Proefschrift Universiteit Maastricht. / Auteursnaam op omslag: Sylvia Jans. Met bibligr., lit. opg. - Met een samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met bibliogr., lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Maastricht. / Met lit. opg. - Met samenvatting in het Nederlands.

Proefschrift Universiteit Maastricht. / Met lit. opg. - Met een samenvatting in het Nederlands.

Thèse--Sc. nat.--Paris 6, 1971. / Bibliogr.

Le kisspeptine (kp) est un peptide, dérivé du gène kiss-1, jouant un rôle majeur dans le contrôle central de la fonction de reproduction en régulant la sécrétion du GnRH chez l’adulte mais également au cours du développement. Les neurones exprimant kiss-1 sont situés dans la région rostrale périventriculaire du 3ème ventricule (RP3V) et le noyau arqué (ARC). L’expression de kiss-1 est hautement régulée par les stéroides sexuels, positivement dans RP3V et négativement dans ARC. Ces deux populations de neurones à kp semblent avoir des rôles différents. Les neurones à kp du RP3V seraient impliqués dans la genèse du pic préovulatoire et ceux de l’ARC dans la régulation de la sécrétion pulsatile de GnRH.L’objectif de la thèse était de déterminer la période de neurogenèse des neurones à kp ainsi que les variations de l’expression de kiss-1 et de kp dans ces deux régions au cours des différentes phases du développement chez le rat mâle et femelle.Nos résultats ont permis de cibler les périodes clés de l’ontogenèse des neurones à kp en montrant 1) que les neurones à kp de l’ARC naissent sur une période étendue à partir du jour embryonnaire (E)12,5; 2) l’existence d’une sous- expression péri-natale du kp dans l’ARC indépendante du sexe; 3) la mise en place, en période néonatale, de différences sexuelles dans les niveaux d’expression et la distribution neuroanatomique du kp; 4) l’existence de régulations péri-pubertaires de kp, dépendantes du sexe et de la région ; 5) la présence de fibres à kp dans des régions hypothalamiques suggère un rôle de kp au-delà de la fonction de reproduction. / Kisspeptin (kp) is a neuropeptide, derived from the kiss-1 gene, which plays a key role in the central control of reproduction by regulating GnRH secretion in adult but also during development. Cells which express kiss-1 are localized in two distincts hypothalamic regions: the rostral peri-ventricular third ventricule area (RP3V) and the arcuate nucleus (ARC). Kiss-1 expression is highly regulated by sex steroids: positively in the RP3V and negatively in the ARC. RP3V kp neurons have been implicated in the pre-ovulatory GnRH surge whereas ARC kp neurons may predominantly act on GnRH secretion pulsatility. The aim of this PhD work was to determine the neurogenesis period of kp neurons and changes of kiss-1 and kp expression in both regions during different stages of development in rats. Our results highlight key periods of kp neurons ontogenesis and show that: 1) ARC kp neurons are born during an extended embryonic neurogenesis period starting at embryonic day (E) 12,5; 2) a sex independent down-regulation of kp occurs during peri-natal period; 3) sex difference in the expression level and neuroanatomique distribution of kp establishes during neo-natal period; 4) kp was regulated during peri-pubertal period in sex and region dependant manner; 5) kp-ir fibers are detected throughout the septo-hypothalamic continuum suggesting that kp could be implicated in other functions than reproductive function.

According to Piaget and Bartlett, learning involves both assimilation of new memories into networks of preexisting knowledge and alteration of existing networks to accommodate new information into existing schemas. Recent evidence suggests that the hippocampus integrates related memories into schemas that link representations of separately acquired experiences. In this thesis, I first review models for how memories of individual experiences become consolidated into the structure of world knowledge. Disruption of consolidated memories can occur during related learning, which suggests that consolidation of new information is the reconsolidation of related memories. The accepted role of the hippocampus during memory consolidation and reconsolidation suggests that it is also involved in modifying appropriate schemas during learning. To study schema development, I trained rats to retrieve rewards at different loci on a maze while recording hippocampal calls. About a quarter of cells were active at multiple goal sites, though the ensemble as a whole distinguished goal loci from one another. When new goals were introduced, cells that had been active at old goal locations began firing at the new locations. This initial generalization decreased in the days after learning. Learning also caused changes in firing patterns at well-learned goal locations. These results suggest that learning was supported by modification of an active schema of spatially related reward loci. In another experiment, I extended these findings to explore a schema of object and place associations. Ensemble activity was influenced by a hierarchy of task dimensions which included: experimental context, rat's spatial location, the reward potential and the identity of sampled objects. As rats learned about new objects, the cells that had previously fired for particular object-place conjunctions generalized their firing patterns to new conjunctions that similarly predicted reward. In both experiments, I observed highly structured representations for a set of related experiences. This organization of hippocampal activity counters key assumptions in standard models of hippocampal function that predict relative independence between memory traces. Instead, these findings reveal neural mechanisms for how the hippocampus develops a relational organization of memories that could support novel, inferential judgments between indirectly related events.

The literature relating to the ontogeny of the opioid system and to the toxic effects of lead in both man and animals with particular reference to neurochemical and behavioural toxicity of lead is reviewed. The effects of perinatal lead exposure on the development of several aspects of opioid function has been studied using a dosing model of lead (as the acetate) in the maternal drinking water from conception until postnatal day 14 or 21. This model of low level perinatal lead exposure in rats had no toxic effects on growth and produced blood lead levels close to the safety limits set for human exposure and similar to those that have been recorded in some children. The ontogeny of morphine antinociception using the tail immersion test and ketocyclazocine in the paw pressure test was studied in 10,21 and 30 day old rats. Perinatal lead exposure decreased the antinociceptive activity of both morphine and ketocyclazocine in 10 day old rats. Recovery of morphine antinociception occured by 21 days and ketocyclazocine antinociception by 30 days. Radioligand binding studies with [3H]DAGO were used to study the ontogeny of u-opioid receptors in 10,21 and 30 day old rats. Perinatal lead exposure was without effect on equilibrium dissociation constant or maximal binding capacity. Radioligand binding studies with [[3]H] DPDPE were used to study the ontogeny of 6 -opioid receptors in rats between 15 and 50 days. The affinity of the 6-opioid binding site for [[3]H] DPDPE was reduced by perinatal lead exposure but without accompanying changes in binding capacity. This effect of lead on s-opioid receptors was persistant and was observed in rats aged 15-50 days. Basal plasma corticosterone levels (measured fluorimetrically) were elevated by perinatal lead exposure in 45 and 60 day old rats but not in 30 day old rats. In addition the modulatory effect of morphine on stress induced elevations of corticosterone levels was also affected by lead exposure. A reduced effect of morphine was seen in 30 day old animals whilst an increased effect was seen in 60 day old animals. Locomotor activity (measured by photocell detection) of 10,21 and 30 day old rats was recorded over 1 hour during the dark phase of the light/dark cycle. Exploratory locomotor activity was reduced in lead exposed animals at postnatal day 10 and the hypolocomotor effect of morphine was also increased in 10 day old lead exposed animals. The opioid system is particularly sensitive to perinatal low level lead exposure and this is manifested in several aspects of physiological function. Possible mechanisms by which lead affects the development of the opioid system are discussed.

The significance of vocal communication in subterranean rodents was confirmed. In this study I tested whether vocalization of the Mashona mole-rats (Fukomys darlingi) differs individually and what information about signaller are these mole-rats able to obtain using only acoustic cues.

No description available.