A computational model of prefrontal and striatal interactions in perceptual category learning.

Work on multiple-system theories of cognition mostly focused on the systems themselves, while limited work has been devoted to understanding the interactions between systems. Generally, multiple-system theories include a model-based decision system supported by the prefrontal cortex and a model-free decision system supported by the striatum. Here we propose a neurobiological model to describe the interactions between model-based and model-free decision systems in category learning. The proposed model used spiking neurons to simulate activity of the hyperdirect pathway of the basal ganglia. The hyperdirect pathway acts as a gate for the response signal from the model-free system located in the striatum. We propose that the model-free system's response is inhibited when the model-based system is in control of the response. The new model was used to simulate published data from young adults, people with Parkinson's disease, and aged-matched older adults. The simulation results further suggest that system-switching ability may be related to individual differences in executive function. A new behavioral experiment tested this model prediction. The results show that an updating score predicts the ability to switch system in a categorization task. The article concludes with new model predictions and implications of the results for research on system interactions.

Effect of edaravone in diabetes mellitus-induced nephropathy in rats.

Edaravone, a synthetic-free radical scavenger, has been reported to reduce ischemia-reperfusion-induced renal injury by improving tubular cell function, and lowering serum creatinine and renal vascular resistance. The present study investigated the effect of edaravone in diabetes mellitus-induced nephropathy in rats. A single administration of streptozotocin (STZ, 55 mg/kg, i.p.) was employed to induce diabetes mellitus in rats. The STZ-administered diabetic rats were allowed for 10 weeks to develop nephropathy. Mean body weight, lipid alteration, renal functional and histopathology were analysed. Diabetic rats developed nephropathy as evidenced by a significant increase in serum creatinine and urea, and marked renal histopathological abnormalities like glomerulosclerosis and tubular cell degeneration. The kidney weight to body weight ratio was increased. Moreover, diabetic rats showed lipid alteration as evidenced by a signifi cant increase in serum triglycerides and decrease in serum high-density lipoproteins. Edaravone (10 mg/kg, i.p., last 4-weeks) treatment markedly prevented the development of nephropathy in diabetic rats by reducing serum creatinine and urea and preventing renal structural abnormalities. In addition, its treatment, without significantly altering the elevated glucose level in diabetic rats, prevented diabetes mellitus-induced lipid alteration by reducing serum triglycerides and increasing serum high-density lipoproteins. Interestingly, the renoprotective effect of edaravone was comparable to that of lisinopril (5 mg/kg, p.o, 4 weeks, standard drug). Edaravone prevented renal structural and functional abnormalities and lipid alteration associated with experimental diabetes mellitus. Edaravone has a potential to prevent nephropathy without showing an anti-diabetic action, implicating its direct renoprotection in diabetic rats.