Contextual signals in visual cortex:How sounds, state, and task setting shape how we see

What we see is not always what we get. Even though the light that hits the retina might convey the same images, how visual information is processed and what we eventually do with it depend on many contextual factors. In this thesis, we show in a series of experiments how the sensory processing of the same visual input in the visual cortex of mice is affected by our internal state, movements, other senses and any task we are performing. We found that recurrent activity originating within higher visual areas modulates activity in the primary visual cortex (V1) and selectivity amplifies weak compared to strong sensory-evoked responses. Second, visual stimuli evoked similar early activity in V1, but later activity strongly depended on whether mice were trained to report the visual stimuli, and on the specific task. Specifically, adding a second modality to the task demands extended the temporal window during which V1 was causally involved in visual perception. Third, we report that not only visual stimuli but also sounds led to strong responses in V1, composed of distinct auditory-related and motor-related activity. Finally, we studied the role of Posterior Parietal Cortex in an audiovisual change detection task. Despite extensive single-neuron and population-level encoding of task-relevant visual and auditory stimuli, as well as upcoming behavioral responses, optogenetic inactivation did not affect task performance. Whereas these contextual factors have previously been studied in isolation, we obtain a more integrated understanding of how factors beyond visual information determine what we actually see

Binding of small interfering RNA molecules is crucial for RNA interference suppressor activity of rice hoja blanca virus NS3 in plants

The NS3 protein of rice hoja blanca tenuivirus represents a viral suppressor of RNAi that sequesters small interfering (si)RNAs in vitro. To determine whether this siRNA binding property is the critical determinant for the suppressor activity of NS3, an alanine point mutational analysis was performed and the resulting mutant proteins were tested for both siRNA binding ability and RNAi suppressor activity in plants. Alanine substitutions of lysine residues at position 173-175 resulted in mutant proteins that lost both their affinity for siRNAs and their RNAi suppressor activity in planta. This indicates that siRNA binding of NS3 is indeed essential for the suppressor function of NS3 and that residues at position 173-175 are involved in the siRNA binding and suppressor activit

Programming of adult metabolic health:the roles of dietary cholesterol and microbiota in early life

The obesity prevalence has increased in adults and kids. This is worrying because early life obesity is associated with metabolic diseases in early and adult life. Recent data indicated that changes in the early nutritional and microbial environment impact the development of chronic disease (obesity, diabetes, cardiovascular disease) at adult age. The research in this thesis provides valuable insights into how early life factors such as cholesterol supply via the breast milk or diet and microbiota presence during defined time-frames in early life of mice contribute to physiology and metabolism later in life. Cholesterol is an important building block for our cell membranes, hormones and bile acids (BA). Our research shows that breast milk cholesterol levels are stable despite up to 5-fold increases in maternal blood cholesterol levels due to high cholesterol diet. This suggests a possible important role for a stable cholesterol supply to the offspring during lactation. Indeed, our research shows that the lactation period, but not the post-lactation period seems a critical time-frame for long-term cholesterol metabolism. Intestinal microbiota composition has an impact on the interaction between host and environment at all stages of our lives. Surprisingly, our data imply that microbiota (absence) in early life does not critically affect adult metabolism. Also, fecal transplantation in germ-free mice with a donor of the same or opposing sex did not affect bile acid composition on the long term. However, qualitative differences in microbiota composition in humans and mice may influence metabolism and the risk to develop chronic diseases

Glocal Place, Lived Space: Everyday life in a Tibetan Buddhist monastery for Nuns in Northern India

Dahles, H. [Promotor

Characterizing Linkage Disequilibrium in Pig Populations

Knowledge of the extent and range of linkage disequilibrium (LD), defined as non-random association of alleles at two or more loci, in animal populations is extremely valuable in localizing genes affecting quantitative traits, identifying chromosomal regions under selection, studying population history, and characterizing/managing genetic resources and diversity. Two commonly used LD measures, r(2) and D', and their permutation based adjustments, were evaluated using genotypes of more than 6,000 pigs from six commercial lines (two terminal sire lines and four maternal lines) at ~4,500 autosomal SNPs (single nucleotide polymorphisms). The results indicated that permutation only partially removed the dependency of D' on allele frequency and that r(2) is a considerably more robust LD measure. The maximum r(2) was derived as a function of allele frequency. Using the same genotype dataset, the extent of LD in these pig populations was estimated for all possible syntenic SNP pairs using r(2) and the ratio of r(2) over its theoretical maximum. As expected, the extent of LD highest for SNP pairs was found in tightest linkage and decreased as their map distance increased. The level of LD found in these pig populations appears to be lower than previously implied in several other studies using microsatellite genotype data. For all pairs of SNPs approximately 3 centiMorgan (cM) apart, the average r(2) was equal to 0.1. Based on the average population-wise LD found in these six commercial pig lines, we recommend a spacing of 0.1 to 1 cM for a whole genome association study in pig populations