, although the effects of haloperidol were usually inhibitory. Nootropic drugs were generally ineffective. These data indicate that most psychotropic drugs tested (with the exception of nootropic drugs) have an inhibitory effect on the spontaneous activity of septohippocampal neurons. However, benzodiazepines seem to be more active than antidepressants or neuroleptics. Oxotremorine (i.v.) had a potent excitatory effect on septohippocampal neurons. Atropine (i.v.) increased the septohippocampal neurons' firing rate in some cases. These results are discussed in view of the possible implication of the involvement of septohippocampal neurons in the mediation of the effects of psychotropic drugs on the central nervous system and, more specifically, on the cholinergic systems.

Animals↗

PubMed1988

Pre- and postsynaptic GABAB receptors in the hippocampus have different pharmacological properties.

Pharmacological properties of pre- and postsynaptic GABAB receptors were compared in CA1 hippocampal pyramidal neurons in vitro. The postsynaptic effects mediated by GABAB receptors, i.e., the baclofen-induced hyperpolarization, the bicuculline-resistant GABA response, and the slow inhibitory postsynaptic potential elicited by CA1 afferent stimulation, are all blocked by pertussis toxin (which inactivates some G proteins). These events are also suppressed by stimulating protein kinase C by phorbol esters and blocked by the selective GABAB antagonist phaclofen. In contrast, the baclofen-induced presynaptic depression of the excitatory postsynaptic potential elicited by CA1 afferent stimulation is resistant to the action of pertussis toxin and is not antagonized by phaclofen. However, this presynaptic inhibition can be antagonized by phorbol esters. These results indicate that the pre- and postsynaptic effects mediated by GABAB receptors in hippocampus have distinctly different pharmacological properties and possibly a different coupling mechanism.

Action Potentials↗

PubMed1988

An iontophoretic study of single somatosensory neurons in rat granular cortex serving the limbs: a laminar analysis of glutamate and acetylcholine effects on receptive-field properties.

1. Glutamate, acetylcholine (ACh), and bicuculline were delivered by iontophoretic pipettes to the 545 neurons described in the preceding paper. Their response properties were examined to determine the effect of these compounds on the behavior of neurons in rat somatosensory cortex. 2. The responses to glutamate covered a broad range. Some cells were completely depolarized by small amounts of this excitatory amino acid, whereas others were extremely insensitive requiring in excess of 100 nA to be excited. This range of sensitivities was seen throughout all cortical layers. 3. Glutamate was most effective in uncovering new receptive fields or in enhancing preexisting somatic responses in the bottom of layer II/III and in layer IV. Receptive fields uncovered by glutamate had properties comparable to receptive fields observed without drugs. Overall, glutamate enhanced the ability of afferent inputs to drive 39% of the neurons tested. 4. In 61% of the cells tested with glutamate there was no evidence of somatic input even during excitation with glutamate. Of 50 cells displaying receptive fields, only two were enlarged by treatment with glutamate. For 36 other cells receptive fields of normal dimensions were uncovered during glutamate administration. 5. Bicuculline uncovered more somatic inputs than either glutamate or ACh, leaving only 37% of 86 cells tested without evidence of excitatory inputs from the skin. Bicuculline produced an average receptive-field enlargement of 8.7 times in 11 of 56 cells tested. This drug acted uniformly throughout the cortical layers. 6. ACh excited 36.9% of the 360 cells tested. Those excited tended to be located in laminae Vb and VIb. The effects of ACh on afferent response properties could not be predicted from its ability to excite a cell. The magnitude of the response to 100 nA of ACh varied with the laminar position of the cell being tested, being weakest in layer II/III and greatest in layer Vb. 7. Overall, 34.2% of 263 cells showed changes in afferent drive during ACh treatment. ACh enhanced the responses to somatic stimulation most frequently in laminae IV and V. 8. Of the 90 neurons tested for long-term effects, 27% displayed effects of ACh that significantly outlasted the duration of the ACh administration. In 18% of these, changes lasted for greater than 5 min, sometimes remaining altered for the duration of the time that the cell was studied. These long-term changes in excitability were generally produced by administration of ACh during the time that the cell was excited by glutamate or by somatic stimulation.

Acetylcholine↗

PubMed1988

Classification of muscarinic responses in hippocampus in terms of receptor subtypes and second-messenger systems: electrophysiological studies in vitro.

The hippocampal slice preparation was used to classify cholinergic effects in terms of muscarinic receptor subtypes (M1 or M2) and biochemical effector systems linked to these effects in CA1 pyramidal cells. Based on the action of the M1 antagonist pirenzepine and the M2 antagonist gallamine, the muscarinic-induced membrane depolarization and blockade of the afterhyperpolarization appear to result from activation of an M1 receptor, while the cholinergic depression of the EPSP and the blockade of a potassium current termed the M-current appears to involve the activation of an M2 receptor. All of the muscarinic actions could be observed in pertussis toxin-treated hippocampi, suggesting that a pertussis toxin-sensitive G-protein is not involved in these actions. Cholinergic agents that are weak agonists of phosphoinositide (PI) turnover are fully effective in all of the muscarinic actions except the blockade of the M-current on which they had little agonist activity and actually blocked the action of full agonists. These results strongly suggest that the blockade of the M-current may involve stimulation of PI turnover. In addition, we show that the blockade of the M-current is mimicked by intracellular application of inositol trisphosphate. Our results do not show any obvious relationship between the muscarinic receptor subtypes and the biochemical effector systems.

