Temporal and Spatial Control of Germ-Plasm RNAs

SummaryIn many species, germ cells form in a specialized germ plasm, which contains localized maternal RNAs [1–5]. In the absence of active transcription in early germ cells, these maternal RNAs encode germ-cell components with critical functions in germ-cell specification, migration, and development [6, 7]. For several RNAs, localization has been correlated with release from translational repression, suggesting an important regulatory function linked to localization [3, 4, 8, 9]. To address the role of RNA localization and translational control more systematically, we assembled a comprehensive set of RNAs that are localized to polar granules, the characteristic germ-plasm organelles. We find that the 3′-untranslated regions (UTRs) of all RNAs tested control RNA localization and instruct distinct temporal patterns of translation of the localized RNAs. We demonstrate necessity for translational timing by swapping the 3′UTR of polar granule component (pgc), which controls translation in germ cells, with that of nanos, which is translated earlier. Translational activation of pgc is concurrent with extension of its poly(A) tail length but appears largely independent of the Drosophila CPEB homolog ORB. Our results demonstrate a role for 3′UTR mediated translational regulation in fine-tuning the temporal expression of localized RNA, and this may provide a paradigm for other RNAs that are found enriched at distinct cellular locations such as the leading edge of fibroblasts or the neuronal synapse

The amygdala in value-guided decision making

Thesis: Ph. D. in Neuroscience, Massachusetts Institute of Technology, Department of Brain and Cognitive Sciences, 2017.Cataloged from PDF version of thesis.Includes bibliographical references.The amygdala is a structure well known for its role in fear and reward learning, but how these mechanisms are used for decision-making is not well understood. Decision-making involves the rapid updating of cue associations as well as the encoding of a value currency, both processes in which the amygdala has been implicated. In this thesis I develop a strategy to study value-guided decision making in rodents using an olfactory binary choice task. Using a logistic regression model, I show that the value of expected rewards is a strong influence on choice, and can bias perceptual decisions. In addition, I show that decisions are influenced by events in the near past, and a specific bias towards correct choices in the near past can be detected using this analysis. Using genetic targeting of a sub-population of amygdala neurons, I show that this population is required for the rapid learning of an olfactory decision making task. Using in-vivo calcium imaging of this population I show that these neurons are active during the inter-trial interval and modulated by choice history, suggesting a mechanism by which choice history can influence current decisions.by Kean Jaime-Bustamante.Ph. D. in Neuroscienc