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A M Thierry

Publications and source records attributed to A M Thierry.

At least 37 records · Page 2Linked to original sources

Indirect nucleus accumbens input to the prefrontal cortex via the substantia nigra pars reticulata: a combined anatomical and electrophysiological study in the rat.

The nucleus accumbens is a major component of the ventral striatum through which most of the limbic affiliated cortical areas gain access to the basal ganglia circuitry. In this study, the organization of the pathways linking the nucleus accumbens to the thalamus, via the substantia nigra pars reticulata, was examined in the rat using anatomical and electrophysiological methods. Use of anterograde and retrograde transport of wheatgerm agglutinin conjugated to horseradish peroxidase has established that the core of the nucleus accumbens innervates a dorsal region of the substantia nigra pars reticulata which projects to subfields of the mediodorsal and ventral medial thalamic nuclei. These subfields consist of the rostral pole of the mediodorsal nucleus with the exception of its central segment and a region of the ventral medial nucleus, medial to the mammillothalamic tract. Confirming the existence of a nucleus accumbens nigrothalamic link, we have observed that electrical or chemical stimulation of the nucleus accumbens induces an inhibition of the spontaneous discharges of the nigral cells which project to the mediodorsal and ventral medial thalamic nuclei. Finally, the cortical projections of the thalamic subfields involved in the nucleus accumbens nigrothalamic circuit were determined using the anterograde and retrograde axonal transport of wheatgerm agglutinin conjugated with horseradish peroxidase. These subfields innervate mainly the prelimbic and to a lesser degree the orbital areas of the prefrontal cortex. The present data show that the substantia nigra pars reticulata is a major link between the core of the nucleus accumbens and the prefrontal cortex and provide further evidence for the concept of a parallel architecture in the basal ganglia thalamocortical circuits of the ventral striatum.

Action Potentials↗

Inhibitory effects of ventral tegmental area stimulation on the activity of prefrontal cortical neurons: evidence for the involvement of both dopaminergic and GABAergic components.

The medial prefrontal cortex of the rat receives dopamine and non-dopaminergic projections from the ventral tegmental area. Both electrical stimulation of the ventral tegmental area and local application of dopamine induce an inhibition of the spontaneous activity of most prefrontal cortical neurons, including efferent neurons. In the present study, the techniques of extracellular recording and microiontophoresis were used in anesthetized rats in order to determine whether these dopamine- and ventral tegmental area-induced inhibitory responses involve GABAergic components. Prefrontal cortex output neurons were identified by antidromic activation from subcortical structures. The inhibitory responses evoked by the local application of dopamine were blocked by the iontophoretic application of the D2 antagonist sulpiride, and the GABAA antagonist bicuculline in 89 and 57% of the cases, respectively. In addition, sulpiride and bicuculline abolished the inhibition induced by ventral tegmental area stimulation in 54 and 51% of the prefrontal cortical cells tested, respectively. The implication of a non-dopaminergic mesocortical system in the ventral tegmental area-induced inhibition was further analysed using rats pre-treated with alpha-methylparatyrosine to deplete dopamine stores. The proportion of prefrontal cortical cells inhibited by ventral tegmental area stimulation was markedly reduced (39%) in alpha-methylparatyrosine-treated rats, when compared to controls (86%). Remaining ventral tegmental area-induced inhibition was no longer affected by sulpiride, but in all cases blocked by the local microiontophoretic application of bicuculline. The present results suggest that: (1) the dopamine-induced inhibition of prefrontal cortex neurons could involve cortical GABAergic interneurones; (2) the non-dopaminergic mesocortical system exerts also an inhibitory influence on prefrontal cortical cells and appears to be GABAergic.

Animals↗

Anesthetic properties of riluzole (54274 RP), a new inhibitor of glutamate neurotransmission.

