Publications du Neurocentre Magendie

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IF du Neurocentre

682 publications

* equal contribution
Les IF indiqués ont été collectés par le Web of Sciences en Juin 2018

11/1989 | Pharmacol Biochem Behav   IF 2.5
Septal alpha-noradrenergic antagonism in vivo blocks the testing-induced
Marighetto A, Durkin T, Toumane A, Lebrun C, Jaffard R

In order to test the hypothesis that alpha-noradrenergic receptors in the septum

09/1989 | Behav Neural Biol
The durations of hippocampal and cortical cholinergic activation induced by
Toumane A, Durkin T, Marighetto A, Jaffard R

Sodium-dependent high-affinity choline uptake velocities in P2 fractions of the

1989 | Arch Gerontol Geriatr Suppl   IF 2.2
Experimental dissociation of memory systems in mice: behavioral and neurochemical
Jaffard R, Durkin T, Toumane A, Marighetto A, Lebrun C

Evidence for different types of memory in mice may lead to development of animal

10/1988 | Behav Brain Res   IF 3.2
Differential hippocampal and cortical cholinergic activation during the
Toumane A, Durkin T, Marighetto A, Galey D, Jaffard R

Possible differentiation of the intervention of cholinergic septohippocampal and

Male rats received a dopaminergic implant aimed either at the nucleus accumbens or the ventral tegmental area (VTA) following 6-hydroxydopamine lesion of their mesocorticolimbic dopaminergic system. Exposure to electrical footshock stress 6 months later markedly activated the mesocorticolimbic neurons in control animals as shown by the increase of dihydroxyphenylacetic acid (DOPAC) levels both in the nucleus accumbens and the VTA. However, no stress-induced activation was seen for the grafted neurons, irrespective of the area of implantation. These results indicate the lack of reinnervation and modulation of the grafted dopaminergic neurons by one of the important afferent systems regulating the activity of endogenous mesencephalic dopaminergic neurons.

The aim of the study was to obtain a description of some aspects of the development of intracerebral dopaminergic grafts, namely, the time course of the glial reaction and its relation to cell division on one hand, and the development of graft-originated innervation and its dependence on adequate matching of the implanted neurons and target site on the other hand. Cell suspensions obtained from the mesencephalon or hypothalamus of embryonic day (ED) 14 rat embryos were implanted into the striatum or lateral hypothalamus of adult rats following the destruction of the nigrostriatal system of the hosts. Animals were sacrificed at different postimplantation times, and the development of the graft was followed by immunohistochemistry by using antisera directed against tyrosine hydroxylase (TH) or glial fibrillary acidic protein (GFA). Furthermore, the existence of cell division at various times following implantation was examined by performing autoradiography on immunostained sections after prior intraventricular administration of 3H-thymidine to the host. The first stage of the development of intracerebral grafts was characterized by the existence of intense cell division within the grafted tissue, lasting about 2 weeks, and also in the host tissue surrounding the graft, lasting only about 6 days. The cell division in the host tissue was paralleled by the existence of a strong glial reaction which, however, did not extend into the graft itself. Glial reaction in the host tissue gradually decreased at later times and disappeared by 4 weeks postimplantation without leaving behind a noticeable glial scar. The graft itself was, however, transiently filled with a population of reactive astroglial cells between 3 and 6 weeks postimplantation. Within grafts of mesencephalic tissue located in the striatum TH-positive neurons were distributed evenly at short times postimplantation (2-6 days). At later time a compartmentation could be observed, with TH-positive neurons being aligned along the graft-host interface or clustered within the graft itself. Innervation of the host tissue by TH-positive fibers increased between 1 and 6 weeks postimplantation. On the other hand, no compartmentation and reinnervation of surrounding host tissue was observed for intrahypothalamic grafts of mesencephalic tissue or intrastriatal grafts of hypothalamic tissue. This last observation indicates that adequate matching of implanted neurons and target tissue plays an important role in the development of intracerebral dopaminergic grafts.

