Spatial learning deficits in mice with a targeted glucocorticoid receptor gene disruption

Previous studies in rats using the Morris water maze suggested that the processing of spatial information is modulated by corticosteroid hormones through mineralocorticoid and glucocorticoid receptors in the hippocampus. Mineralocorticoid receptors appear to be involved in the modulation of explorative behaviour, while additional activation of glucocorticoid receptors facilitates the storage of information. In the present study we used the water maze task to examine spatial learning and memory in mice homozygous and heterozygous for a targeted disruption of the glucocorticoid receptor gene. Compared with wild-type controls, homozygous and heterozygous mice were impaired in the processing of spatial but not visual information. Homozygous mutants performed variably during training, without specific platform-directed search strategies. The spatial learning disability was partly compensated for by increased motor activity. The deficits were indicative of a dysfunction of glucocorticoid receptors as well as of mineralocorticoid receptors. Although the heterozygous mice performed similarly to wild-type mice with respect to latency to find the platform, their strategy was more similar to that of the homozygous mice. Glucocorticoid receptor-related long-term spatial memory was impaired. The increased behavioural reactivity of the heterozygous mice in the open field points to a more prominent mineralocorticoid receptor-mediated function. The findings indicate that (i) the glucocorticoid receptor is of critical importance for the control of spatial behavioural functions, and (ii) mineralocorticoid receptor-mediated effects on this behaviour require interaction with functional glucocorticoid receptors. Until the development of site-specific, inducible glucocorticoid receptor mutants, glucocorticoid receptor-knockout mice present the only animal model for the study of corticosteroid-mediated effects in the complete absence of a functional receptor.     

THE EARLY TO "MIDDLE" CRETACEOUS LITHOSTRATIGRAPHY OF THE CENTRAL NORTH SEA (UK SECTOR)

A revised lithostratigraphical framework of the Early to "Middle" Cretaceous strata of the Central North Sea (UK sector) derived from the rigorous examination of more than 100 commercial boreholes is presented. previously published frameworks have tended toward oversimplification of the Early to "Middle" Cretaceous, as the interval was considered initially to be of minor importance with regard to prospectivity. However_: there is a general feeling in the industry that the Early to "Middle" Cretaceous is prospective. particularly with regard to subtle stratigraphical traps like the Kilda/Bosun and Scapa fields. It is inevitable that as more attention, due to hydrocarbon exploration, is paid to an interval that the stratigraphical models used progress from the simplistic to the complex. The framework presented here is the result of a pragmatic approach in that it is based upon the integration of previously published schemes. with the erection of new units derived from new analyses and interpretation. The complete lithostratigraphical framework is defined. explained and discussed with reference to borehole examples in the Central North Sea .     

Transfer of a discrimination by pigeons (Columba livia) between pictured locations and the represented environments.

In Exp 1, pigeons (Columba livia) were trained in a successive slide presentation procedure to discriminate between pictures of 2 ends of a room and then trained to find food in the actual room. A congruent-transfer (CT) group learned the spatial discrimination more quickly than an incongruent-transfer (IT) group. In Exp 2's replication we used a simultaneous slide presentation procedure and added a control group. The IT group required significantly more trials than the CT or control groups. In Exp 3, order of the training conditions was reversed. CT and IT conditions had no effect on the speed of acquisition of the discrimination. This indicates that pigeons acquire a representation of spatial locations from pictures, which can then direct behavior, but the direction of transfer observed was unidirectional. This suggests that a discrimination between spatial locations may not be accurately represented in pictorial form. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Modification of the calcium and calmodulin sensitivity of the type I adenylyl cyclase by mutagenesis of its calmodulin binding domain

The type I adenylyl cyclase is directly stimulated by Ca2+ and calmodulin in vitro, and the enzyme is also stimulated by increases in intracellular Ca2+ in vivo. Ca2+ stimulation of the enzyme in vivo may be due to direct interactions of the enzyme with Ca2+ and calmodulin or to an indirect mechanism involving stimulation of the enzyme by Ca(2+)-activated protein kinases. In this study, we have made several point mutations within the calmodulin binding domain to determine if the Ca2+ sensitivity of the enzyme can be modified by mutagenesis. The catalytic activities of the mutant enzymes were comparable to wild type type I adenylyl cyclase. Substitution of Cys-507 with Ser-507 did not have significant effects on the calmodulin or Ca2+ sensitivity of the enzyme. However, replacement of Lys-504 with Asp caused a 4-fold decrease in sensitivity to Ca2+. Ca2+ and calmodulin stimulation were abolished by substitution of Phe-503 with Arg-503. Stimulation of type I adenylyl cyclase activity in vivo by intracellular Ca2+ was also greatly diminished with the Arg-503 mutant indicating that Ca2+ stimulation of the enzyme in vivo is due primarily to direct interactions with calmodulin and Ca2+. These data demonstrate that the Ca2+ sensitivity of this enzyme can be modulated by point mutagenesis within the putative calmodulin binding domain and indicate that the enzyme can be directly regulated by Ca2+ and calmodulin in vivo.     

Surface electronic structure of rare earth metals

Angle-resolved UV photoemission has been used to investigate the electronic structure of the (0001) surfaces of scandium, yttrium, praseodymium and gadolinium. Off-normal emission spectra were recorded with high angular resolution, enabling detailed mapping of the dispersion of valence band features. Yttrium and gadolinium show similar results to published data from Ho(0001), suggesting minimal 4f influence in the lanthanide bandstructures. Differences seen on praseodymium and scandium may be due to 4f derived states and surface states respectively.