It has been suggested that some anesthetic agents could exert their hypnotic/anesthetic effects by selectively blocking receptors involved in the central excitatory neurotransmission mediated by glutamate. In the present study, we analyzed whether riluzole (54274 RP), a novel compound that inhibits both the release and some postsynaptic effects of glutamate in some brain structures, has anesthetic properties in rats. For this purpose, we investigated whether 1) riluzole administered intraperitoneally (ip) at doses ranging from 2.5 to 45 mg/kg induces loss of righting reflex (LRR); 2) riluzole (2.5 and 5 mg/kg) prolongs sleep-times induced by either ketamine (30 or 80 mg/kg ip) or thiopental (25 or 35 mg/kg ip); 3) a 5-mg/kg subanesthetic riluzole dose affects the minimum alveolar concentration of halothane (MACh). Onset of drug action was defined as the period of time from the ip injection to LRR. Sleep-time was considered the period of time from LRR to restoration of righting reflex. Riluzole at doses greater than 15 mg/kg was able to induce LRR (riluzole dose for which LRR was achieved in 50% of the rats [ED50 = 25.6 mg/kg]). A positive correlation was found between the dose of riluzole and sleep-time (r = 0.92, P less than 0.001). A 5-mg/kg (but not 2.5-mg/kg) riluzole dose significantly prolonged sleep-times induced by both ketamine (30 and 80 mg/kg) and thiopental (25 but not 35 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthetics↗

The novel 5-HT2 receptor antagonist, RP 62203, selectively blocks serotoninergic but not dopaminergic-induced inhibition in the rat prefrontal cortex.

The influence of the novel 5-hydroxytryptamine2 (5-HT2) receptor antagonist, RP 62203, on serotoninergic neurotransmission was investigated using an in vivo electrophysiological technique. For this purpose, the ability of RP 62203 (1-3 mg/kg i.p.) to block the inhibitory responses of prefrontal cortical neurons induced by electrical stimulation of the median raphe nucleus was examined in anesthetized rats. In addition, the effects of RP 62203 on the dopaminergic inhibitory responses induced in the prefrontal cortex by stimulation of the ventral tegmental area and on the enhancement of these responses by lysergic acid diethylamide (LSD, a 5-HT2 receptor agonist, 30 or 60 micrograms/kg i.p.), were analyzed. RP 62203 blocked the inhibition induced by median raphe nucleus stimulation in a dose-dependent and reversible fashion. In contrast, RP 62203 failed to affect the inhibitory responses induced in prefrontal cortical cells by stimulation of the ventral tegmental area. However, the enhancement by LSD of the inhibition induced by stimulation of the ventral tegmental area in the prefrontal cortex was blocked by RP 62203. These results demonstrate that RP 62203 selectively blocks serotoninergic, but not dopaminergic, neurotransmission in the prefrontal cortex.

Animals↗

Inhibitory influence of the mesocortical dopaminergic neurons on their target cells: electrophysiological and pharmacological characterization.

Both dopaminergic (DA) and noradrenergic (NA) systems exert an inhibitory influence on the activity of prefrontal cortical neurons (PFC). As NA-containing fibers run close to the dorsal ventral tegmental area (VTA), electrical stimulation of the VTA might coactivate both DA and NA systems. In the present study extracellular recordings and microiontophoresis were used in anesthetized rats to analyze first whether the inhibitory cortical responses to VTA stimulation and DA application were mediated by DA or adrenergic receptors. Inhibitory responses elicited by DA application or VTA stimulation were observed in PFC output neurons identified by antidromic activation from subcortical structures. Both types of inhibitory effects were reversed by the DA antagonist sulpiride, but not by the adrenergic antagonists prazosin (alpha-1), yohimbine (alpha-2) or propranolol (beta). NA and the beta agonist isoproterenol inhibited the activity of PFC cells and these effects were antagonized by propranolol, but neither by prazosin and yohimbine nor by the DA antagonist sulpiride. Thus, the inhibitory influence of the mesocortical DA system in the PFC involves DA, but not NA, recognition sites. The DA receptor subtype mediating the inhibitory effects of VTA stimulation and DA application in the PFC was analyzed further. VTA- and DA-evoked inhibitory responses were antagonized by the D2 selective antagonists (-)-sulpiride, LUR 2366 and RIV 2093, but not by the D1 selective antagonist SCH23390. In addition, the DA-induced inhibitory response was mimicked by the selective D2 agonist LY 171555 but not by the selective D1 agonist SKF 38393. Surprisingly, haloperidol, which is also a potent D2 antagonist, failed to consistently block DA- and VTA-induced inhibitory effects. The present results indicate that the inhibition of PFC cells by mesocortical DA neurons is mediated via a subtype of DA receptors which is particularly sensitive to benzamides.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Inhibition of spontaneous and evoked unit activity in the rat medial prefrontal cortex by mesencephalic raphe nuclei.