Animals↗

PubMed1987

Modulation of the excitability of septohippocampal terminals in the rat: relation to neuronal discharge rate.

The excitability of the axonal terminals of medial septal neurons projecting to the dentate gyrus has been studied in the anesthetized rat under various experimental conditions: spontaneous or drug-induced variations in neuronal soma discharge rate, conditioning stimulation of afferent pathways (perforant path, commissural pathway, fimbria-fornix). It has been observed that terminals excitability is inversely correlated to the level of neuronal ongoing activity. These effects were observed on virtually all septal neurons projecting to the dentate gyrus. Since about one half of the septohippocampal neurons are likely to be cholinergic, it follows that such a phenomenon is not transmitter specific.

Action Potentials↗

PubMed1987

Septo-hippocampal neurons: altered properties in the aged rat.

The septo-hippocampal pathway is one of the best characterized cholinergic pathways of the mammalian central nervous system. It is very likely that this pathway is involved in the pathophysiology of dementia of the Alzheimer's type and perhaps of normal aging also. The properties of the septo-hippocampal neurons identified by their antidromic response to the electrical stimulation of the fimbria-fornix were altered in aged (27 months) rats as compared to young (2-3 months) controls: their pattern of spontaneous activity (including the frequency of occurrence of a rhythmically bursting activity) and their axonal conduction velocity were altered. The intensity of these changes was dependent on the presence of pituitary tumor which developed spontaneously in about 1/3 of the animals. These results provide direct evidence of the involvement of septo-hippocampal neurons in the aging process.

Action Potentials↗

PubMed1986

Modifications in the cortical regional distribution of choline acetyltransferase, somatostatin and somatostatin binding sites in the normal rat and following lesion of the nucleus basalis.

The regional distribution of choline acetyltransferase activity, somatostatin levels and 125I-CGP 23996 (a somatostatin agonist analog) specific binding sites in 10 separate zones of the cerebral cortex was analyzed. The study was performed in normal rats as well as 15 days after unilateral excitotoxic lesion of the nucleus basalis. A significant correlation was found in the controls between the regional distribution of choline acetyltransferase activity and somatostatin concentrations, both most highly concentrated in the piriform and entorhinal cortex. In contrast, the regional density of 125I-CGP 23996 binding sites correlated neither with choline acetyltransferase activity nor with somatostatin levels. Unilateral lesions of the basal forebrain decreased choline acetyltransferase activity in the frontal and parietal cortex, while 125I-CGP 23996 binding decreased in frontal and occipital regions. No decrease in somatostatin content was observed. The results suggest that, in rats, cortical somatostatin receptors could be associated with cholinergic afferents from the nucleus basalis in the frontal cortex only.

Animals↗

PubMed1986

Septo-hippocampal neurons in the rat: further study of their physiological and pharmacological properties.

Medial septal-nucleus of the diagonal band of Broca area (MS-nDBB) neurons, identified by their antidromic response to the electrical stimulation of the fimbria and/or hippocampus, were studied in the rat under various conditions of anesthesia. These septo-hippocampal neurons (SHNs) were classified into 4 groups on the basis of: (i) their antidromic latency; and (ii) the presence or absence of a rhythmically bursting pattern of spontaneous discharge. The rhythmically bursting activity (43.5% of the SHNs) was highly dependent on the anesthetic conditions. The groups of SHNs differed in their mean conduction velocity and rate of spontaneous activity. In contrast, irrespective of their classification in a particular group, the large majority of the SHNs could be excited by the iontophoretic application of cholinergic agonists. Beside the SHNs, two other populations of MS-nDBB neurons could be identified by electrical antidromic stimulation: neurons projecting to the amygdala (Am) and neurons projecting through the medial forebrain bundle (MFB). Half of the MS-nDBB neurons projecting to Am were also antidromically driven from the fimbria. The axonal branch projecting to Am had a slower conduction velocity than that projecting to hippocampus. In contrast MS-nDBB neurons projecting through the MFB were never antidromically driven from the fimbria, although they received orthodromic inputs. They had a slower conduction velocity than the other groups of MS-nDBB neurons.

Amygdala↗

PubMed1986

Comparison of septo-hippocampal with basalo-cortical projection neurons in the rat: an electrophysiological approach.

The electrophysiological properties of septo-hippocampal (SHNs) and basalo-cortical neurons (BCNs) identified by antidromic stimulation were compared in rats anesthetized with urethane. SHNs and BCNs had comparable conduction velocities (about 2-3 m/s) and relatively high spontaneous firing rates (about 20 impulses/s). In contrast, they differed in their pattern of spontaneous discharge as studied by generating inter-spike interval histograms. Many BCNs had a regular pattern of discharge. Among SHNs, about 40% had a spontaneous rhythmically bursting pattern of discharge, whereas the remaining 60% had a more or less irregular pattern. These results suggest that SHNs represent a more heterogeneous neuronal population than BCNs, and that central cholinergic neurons involved in different systems might also have different properties.

