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J Douglas Armstrong

Publications and source records attributed to J Douglas Armstrong.

8 recordsLinked to original sources
PubMed2007

Sequential use of mushroom body neuron subsets during drosophila odor memory processing.

Drosophila mushroom bodies (MB) are bilaterally symmetric multilobed brain structures required for olfactory memory. Previous studies suggested that neurotransmission from MB neurons is only required for memory retrieval. Our unexpected observation that Dorsal Paired Medial (DPM) neurons, which project only to MB neurons, are required during memory storage but not during acquisition or retrieval, led us to revisit the role of MB neurons in memory processing. We show that neurotransmission from the alpha'beta' subset of MB neurons is required to acquire and stabilize aversive and appetitive odor memory, but is dispensable during memory retrieval. In contrast, neurotransmission from MB alphabeta neurons is only required for memory retrieval. These data suggest a dynamic requirement for the different subsets of MB neurons in memory and are consistent with the notion that recurrent activity in an MB alpha'beta' neuron-DPM neuron loop is required to stabilize memories formed in the MB alphabeta neurons.

Animals↗
PubMed2006

The proteomes of neurotransmitter receptor complexes form modular networks with distributed functionality underlying plasticity and behaviour.

Neuronal synapses play fundamental roles in information processing, behaviour and disease. Neurotransmitter receptor complexes, such as the mammalian N-methyl-D-aspartate receptor complex (NRC/MASC) comprising 186 proteins, are major components of the synapse proteome. Here we investigate the organisation and function of NRC/MASC using a systems biology approach. Systematic annotation showed that the complex contained proteins implicated in a wide range of cognitive processes, synaptic plasticity and psychiatric diseases. Protein domains were evolutionarily conserved from yeast, but enriched with signalling domains associated with the emergence of multicellularity. Mapping of protein-protein interactions to create a network representation of the complex revealed that simple principles underlie the functional organisation of both proteins and their clusters, with modularity reflecting functional specialisation. The known functional roles of NRC/MASC proteins suggest the complex co-ordinates signalling to diverse effector pathways underlying neuronal plasticity. Importantly, using quantitative data from synaptic plasticity experiments, our model correctly predicts robustness to mutations and drug interference. These studies of synapse proteome organisation suggest that molecular networks with simple design principles underpin synaptic signalling properties with important roles in physiology, behaviour and disease.

Animals↗
PubMed2006

Reconstructing protein complexes: from proteomics to systems biology.

Modern high throughput technologies in biological science often create lists of interesting molecules. The challenge is to reconstruct a descriptive model from these lists that reflects the underlying biological processes as accurately as possible. Once we have such a model or network, what can we learn from it? Specifically, given that we are interested in some biological process associated with the model, what new properties can we predict and subsequently test? Here, we describe, at an introductory level, a range of bioinformatics techniques that can be systematically applied to proteomic datasets. When combined, these methods give us a global overview of the network and the properties of the proteins and their interactions. These properties can then be used to predict functional pathways within the network and to examine substructure. To illustrate the application of these methods, we draw upon our own work concerning a complex of 186 proteins found in neuronal synapses in mammals. The techniques discussed are generally applicable and could be used to examine lists of proteins involved with the biological response to electric or magnetic fields.

Animals↗
PubMed2005

Synapse proteomics of multiprotein complexes: en route from genes to nervous system diseases.

Proteomic experiments have produced a draft profile of the overall molecular composition of the mammalian neuronal synapse. It appears that synapses have over 1000 protein components and the mapping of their interactions, organization and functions will lead to a global view of the role of synapses in physiology and disease. A major functional subcomponent of the synaptic machinery is a multiprotein complex of glutamate receptors and adhesion proteins with associated adaptor and signalling enzymes totally 185 proteins known as the N-methyl-d-aspartate receptor complex/MAGUK associated signalling complex (NRC/MASC). Here, we review the proteomic studies and functions of NRC/MASC and specifically report on the role of its component genes in human diseases. Using a systematic literature search protocol, we identified reports of mutations or polymorphisms in 47 genes associated with 183 disorders, of which 54 were nervous system disorders. A similar number of genes are important in mouse synaptic plasticity and behaviour, where the NRC/MASC acts as a signalling complex with multiple functions provided by its individual protein components and their interactions. The individual gene mutations suggest not only an important role for the NRC/MASC in human diseases but that these diseases may be functionally connected by their common link to the NRC/MASC. The NRC/MASC is a rich source of genetic variation and provides a platform for understanding relationships of disease phenotype amenable to systematic studies such as the Genes to Cognition research consortium (www.genes2cognition.org) that links human and mouse genetics with proteomic studies.

Humans↗
PubMed2005

Genetics of graviperception in animals.

Gravity is a constant stimulus for life on Earth and most organisms have evolved structures to sense gravitational force and incorporate its influence into their behavioral repertoire. Here we focus attention on animals and their diverse structures for perceiving and responding to the gravitational vector-one of the few static reference stimuli for any mobile organism. We discuss vertebrate, arthropod, and nematode models from the perspective of the role that genetics is playing in our understanding of graviperception in each system. We describe the key sensory structures in each class of organism and present what is known about the genetic control of development of these structures and the molecular signaling pathways operating in the mature organs. We also discuss the role of large genetic screens in identifying specific genes with roles in mechanosensation and graviperception.

Animals↗
PubMed2005

Drosophila melanogaster--the model organism of choice for the complex biology of multi-cellular organisms.

Drosophila melanogaster has been intensely studied for almost 100 years. The sophisticated array of genetic and molecular tools that have evolved for analysis of gene function in this organism are unique. Further, Drosophila is a complex multi-cellular organism in which many aspects of development and behavior parallel those in human beings. These combined advantages have permitted research in Drosophila to make seminal contributions to the understanding of fundamental biological processes and ensure that Drosophila will continue to provide unique insights in the genomic era. An overview of the genetic methodologies available in Drosophila is given here, together with examples of outstanding recent contributions of Drosophila to our understanding of cell and organismal biology. The growing contribution of Drosophila to our knowledge of gravity-related responses is addressed.

Animals↗
PubMed2004

radish encodes a phospholipase-A2 and defines a neural circuit involved in anesthesia-resistant memory.

BACKGROUND: In both vertebrate and invertebrate animals, anesthetic agents cause retrograde amnesia for recently experienced events. In contrast, older memories are resistant to the same treatments. In Drosophila, anesthesia-resistant memory (ARM) and long-term memory (LTM) are genetically distinct forms of long-lasting memory that exist in parallel for at least a day after training. ARM is disrupted in radish mutants but is normal in transgenic flies overexpressing a CREB repressor transgene. In contrast, LTM is normal in radish mutants but is disrupted in CREB repressor transgenic flies. To date, nothing is known about the molecular, genetic, or cell biological pathways underlying ARM. RESULTS: Here, we report the molecular identification of radish as a phospholipase-A2, providing the first clue about signaling pathways underlying ARM in any animal. An enhancer-trap allele of radish (C133) reveals expression in a novel anatomical pathway. Transgenic expression of PLA2 under control of C133 restores normal levels of ARM to radish mutants, whereas transient disruption of neural activity in C133 neurons inhibits memory retention. Notably, expression of C133 is not in mushroom bodies, the primary anatomical focus of olfactory memory research in Drosophila. CONCLUSIONS: Identification of radish as a phospholipase-A2 and the neural expression pattern of an enhancer-trap allele significantly broaden our understanding of the biochemistry and anatomy underlying olfactory memory in Drosophila.

Alleles↗