The SenseLab suite of 8 interoperable databases is aimed at supporting our research on a model system for brain organization, the olfactory bulb, and at sharing these and related resources with the neuroscience and neuroinformatics communities. During the past 5 years a Program Project grant has enabled us to begin to move from the synaptic and cell levels to the microcircuit level, and in this R01 grant we will build directly on this work. First, we will continue development of our most heavily used databases - NeuronDB and ModelDB - for the analysis of dendritic signal integration, and ORDB, supporting work on olfactory receptors, the largest family in the genome. We will continue to participate in the Neuroscience Database Gateway, the Neuroscience Information Framework, and the International Neuroinformatics Coordinating Facility. We will continue to demonstrate how databases support neuroscience research with two new research projects to develop computational models that give insight into experimental data. One project is to deepen insight into our recent experimental evidence from transsynaptic tracing for widely distributed cell columns, which we hypothesize are involved in processing odor maps. We will analyze this data and use it to refine first a reduced microcircuit in which the glomerular cell columns respond to the excitatory input from the odor maps and process it through distance-independent lateral inhibition between glomerular columns. With continual testing by the experimental data, we will scale up the model to 100 columns, then to 2,000, to characterize the global processing of odor maps to an extent not possible with experimental methods. This work will be carried out as a pilot project in parallel with the Blue Brain Project in Switzerland on realistically-based large- scale cortical networks. A new database, MicrocircuitDB, will be developed to support this and related studies of microcircuit organization. A second new project will extend our computational analysis of energy demands in the olfactory glomerulus to the lateral inhibitory interactions, to provide a more thorough understanding of the energy demands of the microcircuits that process odor maps. A new database project is to apply NeuronDB and ModelDB to analyzing the impact of the early pathogenesis of neurodegenerative disorders on dendritic signal integration. For this purpose we are developing a new database, Brain Pharmacology (BrainPharm). All of this work will benefit from continued support and development by the Yale Center for Medical Informatics, and by the NEURON simulation environment team.

Public Health Relevance

There is a critical need to understand how signals are processed in nerve cells and nerve circuits as a basis for brain function. We attempt to enhance this effort through a system of interrelated databases of experimental data and computer models. The new projects should give a deeper understanding of both normal brain function and neurological disorders such as Alzheimer's disease

Agency
National Institute of Health (NIH)
Institute
National Institute on Deafness and Other Communication Disorders (NIDCD)
Type
Research Project (R01)
Project #
5R01DC009977-04
Application #
8296322
Study Section
Neurotechnology Study Section (NT)
Program Officer
Sullivan, Susan L
Project Start
2009-08-01
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$649,654
Indirect Cost
$257,114
Name
Yale University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
043207562
City
New Haven
State
CT
Country
United States
Zip Code
06520
Rowe, Timothy B; Shepherd, Gordon M (2016) Role of ortho-retronasal olfaction in mammalian cortical evolution. J Comp Neurol 524:471-95
Marasco, Addolorata; De Paris, Alessandro; Migliore, Michele (2016) Predicting the response of olfactory sensory neurons to odor mixtures from single odor response. Sci Rep 6:24091
McDougal, Robert A; Morse, Thomas M; Carnevale, Ted et al. (2016) Twenty years of ModelDB and beyond: building essential modeling tools for the future of neuroscience. J Comput Neurosci :
Zhou, Shanglin; Migliore, Michele; Yu, Yuguo (2016) Odor Experience Facilitates Sparse Representations of New Odors in a Large-Scale Olfactory Bulb Model. Front Neuroanat 10:10
Sivagnanam, Subhashini; Majumdar, Amit; Yoshimoto, Kenneth et al. (2015) Early experiences in developing and managing the neuroscience gateway. Concurr Comput 27:473-488
Popovic, Marko A; Carnevale, Nicholas; Rozsa, Balazs et al. (2015) Electrical behaviour of dendritic spines as revealed by voltage imaging. Nat Commun 6:8436
Migliore, Michele; Cavarretta, Francesco; Marasco, Addolorata et al. (2015) Synaptic clusters function as odor operators in the olfactory bulb. Proc Natl Acad Sci U S A 112:8499-504
McDougal, Robert A; Morse, Thomas M; Hines, Michael L et al. (2015) ModelView for ModelDB: Online Presentation of Model Structure. Neuroinformatics 13:459-70
McDougal, Robert A; Shepherd, Gordon M (2015) 3D-printer visualization of neuron models. Front Neuroinform 9:18
Yu, Yuguo; Migliore, Michele; Hines, Michael L et al. (2014) Sparse coding and lateral inhibition arising from balanced and unbalanced dendrodendritic excitation and inhibition. J Neurosci 34:13701-13

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