Action Potentials↗

PubMed1986

Basal forebrain neurons projecting to the rat frontoparietal cortex: electrophysiological and pharmacological properties.

Neurons located in the ventromedial globus pallidus (nucleus basalis) and substantia innominata, that were antidromically driven by electrical stimulation of the frontoparietal cortex, were recorded in the urethane anesthetized rat. The basalocortical neurons (BCNs) were antidromically driven with latencies of 1.1-13.5 ms, giving conduction velocities of 0.6-6.8 m/s. Many BCNs had regular patterns of spontaneous discharge (mean spontaneous activity: 20 impulses/s). Most BCNs were not responsive to non-noxious peripheral somatic stimulation. BCNs were readily excited by the iontophoretic application of glutamate and strongly inhibited by GABA. Eighty-five percent of the BCNs could be excited by acetylcholine. They could also be excited by cholinergic agonists. Muscarinic agonists excited a higher proportion of BCNs than nicotinic agonists. Excitatory responses to acetylcholine, carbachol and muscarinic agonists were abolished by atropine.

Acetylcholine↗

PubMed1986

Septohippocampal neurons after intraventricular AF64A administration in rats: an electrophysiological study.

The putative cholinergic neurotoxin, ethylcholine aziridinium ion (AF64A), was injected bilaterally into the cerebral ventricles of male rats. The properties of the medial septum-nucleus of the diagonal band of Broca's area (MS-nDBB) neurons were studied 4 to 6 or 19 to 23 days following injections. The spontaneous activity of those neurons was higher in the injected animals, but their responses to glutamate and cholinergic agonists were not modified. The proportion of orthodromic responses elicited by fimbria-fornix stimulation in MS-nDBB neurons was unchanged. In contrast, the proportion of septohippocampal neurons (SHNs) identified by the antidromic stimulation of the fimbria-fornix was smaller in pretreated animals and their mean antidromic latency was shorter. These results suggest that intracerebroventricular administration of the neurotoxin AF64A is followed by changes in the properties of MS-nDBB neurons and specifically by the disappearance of a subpopulation of SHNs.

Animals↗

PubMed1986

[Excitability of septo-hippocampal axon terminals: changes as a function of the level of neuronal activity].

The septo-hippocampal terminals were electrically stimulated at the level of the gyrus dentatus in urethane anesthetized rats and antidromic responses were recorded in the medial septum. The excitability of the terminals was assessed by the threshold of terminal antidromic activation. An increase in the discharge frequency of the septal neurons following a microiontophoretic application of glutamate to their soma induced an increase in the antidromic activation threshold, i.e. a decrease in excitability of the terminals. An application of GABA which inhibited septal neuronal activity, induced a decrease in the antidromic activation threshold, i.e. an increase in the terminal excitability of septo-hippocampal neurons. These results are discussed in the light of the presynaptic autoreceptor hypothesis.

Acetylcholine↗

PubMed1985

Septohippocampal neurons in the rat: an in vivo intracellular study.

In vivo intracellular recordings were obtained from septohippocampal neurons identified by their antidromic response to electrical stimulation of the fimbria in rats anesthetized with pentobarbital or urethane. Beside the antidromic response, fimbria stimulation evoked a short-latency depolarizing potential (EPSP) followed by an hyperpolarizing potential which reversed polarity when recorded with KCl-filled electrodes. This IPSP is therefore likely to be chloride-dependent. It was followed by a long-lasting (80-250 ms) depolarizing potential often associated with a burst of spikes. Septohippocampal neurons therefore receive an inhibitory, chloride-mediated, input which itself triggers a long-lasting excitatory event. These results are consistent with extracellular observations. Their significance in the septohippocampal circuitry is discussed.

Animals↗

PubMed1985

Effects of TRH, cyclo-(His-Pro) and (3-Me-His2)TRH on identified septohippocampal neurons in the rat.

Neurons located in the medial septum-nucleus of the diagonal band of Broca (vertical limb) and antidromically activated by electrical stimulation of the fimbria were recorded in urethane anesthetized rats. Forty-three percent of these septohippocampal neurons (SHNs) were excited by the iontophoretic application of thyrotropin-releasing hormone (TRH). Rhythmically bursting SHNs were more often excited (63%) by TRH than the non-bursting SHNs (35%). The majority of the TRH-sensitive SHNs could also be excited by cholinergic agonists. TRH-induced excitations were not abolished by the simultaneous application of atropine. Potentiation by TRH of acetylcholine, carbachol or glutamate-induced excitations of SHNs were rarely observed. Cyclo (His-Pro) and (3-Me-His2)-TRH were observed to have similar, although less dramatic, effects. These results demonstrate that the SHNs, which are the neurons of origin of the septohippocampal pathway, are readily excited by TRH.

Acetylcholine↗