Developmental dynamics of neurotensin binding sites in the human hypothalamus during the first postnatal year.

The aim of the present study was to determine a detailed mapping of neurotensin (NT) in the human hypothalamus, during the first postnatal year using an in vitro quantitative autoradiography technique and the selective radioligand monoiodo-Tyr3-NT. Ten human postmortem hypothalami obtained from control neonates and infants (aged from 2 h to 1 year of postnatal age) were used. The biochemical kinetics of the binding in all obtained in this study revealed that the binding affinity constants were of high affinity (in the nanomolar range) and did not differ significantly between all cases investigated. Furthermore, competition experiments show insensitivity to levocabastine and were in favor of the presence of the high affinity site of NT receptor. Autoradiographic distribution showed that NT binding sites were widely distributed throughout the rostrocaudal extent of the hypothalamus. However, the distribution of NT binding sites was not homogenous and regional variations exist. In general, the highest densities were mainly present in the anterior hypothalamic level, particularly in the preoptic area. High NT binding site densities are also present at the mediobasal hypothalamic level, particularly in the paraventricular, parafornical, and dorsomedial nuclei. At the posterior level, low to very low densities could be observed in all the mammillary complex subdivisions, as well as the posterior hypothalamic area. Although this topographical distribution is almost identical during the postnatal period analyzed, age-related variations exist in discrete structures of the hypothalamus. The densities were higher in neonates/less aged infants than older infants in preoptic area (medial and lateral parts). The developmental profile is characterized by a progressive decrease from the neonate period to 1 year of postnatal age with a tendency to reach adult levels. On the other hand, the low levels of NT binding sites observed in posterior hypothalamus did not vary during the first postnatal year. They contrast in that with the very high levels we reported previously in adult. In conclusion, the present study demonstrates the occurrence of high NT binding sites density in various structures in many regions in the human neonate/infant hypothalamus, involved in the control of neuroendocrine and/or neurovegetative functions.

An autoradiographic study of neurotensin receptors in the human hypothalamus.

The aim of the present investigation was to determine a detailed mapping of neurotensin (NT) in the human hypothalamus, the brain region involved in neuroendocrine control. For this, we investigated the presence and the distribution of neurotensin binding sites in the human hypothalamus, using an in vitro quantitative autoradiography technique and the selective radioligand monoiodo-Tyr3-neurotensin (2000Ci/mM). This study was performed on nine adult human postmortem hypothalami. We first determined the biochemical kinetics of the binding and found that binding affinity constants were of high affinity and do not differ significantly between all cases investigated. Our analysis of the autoradiographic distribution shows that NT binding sites are widely distributed throughout the rostrocaudal extent of the hypothalamus. However, the distribution of NT binding sites is not homogenous and regional variations exist. In general, the highest densities are mainly present in the anterior hypothalamic level, particularly in the preoptic region and the anterior boarding limit (i.e. the diagonal band of Broca). Important NT binding site densities are also present at the mediobasal hypothalamic level, particularly in the paraventricular, parafornical and dorsomedial nuclei. At the posterior level, relatively moderate densities could be observed in the mammillary complex subdivisions, apart from the supramammillary nucleus and the posterior hypothalamic area. In conclusion, the present study demonstrates the occurrence of high concentrations of NT binding sites in various structures in many regions in the human adult hypothalamus, involved in the control of neuroendocrine and/or neurovegetative functions.

Contribution of corticosterone to cued versus contextual fear in rats.

Several studies have suggested a positive relationship between circulating corticosterone levels and contextual conditioning. However, a positive relationship between circulating corticosterone levels and cued conditioning has also been reported. This study further investigates the relationship between corticosterone and fear conditioning by modulating the predictive value of contextual and discrete tone cues in separate groups of rats. In a first experiment in which training parameters were chosen to induce strong conditioning (five foot-shocks), we used a correlational approach and investigated whether post-training corticosterone levels were related to subsequent expression of contextual and/or tone fear. In a second experiment, in which training parameters were chosen to induce lower conditioning (one and two foot-shocks), we investigated whether a post-training corticosterone injection enhanced the consolidation of contextual and/or tone conditioning. In the first experiment, the highest post-training corticosterone levels were obtained in rats trained with paired tones and shocks. Post-training corticosterone levels tended to be positively correlated with freezing scores during the tone-fear test and were negatively correlated with freezing scores during training although not during the context-fear test. In the second experiment, a post-training injection of corticosterone (3mg/kg) had no effect on subsequent freezing to contextual cues and to a tone that did not predict shock, whereas it was efficient in increasing fear conditioned to a predictive tone. Globally, these results suggest that the predictive value of the conditioned stimulus may be the main determinant of the facilitatory action of acutely enhanced corticosterone in fear conditioning.

Contextual and serial discriminations: a new learning paradigm to assess simultaneously the effects of acute stress on retrieval of flexible or stable information in mice.

The present study was aimed at simultaneously determining on the same subject, the effects of stress on retrieval of flexible (contextual or temporal) or stable (spatial) information. Three behavioral paradigms carried out in a four-hole board were designed as follows: (1) Simple Discrimination (SD), in which mice learned a single discrimination; (2) Contextual and Serial Discriminations (CSD), in which mice learned two successive discriminations on two different internal contexts; (3) Spatial Serial Discriminations (SSD), in which mice learned two successive discriminations on an identical internal context. The stressor (three inescapable electric footshocks) was delivered 5 min before retention, occurring 5 min or 24 h after acquisition. Results showed that this stressor increased plasmatic corticosterone levels and fear reactivity in an elevated-plus-maze, as compared with nonstressed mice. The stressor reversed the normal pattern of retrieval observed in nonstressed controls in the CSD task, this effect being context dependent, as it was not observed in the SSD task. Overall, our study shows that stress affected the retrieval of flexible and old information, but spared the retrieval of stable or recent ones. Therefore, these behavioral paradigms allow us to study simultaneously, on the same animal, the effects of stress on distinct forms of memory retrieval.