2,508 research outputs found

    Neurotransmitters and receptors in the motion vision pathway of Drosophila

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    The fruit fly Drosophila melanogaster is one of the most popular model organisms being used in the life sciences. Due to its small number of neurons compared to other vertebrate species and its genetic access, it has also proven itself to be an optimal model organism for neuroscience. Especially, the field of systems neuroscience has made quick advances in its study of neural circuits of the fly brain underlying sensory perception such as olfaction and vision, as well as complex behaviors such as mating, learning, and memory. The motion vision pathway in the optic lobe of the fruit fly is a prominent example of a computation-performing neural circuit that researchers have been trying to understand for decades. While the wiring of the main circuit elements has been described via EM-reconstructions and their response properties have been characterized comprehensively, the molecular mechanisms of direction-selectivity still remain elusive. However, subcellular components such as neurotransmitter receptors and ion channels are important since they define the sign and the temporal dynamics of synaptic connections within a circuit. Hence, the main focus of my thesis was the investigation of neurotransmitter receptors in the primary motion sensing T4/T5 neurons of the fly brain, including the development of required genetic tools. First, we developed a protocol for super-resolution STED imaging in Drosophila brain slices which allowed us to resolve fine dendritic structures of individual T4/T5 neurons deep inside the brain (Manuscript 1). Second, we used the glutamate sensor iGluSnFR to characterize the temporal dynamics of the three glutamatergic cell types of the motion vision pathway L1, Mi9 and LPi (Manuscript 2). We validated the usability of iGluSnFR for measuring glutamate signaling in adult Drosophila brains and found that responses recorded with iGluSnFR are faster than GCaMP signals of the same cells. In Manuscript 3, we developed new genetic strategies for conditional protein labeling. Specifically, we introduced FlpTag, a tool for endogenous, conditional labeling of proteins by means of a flippase-dependent, invertible GFP cassette integrated in the endogenous gene locus. Using these methods, we explored the subcellular localizations of neurotransmitter receptors for glutamate, GABA, acetylcholine and voltage-gated ion channels in T4/T5 neurons in Drosophila melanogaster. Within the dendrite, receptor subunits localize to different regions and in a spatial order that exactly matches the EM-reconstructed synapse numbers and distributions of the different input neurons described in previous studies. Further, we discovered a strictly segregated subcellular distribution of two voltage-gated ion channels in dendrite vs. axonal fibers in T4/T5 neurons. These findings lay the foundation for future functional investigations of receptors and ion channels in T4/T5 neurons and will be used by biophysically realistic model simulations of the motion-detecting circuit. In summary, we employed new methods to investigate neurotransmitters, their corresponding receptors, and voltage-gated ion channels in the motion vision pathway of the fruit fly. This work advanced our understanding of the biophysical mechanisms of motion-vision. Future studies can build on it to investigate the full molecular repertoire of T4/T5 neurons. Potentially, the strategies presented in this thesis can be expanded to different circuits or even different species in the future

    Easier Parallel Programming with Provably-Efficient Runtime Schedulers

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    Over the past decade processor manufacturers have pivoted from increasing uniprocessor performance to multicore architectures. However, utilizing this computational power has proved challenging for software developers. Many concurrency platforms and languages have emerged to address parallel programming challenges, yet writing correct and performant parallel code retains a reputation of being one of the hardest tasks a programmer can undertake. This dissertation will study how runtime scheduling systems can be used to make parallel programming easier. We address the difficulty in writing parallel data structures, automatically finding shared memory bugs, and reproducing non-deterministic synchronization bugs. Each of the systems presented depends on a novel runtime system which provides strong theoretical performance guarantees and performs well in practice

    Rigorous concurrency analysis of multithreaded programs

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    technical reportThis paper explores the practicality of conducting program analysis for multithreaded software using constraint solv- ing. By precisely defining the underlying memory consis- tency rules in addition to the intra-thread program seman- tics, our approach orders a unique advantage for program ver- ification | it provides an accurate and exhaustive coverage of all thread interleavings for any given memory model. We demonstrate how this can be achieved by formalizing sequen- tial consistency for a source language that supports control branches and a monitor-style mutual exclusion mechanism. We then discuss how to formulate programmer expectations as constraints and propose three concrete applications of this approach: execution validation, race detection, and atom- icity analysis. Finally, we describe the implementation of a formal analysis tool using constraint logic programming, with promising initial results for reasoning about small but non-trivial concurrent programs

    Provably good race detection that runs in parallel

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    Thesis (S.M.)--Massachusetts Institute of Technology, Dept. of Electrical Engineering and Computer Science, 2005.Includes bibliographical references (p. 93-98).A multithreaded parallel program that is intended to be deterministic may exhibit nondeterminism clue to bugs called determinacy races. A key capability of race detectors is to determine whether one thread executes logically in parallel with another thread or whether the threads must operate in series. This thesis presents two algorithms, one serial and one parallel, to maintain the series-parallel (SP) relationships "on the fly" for fork-join multithreaded programs. For a fork-join program with T1 work and a critical-path length of T[infinity], the serial SP-Maintenance algorithm runs in O(T1) time. The parallel algorithm executes in the nearly optimal O(T1/P + PT[infinity]) time, when run on P processors and using an efficient scheduler. These SP-maintenance algorithms can be incorporated into race detectors to get a provably good race detector that runs in parallel. This thesis describes an efficient parallel race detector I call Nondeterminator-3. For a fork-join program T1 work, critical-path length T[infinity], and v shared memory locations, the Nondeterminator-3 runs in O(T1/P + PT[infinity] lg P + min [(T1 lg P)/P, vT[infinity] Ig P]) expected time, when run on P processors and using an efficient scheduler.by Jeremy T. Fineman.S.M

    Homebox genes in mouse fetal thymocyte development

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