Local lesion of the dopaminergic (DA) terminals of the nucleus accumbens have been described to reproduce part of the behavioral deficits evoked by the lesion of the whole mesocorticolimbic DA system. The most straightforward interpretation of these results would be that the DA innervation of the nucleus accumbens is necessary for and critically involved in the normal performance of the given behaviors. However, while giving some indication as to the necessity of the integrity of this DA innervation for normal behaviors, such an approach cannot reveal whether the presence of the DA innervation of other mesocorticolimbic areas (e.g. amygdala, septum, etc.) is also required. In order to approach this question, the behavioral effects of DA grafts implanted into the nucleus accumbens of rats were evaluated following two different 6-hydroxydopamine-induced lesions: a lesion restricted to the anterior DA field (DA terminals of the nucleus accumbens and to a lesser degree the frontal cortex and anteromedial striatum) or a lesion of the whole mesocorticolimbic DA system. The latter lesion induces a disappearance of the DA innervation of the nucleus accumbens as well as the amygdala, septum, etc. Both kinds of lesions led to locomotor hypoactivity, loss of locomotor activation by amphetamine, increased locomotor stimulation to apomorphine, decrease of exploratory activity and loss of hoarding behavior. These deficits were not seen in grafted animals bearing a local lesion of the DA innervation of this structure. For some of these recoveries, however, a pharmacological stimulation of the grafted neurons was required to reveal the effect of the graft. In the case of the total lesion of the mesocorticolimbic DA system, only locomotor dysfunctions were compensated by the intra-accumbens DA implants, while the other deficits remained intact, irrespective of a stimulation of the graft. These results indicate that the re-establishment of the DA innervation of the nucleus accumbens is a sufficient condition for the compensation of locomotor deficits, irrespective of the presence of the DA terminals in more posterior limbic structures, while for deficits of more complex behaviors the simultaneous presence of posterior DA innervations is also required. This latter requirement suggests the existence of some cooperativity between the different central DA terminal areas for the normal performance of behaviors.

Cortical cells obtained from rat embryos (ED14 to ED20) were implanted in various regions of rat brain and the presence of tyrosine hydroxylase (TH)-, neuropeptide Y (NPY)- and Met-enkephalin (ENK)-immunoreactive neurons within the grafts were tested using an immunohistochemical approach. TH-like immunoreactive (TH-LI) neurons were present within the implants obtained from ED14, but not ED18 or ED20, embryos up to 10 months post-implantation and their presence was not dependent on the age of the host (adult or neonate) at the time of implantation. Furthermore, the density of such cells varied with the site of implantation, being the highest in the dorsomedial corner of the striatum. This distorted development seems to affect also other cell populations, such as NPY-LI neurons which could be observed within the implants in a density much higher than that found in the normal cortex and which presented generally a rather immature morphology. It has been described that the rat cortex contains TH-LI neurons only during a limited period of development. The survival of such neurons within intracerebral grafts of cortical tissue indicates that their disappearance during normal cortical development is dependent upon environmental cues. The survival of TH-LI cells in grafts implanted to neonatal hosts suggests that these cues are not some humoral factors appearing postnatally. On the other hand, the present observations are compatible with several other hypothesis concerning the nature of such cues: humoral factors present during the late embryonic period, signals dependent on neuronal connectivities (input and/or outputs) established during embryonic or postnatal life.(ABSTRACT TRUNCATED AT 250 WORDS)

1988 | Exp Brain Res   IF 1.8
Intrastriatal dopaminergic grafts restore inhibitory control over striatal cholinergic neurons.
Herman JP, Lupp A, Abrous N, Le Moal M, Hertting G, Jackisch R

The aim of the study was to examine the influence of intrastriatal dopaminergic grafts on the functioning of striatal cholinergic neurons using an in vitro superfusion method. Rats bearing unilateral 6-hydroxydopamine lesion of the nigrostriatal dopaminergic system received a cell suspension obtained from ED 14 rat embryonic mesencephali which was injected into the denervated striatum. Lesioned animals displayed an ipsilateral rotation in response to amphetamine (5 mg/kg i.p.). This rotational response disappeared following grafting and there was even a significant contralateral rotation in response to the drug. Apomorphine (0.1 mg/kg s.c.) induced a contralateral rotation following the lesion. This latter response was attenuated in the grafted group. Three months after grafting 350 microns thick slices were prepared from striata from the control and experimental sides of lesioned and graft-bearing animals. The slices were preincubated either with 3H-dopamine (10(-7) M) or 3H-choline (10(-7) M) and then superfused with an oxygenated Krebs-Ringer solution. Stimulation with electrical pulses following preincubation with 3H-dopamine elicited a marked increase of tritium outflow from control slices. Stimulation-evoked overflow was of similar magnitude from slices from striata containing the graft, while it was much reduced in slices from lesioned striata. Amphetamine markedly potentiated the effect of electrical stimulation in slices obtained from control and graft-containing striata. Nomifensine (a dopamine uptake blocker) led to a significant decrease of the overflow of 3H-acetylcholine evoked by electrical stimulation from control striatal slices. This inhibition was antagonized by domperidone, a D2 dopamine receptor blocker, a finding which indicates that the action of nomifensine was indeed due to a potentiation of the action of endogenous dopamine released by the electrical stimulation. A similar, although somewhat attenuated, action of nomifensine and domperidone was observed for striatal slices containing the graft. Amphetamine inhibited the stimulation evoked overflow of 3H-acetylcholine in a dose-dependent manner from striatal slices obtained both from the intact and experimental sides of graft-bearing animals, while it had no action on slices from denervated striata. Finally, the dose-response curve for the inhibition of 3H-acetylcholine release by apomorphine was significantly shifted to the left for slices from the lesioned striata as compared with control slices. This leftward shift was totally abolished in the slices from the graft-containing striatum.(ABSTRACT TRUNCATED AT 400 WORDS)