The rat medial prefrontal cortex (PFC) receives a serotoninergic (5-HT) innervation which originates from the mesencephalic raphe nuclei. In the present study we determined the influence of the 5-HT ascending systems on the spontaneous and evoked activity of PFC neurons in anesthetized rats. Stimulation of the dorsal (DRN) and of the median raphe (MRN) nuclei inhibited the spontaneous activity of 35.0% and 52.8% of the PFC cells tested (mean duration of the inhibition: 75.5 and 82.2 ms, respectively). These inhibitory responses are likely mediated by the 5-HT-containing neurons since they were decreased markedly following selective destruction of ascending 5-HT pathways induced by local injections of 5,7-dihydroxytryptamine. Moreover, the inhibitory effect of MRN stimulation could be blocked by systemic administration of the 5-HT2 receptor antagonists: ketanserin and ritanserin. The effects of MRN stimulation on two types of evoked responses were studied. The excitatory responses of PFC neurons induced by the stimulation of the mediodorsal nucleus of the thalamus (MD) were inhibited by MRN stimulation applied before that of MD. Similarly, the activation of PFC cells induced by a noxious tail pinch was suppressed by a concomitant stimulation of the MRN. These results indicate that 5-HT neurons exert an inhibitory control on spontaneous or evoked activity in the rat PFC.

5,7-Dihydroxytryptamine↗

Long-term potentiation in the prefrontal cortex following stimulation of the hippocampal CA1/subicular region.

We have examined single cell activity and field potentials in the prelimbic area of the prefrontal cortex of the rat to electrical stimulation of the CA1/subicular region of the temporal hippocampus. Excitatory unit responses were found in 50 out of 120 neurons recorded in the prelimbic area. Paired-pulse facilitation was found for both single cell responses and field potentials. High-frequency, tetanic stimulation of the temporal hippocampus produced a significant and persistent potentiation of prelimbic field potentials. The evidence suggests that the direct pathway from the temporal hippocampus to the prelimbic area of the prefrontal cortex in the rat is excitatory and can undergo long-term potentiation (LTP).

Animals↗

Selectivity of the hippocampal projection to the prelimbic area of the prefrontal cortex in the rat.

Afferent connections of the medial and lateral prefrontal cortex of the rat arising from the hippocampal formation were investigated using iontophoretic application of the fluorescent tracer, Fluoro-gold. Our results demonstrate that the projection which originates in the temporal part of the CA1 hippocampal field and in the prosubiculum is restricted to the prelimbic area of the prefrontal cortex.

Animals↗

Effect of noxious tail pinch on the discharge rate of mesocortical and mesolimbic dopamine neurons: selective activation of the mesocortical system.

The effects of noxious tail pinch on the activity of mesocortical and mesolimbic dopamine (DA) neurons located in the ventromedial mesencephalic tegmentum were analyzed in ketamine-anesthetized rats. The great majority of mesocortical DA neurons responded to tail pinch, either by an excitation (65%), or by an inhibition (25%). In contrast, most DA neurons projecting either to the nucleus accumbens or the septum remained unaffected. These results demonstrate that noxious tail pinch selectively influences the firing rate of mesocortical DA neurons.

Action Potentials↗

Nondopaminergic prefrontocortical efferent fibers modulate D1 receptor denervation supersensitivity in specific regions of the rat striatum.

A unilateral injection of 6-OHDA (6 microgram/1.5 microliter) was made into the fields of Forel in order to estimate the effects of the destruction of ascending dopaminergic (DA) pathways on the denervation supersensitivity of DA D1 receptors in the rat striatum. DA-sensitive adenylate cyclase activity was markedly enhanced in the anteromedian part of the striatum 3 weeks after the lesion (+68%) and remained elevated for several weeks thereafter (+36%). A different response occurred in the laterodorsal striatum, where the increase in DA-sensitive adenylate cyclase activity was less pronounced after 3 weeks (+40%) and no longer present after 7 weeks. Estimations of catecholamine levels indicated that the lesion made destroyed not only nigrostriatal DA neurons but other ascending catecholaminergic fibers projecting into the cerebral cortex as well. In addition, retrograde transport experiments made with wheat germ agglutinin coupled to horseradish peroxidase indicated that the anteromedian part of the striatum, but not the laterodorsal one, receives both an ipsi- and contralateral cortical projection originating in the prefrontocortical DA field. When the destruction by 6-OHDA of this contralateral DA innervation was combined to the unilateral lesion of the fields of Forel, the increase in DA-sensitive adenylate cyclase activity in each striatal area 3 or 7 weeks postlesion was prevented. This effect was due to DA denervation of the prefrontal cortex since striatal D1 denervation supersensitivity was still observed when contralateral ascending noradrenergic fibers were selectively destroyed by a 6-OHDA lesion made laterally to the pedunculus cerebellaris superior. These results suggest that, by controlling the activity of corticostriatal neurons, the mesocorticoprefrontal DA neurons exert a permissive role on the development of D1-receptor denervation supersensitivity in specific areas of the striatum.

