Knockout of lysosomal enzyme-targeting gene causes abnormalities in mouse pup isolation calls

Humans lacking a working copy of the GNPTAB gene suffer from the metabolic disease Mucolipidosis type II (MLII). MLII symptoms include mental retardation, skeletal deformities and cartilage defects as well as a speech delay with most subjects unable to utter single words (Otomo et al., 2009; Cathey et al., 2010; Leroy et al., 2012). Here we asked whether mice lacking a copy of Gnptab gene exhibited vocal abnormities. We recorded ultrasonic vocalizations from 5 to 8 day old mice separated from their mother and littermates. Although Gnptab(−/−) pups emitted a similar number of calls, several features of the calls were different from their wild type littermates. Gnptab(−/−) mice showed a decrease in the length of calls, an increase in the intra-bout pause duration, significantly fewer pitch jumps with smaller mean size, and an increase in the number of isolated calls. In addition, Gnptab(−/−) mice vocalizations had less power, particularly in the higher frequencies. Gnptab(+/−) mouse vocalizations did not appear to be affected. We then attempted to classify these recordings using these features to determine the genotype of the animal. We were able to correctly identify 87% of the recordings as either Gnptab(−/−) or Gnptab(+/+) pup, significantly better than chance, demonstrating that genotype is a strong predictor of vocalization phenotype. These data show that deletion of genes in the lysosomal enzyme targeting pathway affect mouse pup isolation calls

Changes in the firing patterns in neurons of the sensorimotor striatum during learning : what changes and why

Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Brain and Cognitive Sciences, 2010.Cataloged from PDF version of thesis.Includes bibliographical references.The basal ganglia, and specifically the sensorimotor (dorsolateral) striatum, have been implicated in stimulus-response learning. Here, I analyze the role the striatum plays in learning. We recorded from neurons of the sensorimotor striatum as rats learn, are over-trained, are extinguished, and are re-trained on a discriminative T-maze task. In this T-maze a gate was lowered immediately after an auditory click and the rats were allowed to proceed down the long arm of the maze. Mid-run, one of two tones was played. Rats had to choose to turn down either the left or right arm of the T-maze based on which tone was played. We discovered that population neural activity becomes restructured during learning and overtraining to emphasize the beginning and end of each trial. We also created a short-term memory version of the T-maze task by moving the location of the tone cue in order to determine if this affects the strength of the restructuring seen in the firing patterns of the striatum as learning progressed. Lastly, we examined the relationship the training induced pattern had to learning the tone-turn association and to other things that changed systematically throughout learning, such as speed./ by Terra D. Barnes.Ph.D

Insights into the Molecular Mechanisms of the Anti-Atherogenic Actions of Flavonoids in Normal and Obese Mice

Obesity is a major and independent risk factor for cardiovascular disease and it is strongly associated with the development of dyslipidemia, insulin resistance and type 2 diabetes. Flavonoids, a diverse group of polyphenol compounds of plant origin widely distributed in human diet, have been reported to have numerous health benefits, although the mechanisms underlying these effects have remained obscure. We analyzed the effects of chronic dietary supplementation with flavonoids extracted from cranberry (FLS) in normal and obese C57/BL6 mice compared to mice maintained on the same diets lacking FLS. Obese mice supplemented with flavonoids showed an amelioration of insulin resistance and plasma lipid profile, and a reduction of visceral fat mass. We provide evidence that the adiponectin-AMPK pathway is the main mediator of the improvement of these metabolic disorders. In contrast, the reduced plasma atherogenic cholesterol observed in normal mice under FLS seems to be due to a downregulation of the hepatic cholesterol synthesis pathway. Overall, we demonstrate for the first time that the molecular mechanisms underlying the beneficial effects of flavonoids are determined by the metabolic state

On the mechanisms governing gas penetration into a tokamak plasma during a massive gas injection

A new 1D radial fluid code, IMAGINE, is used to simulate the penetration of gas into a tokamak plasma during a massive gas injection (MGI). The main result is that the gas is in general strongly braked as it reaches the plasma, due to mechanisms related to charge exchange and (to a smaller extent) recombination. As a result, only a fraction of the gas penetrates into the plasma. Also, a shock wave is created in the gas which propagates away from the plasma, braking and compressing the incoming gas. Simulation results are quantitatively consistent, at least in terms of orders of magnitude, with experimental data for a D 2 MGI into a JET Ohmic plasma. Simulations of MGI into the background plasma surrounding a runaway electron beam show that if the background electron density is too high, the gas may not penetrate, suggesting a possible explanation for the recent results of Reux et al in JET (2015 Nucl. Fusion 55 093013)