Standardized and reproducible measurement of decision-making in mice

Progress in science requires standardized assays whose results can be readily shared, compared, and reproduced across laboratories. Reproducibility, however, has been a concern in neuroscience, particularly for measurements of mouse behavior. Here we show that a standardized task to probe decision-making in mice produces reproducible results across multiple laboratories. We designed a task for head-fixed mice that combines established assays of perceptual and value-based decision making, and we standardized training protocol and experimental hardware, software, and procedures. We trained 140 mice across seven laboratories in three countries, and we collected 5 million mouse choices into a publicly available database. Learning speed was variable across mice and laboratories, but once training was complete there were no significant differences in behavior across laboratories. Mice in different laboratories adopted similar reliance on visual stimuli, on past successes and failures, and on estimates of stimulus prior probability to guide their choices. These results reveal that a complex mouse behavior can be successfully reproduced across multiple laboratories. They establish a standard for reproducible rodent behavior, and provide an unprecedented dataset and open-access tools to study decision-making in mice. More generally, they indicate a path towards achieving reproducibility in neuroscience through collaborative open-science approaches

Cellulose utilization by Clostridium thermocellum: Bioenergetics and hydrolysis product assimilation

The bioenergetics of cellulose utilization by Clostridium thermocellum was investigated. Cell yield and maintenance parameters, [Formula: see text] g cell/mol ATP and m = 3.27 mmol ATP/g cell per hour, were obtained from cellobiose-grown chemostats, and it was shown that one ATP is required per glucan transported. Experimentally determined values for [Formula: see text] (ATP from phosphorolytic β-glucan cleavage minus ATP for substrate transport, mol ATP/mol hexose) from chemostats fed β-glucans with degree of polymerization (DP) 2-6 agreed well with the predicted value of (n-1)/n (n = mean cellodextrin DP assimilated). A mean [Formula: see text] value of 0.52 ± 0.06 was calculated for cellulose-grown chemostat cultures, corresponding to n = 4.20 ± 0.46. Determination of intracellular β-glucan radioactivity resulting from (14)C-labeled substrates showed that uptake is different for cellulose and cellobiose (G2). For (14)C-cellobiose, radioactivity was greatest for G2; substantially smaller but measurable for G1, G3, and G4; undetectable for G5 and G6; and n was ≈2. For (14)C-cellulose, radioactivity was greatest for G5; lower but substantial for G6, G2, and G1; very low for G3 and G4; and n was ≈4. These results indicate that: (i) C. thermocellum hydrolyzes cellulose by a different mode of action from the classical mechanism involving solubilization by cellobiohydrolase; (ii) bioenergetic benefits specific to growth on cellulose are realized, resulting from the efficiency of oligosaccharide uptake combined with intracellular phosphorolytic cleavage of β-glucosidic bonds; and (iii) these benefits exceed the bioenergetic cost of cellulase synthesis, supporting the feasibility of anaerobic biotechnological processing of cellulosic biomass without added saccharolytic enzymes