Adenylyl Cyclases↗

Differential effects of ascending neurons containing dopamine and noradrenaline in the control of spontaneous activity and of evoked responses in the rat prefrontal cortex.

The medial prefrontal cortex receives converging projections from the mediodorsal thalamic nucleus, dopaminergic cells from the ventral tegmental area dn noradrenergic cells from the locus coeruleus. Stimulation of the ventral tegmental area inhibits the spontaneous activity of prefrontal cortical neurons and blocks the excitatory response evoked by stimulation of the mediodorsal thalamic nucleus (10 Hz). The aim of the present study was to compare the influence of dopaminergic and noradrenergic afferents on the spontaneous and evoked activity of medial prefrontal cortical neurons. In ketamine-anaesthetized rats, repetitive stimulation (20 Hz, 10 s) of the locus coeruleus produced a long-lasting post-stimulus inhibition (mean duration: 45 s) of the spontaneous activity of 56% of the tested cells. This effect was decreased markedly following selective destruction of the ascending noradrenergic pathways (local 6-hydroxy-dopamine injection) or depletion of cortical catecholamines by alpha-methyl-para-tyrosine pretreatment, suggesting that these inhibitory responses are mediated by noradrenergic neurons. The excitatory response to mediodorsal thalamus nucleus stimulation (10 Hz) could still be evoked during the post-stimulus inhibitory period induced by locus coeruleus stimulation (20 Hz, 10 s) resulting in the enhancement of signal-to-noise ratio. On the other hand, a population of prefrontal cortex neurons (26%) was found to be reproducibly activated by noxious tail pinch. This evoked response was still present during the post-stimulus inhibitory period induced by locus coeruleus stimulation but was completely suppressed during stimulation of the ventral tegmental area (10 Hz). In conclusion, these results indicate that the dopaminergic and noradrenergic systems exert a completely distinct control of information transfer in the medial prefrontal cortex.

Animals↗

Interhemispheric and subcortical collaterals of medial prefrontal cortical neurons in the rat.

Efferent neurons of rat medial prefrontal cortex, projecting to subcortical structures and contralateral homotypical areas, were analyzed using anatomical and electrophysiological methods. Anterograde labelling with radioactive amino acids demonstrated the pathways of these efferents in the rostral part of the brain; terminal fields in contralateral cortical areas and localization of fibers projecting subcortically were particularly examined. The laminar location of cells projecting to the contralateral prefrontal cortex or through the striatum was investigated by means of the retrograde transport of wheat germ agglutinin-horseradish peroxidase (WGA-HRP) injected in these two structures. Cells innervating the contralateral prefrontal cortex were distributed in layers II-III and V, whereas injection of WGA-HRP in the striatum labelled cells in layer V. The antidromic activation technique was used to identify the cortical neurons which innervate the ipsilateral and contralateral subcortical structures as well as contralateral homotypical cortical areas. Among 743 recorded neurons, 282 neurons were antidromically driven from at least one of the stimulated sites (e.g. right striatum (RS), left striatum (LS), and contralateral prefrontal cortex (L-Cx]. The mean conduction velocities were 0.6 m/s and 0.8 m/s for subcortical and cortical efferents, respectively. The reciprocal collision test provided evidence for the existence of branched axons for 35% of the antidromically activated cells. All the possible branching patterns were found. The results of this study thus demonstrate the existence of single neocortical neurons that send axon collaterals to contralateral cortex and subcortical structures.

Action Potentials↗