Fractionating choice: A study on reward discrimination, preference, and relative valuation in the rat (Rattus norvegicus).

Choice behavior combines discrimination between distinctive outcomes, preference for specific outcomes and relative valuation of comparable outcomes. Previous work has focused on 1 component (i.e., preference) disregarding other influential processes that might provide a more complete understanding. Animal models of choice have been explored primarily utilizing extensive training, limited freedom for multiple decisions and sparse behavioral measures constrained to a single phase of motivated action. The present study used a paradigm that combines different elements of previous methods with the goal to distinguish among components of choice and explore how well components match predictions based on risk-sensitive foraging strategies. In order to analyze discrimination and relative valuation, it was necessary to have an option that shifted and an option that remained constant. Shifting outcomes among weeks included a change in single-option outcome (0 to 1 to 2 pellets) or a change in mixed-option outcome (0 or 5 to 0 or 3 to 0 or 1 pellets). Constant outcomes among weeks were also mixed-option (0 or 3 pellets) or single-option (1 pellet). Shifting single-option outcomes among weeks led to better discrimination, more robust preference and significant incentive contrast effects for the alternative outcome. Shifting multioptions altered choice components and led to dissociations among discrimination, preference, and reduced contrast effects. During extinction, all components were impacted with the greatest deficits during the shifting mixed-option outcome sessions. Results suggest choice behavior can be optimized for 1 component but suboptimal for others depending upon the complexity of alterations in outcome value between options. (PsycINFO Database Record

Role of procoagulant lipids in human prothrombin activation. 1. Prothrombin activation by factor X(a) in the absence of factor V(a) and in the absence and presence of membranes.

Activation of prothrombin by factor X(a) requires proteolysis of two bonds and is commonly assumed to occur via by two parallel, sequential pathways. Hydrolysis of Arg(322)-Ile(323) produces meizothrombin (MzII(a)) as an intermediate, while hydrolysis of Arg(273)-Thr(274) produces prethrombin 2-fragment 1.2 (Pre2-F1.2). Activation by human factor X(a) of human prothrombin was examined in the absence of factor V(a) and in the absence and presence of bovine phosphatidylserine (PS)/palmitoyloleoylphosphatidylcholine (25:75) membranes. Four sets of data were collected: fluorescence of an active site probe (DAPA) was sensitive to thrombin, MzII(a), and Pre2-F1.2; a synthetic substrate (S-2238) detected thrombin or MzII(a) active site formation; and SDS-PAGE detected both intermediates and thrombin. The fluorescence data provided an internal check on the active site and SDS-PAGE measurements. Kinetic constants for conversion of intermediates to thrombin were measured directly in the absence of membranes. Both MzII(a) and Pre2-F1.2 were consumed rapidly in the presence of membranes, so kinetic constants for these reactions had to be estimated as adjustable parameters by fitting three data sets (thrombin and MzII(a) active site formation and Pre2 appearance) simultaneously to the parallel-sequential model. In the absence of membranes, this model successfully described the data and yielded a rate constant, 44 M(-1) s(-1), for the rate of MzII(a) formation. By contrast, the parallel-sequential model could not describe prothrombin activation in the presence of optimal concentrations of PS-containing membranes without assuming that a pathway existed for converting prothrombin directly to thrombin without release from the membrane-enzyme complex. The data suggest that PS membranes (1) regulate factor X(a), (2) alter the substrate specificity of factor X(a) to favor the meizothrombin intermediate, and (3) "channel" intermediate (MzII(a) or Pre2-F1.2) back to the active site of factor X(a) for rapid conversion to thrombin.