The overall aim of SenseLab is to integrate multidisciplinary neuroscience data by means of innovative databases and tools, using the olfactory system as a model which can generalize across the nervous system. For this purpose we have created 8 interoperable databases that serve growing user communities for experimental data and computational models at multiple levels, from genes and proteins through neurons to circuits. SenseLab has three foundations: neuroinformatics directed by Perry Miller, experimental data by Gordon Shepherd, and computational modeling by Michael Hines. One focus will be on ModelDB, which is growing strongly with over 800 computational models. We will build new functionality to enable the models to be explored with new tools including ModelSearch and ModelView. We will support an emerging field of brain microcircuits through MicrocircuitDB, which currently contains over 200 models. A new BrainPathPhysiolDB will contain over 100 models of neuron pathophysiology with clinical relevance. A new ORModelDB will add molecular models to the Olfactory Receptor Database (ORDB) to enhance the utility of the 14,000+ chemosensory genes and proteins that it currently contains. To enhance interoperation we will continue to work closely with the Neuroscience Information Framework (NIF) and the International Neuroinformatics Coordination Facility (INCF) to develop a general ontology for neurons and microcircuits. Support by Dr. Miller and his colleagues in the Yale Center for Medical Informatics will be critical, and enable SenseLab to continue developing its state-of-the-art infrastructure and tools for database construction and interoperation. We will explore innovative ways in which individual SenseLab databases can be designed, adapted, and/or enhanced to facilitate robust interoperation with other neuroscience databases, tools, and resources such as the NIF. In our experimental and computational studies we will develop a new generation of large-scale microcircuit models which realistically represent the detailed 3 dimensional morphology of multiple neuron types with overlapping dendritic fields and distributed synaptic interactions. The NEURON simulator, developed by Dr. Hines, is unique in its capability for computing this model on massively parallel cluster computers. We will test the model with experimental data from an ongoing collaboration with the lab of Dr. Justus Verhagen, and will share the model with other labs working on the olfactory bulb and other systems. In summary, this multidisciplinary and multilevel approach using integration of experimental data into realistic computational simulations should serve as a model for analysis of olfactory processing and for current attempts at data integration throughout the brain.

Public Health Relevance

There is a critical need to understand how signals are processed in neurons and neuronal microcircuits as a basis for brain function. We will enhance this effort through a system of interrelated databases of experimental data and computational models. The new projects open new directions in integrating data to give deeper insights into brain functions and brain disorders.

Agency
National Institute of Health (NIH)
Type
Research Project (R01)
Project #
2R01DC009977-06
Application #
8697553
Study Section
(NOIT)
Program Officer
Sullivan, Susan L
Project Start
Project End
Budget Start
Budget End
Support Year
6
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Yale University
Department
Neurosciences
Type
Schools of Medicine
DUNS #
City
New Haven
State
CT
Country
United States
Zip Code
06510
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
Popovic, Marko A; Gao, Xin; Carnevale, Nicholas T et al. (2014) Cortical dendritic spine heads are not electrically isolated by the spine neck from membrane potential signals in parent dendrites. Cereb Cortex 24:385-95
Chiu, Chiayu Q; Lur, Gyorgy; Morse, Thomas M et al. (2013) Compartmentalization of GABAergic inhibition by dendritic spines. Science 340:759-62
Marenco, Luis N; Bahl, Gautam; Hyland, Lorra et al. (2013) Databases in SenseLab for the genomics, proteomics, and function of olfactory receptors. Methods Mol Biol 1003:3-22
Yu, Yuguo; McTavish, Thomas S; Hines, Michael L et al. (2013) Sparse distributed representation of odors in a large-scale olfactory bulb circuit. PLoS Comput Biol 9:e1003014
McTavish, Thomas S; Migliore, Michele; Shepherd, Gordon M et al. (2012) Mitral cell spike synchrony modulated by dendrodendritic synapse location. Front Comput Neurosci 6:3
Phillips, Matthew E; Sachdev, Robert N S; Willhite, David C et al. (2012) Respiration drives network activity and modulates synaptic and circuit processing of lateral inhibition in the olfactory bulb. J Neurosci 32:85-98
Gulledge, Allan T; Carnevale, Nicholas T; Stuart, Greg J (2012) Electrical advantages of dendritic spines. PLoS One 7:e36007
Kim, David H; Phillips, Matthew E; Chang, Andrew Y et al. (2011) Lateral Connectivity in the Olfactory Bulb is Sparse and Segregated. Front Neural Circuits 5:5