Nian Liu

Simultaneous activation of mouse main and accessory olfactory bulbs by odors or pheromones

It is generally believed that the main olfactory system processes common odors and the accessory olfactory system is specifically for pheromones. The potential for these two systems to respond simultaneously to the same stimuli has not been fully explored due to methodological limitations. Here we examine this phenomenon using high‐resolution functional magnetic resonance imaging (fMRI) to reveal simultaneously the responses in the main (MOB) and accessory olfactory bulbs (AOB) to odors and pheromones. Common odorants elicited strong signals in the MOB and weak signals in the AOB. 2‐Heptanone, a known mouse pheromone, elicited strong signals in both the MOB and AOB. Urine odor, a complicated mixture of pheromones and odorants, elicited significant signals in limited regions of the MOB and large regions of the AOB. The fMRI results demonstrate that both the main and the accessory olfactory systems may respond to volatile compounds but with different selectivity, suggesting a greater integration of the two olfactory pathways than traditionally believed. J. Comp. Neurol. 489:491–500, 2005.

Odor maps of aldehydes and esters revealed by functional MRI in the glomerular layer of the mouse olfactory bulb

Odorant identity is believed to be encoded in the olfactory bulb (OB) by glomerular activity patterns. It has not yet been possible to visualize and compare entire patterns for different odorants in the same animal because of technical limitations. For this purpose we used high-resolution functional MRI at 7 T, combined with glomerular-layer flat maps, to reveal responses to aliphatic homologues in the mouse OB. These odorants elicited reproducible patterns in the OB, with the medial and lateral regions containing the most intense signals. Unexpectedly, in view of the symmetrical projections of olfactory receptor neurons to medial and lateral glomeruli, the activity patterns in these regions were asymmetrical. The highly activated medial and lateral areas were shared by homologous members, generating a conserved “family signature” for a homologous series. The moderately active areas, including the dorsal region that has been extensively studied by optical imaging, were more sensitive to the length of the carbon chain, producing more subtle features of individual members and different changing trends among homologues. The global mapping with functional MRI not only extended previous studies but also revealed additional rules for representation of homologues in the OB. Insights into possible relations between the functional patterns, molecular projections, and odor perception may now be obtained based on the global from the olfactory epithelium to the OB glomerular activity patterns.

AlzPharm: integration of neurodegeneration data using RDF

BackgroundNeuroscientists often need to access a wide range of data sets distributed over the Internet. These data sets, however, are typically neither integrated nor interoperable, resulting in a barrier to answering complex neuroscience research questions. Domain ontologies can enable the querying heterogeneous data sets, but they are not sufficient for neuroscience since the data of interest commonly span multiple research domains. To this end, e-Neuroscience seeks to provide an integrated platform for neuroscientists to discover new knowledge through seamless integration of the very diverse types of neuroscience data. Here we present a Semantic Web approach to building this e-Neuroscience framework by using the Resource Description Framework (RDF) and its vocabulary description language, RDF Schema (RDFS), as a standard data model to facilitate both representation and integration of the data.ResultsWe have constructed a pilot ontology for BrainPharm (a subset of SenseLab) using RDFS and then converted a subset of the BrainPharm data into RDF according to the ontological structure. We have also integrated the converted BrainPharm data with existing RDF hypothesis and publication data from a pilot version of SWAN (Semantic Web Applications in Neuromedicine). Our implementation uses the RDF Data Model in Oracle Database 10g release 2 for data integration, query, and inference, while our Web interface allows users to query the data and retrieve the results in a convenient fashion.ConclusionAccessing and integrating biomedical data which cuts across multiple disciplines will be increasingly indispensable and beneficial to neuroscience researchers. The Semantic Web approach we undertook has demonstrated a promising way to semantically integrate data sets created independently. It also shows how advanced queries and inferences can be performed over the integrated data, which are hard to achieve using traditional data integration approaches. Our pilot results suggest that our Semantic Web approach is suitable for realizing e-Neuroscience and generic enough to be applied in other biomedical fields.

Informatics approaches to functional MRI odor mapping of the rodent olfactory bulb: OdorMapBuilder and OdorMapDB.

The present study applies informatics tools to aid and extend fMRI analysis of the coding mechanism of neural signals in the rodent olfactory system. Odor stimulation evokes unique spatial patterns of activity in the glomerular layer of the mammalian olfactory bulb (OB). An open-source software program, OdorMapBuilder, has been developed to process the high resolution anatomical and functional MRI images of the OB and to generate single two-dimensional flat maps, called odor maps, that describe the spatial activity patterns in the entire glomerular layer. Odor maps help identify the spatial activity patterns from the tremendous amount of fMRI data and they serve as ideal representation of space coding for the olfactory signals in the OB in response to a given odor stimulation. Based on the fMRI technology, OdorMapBuilder provides comparable odor maps on the intra-subject basis, a significant step towards the detailed analyses of the effects of odor types and/or concentrations. In addition, a new database, OdorMapDB, is developed to provide a repository for the generated odor maps. Web interfaces to the database are provided for the data entry, modification and retrieval. OdorMapDB is based on the EAV/CR (entity-attribute-value with classes and relationships) architecture and it is integrated with two other SenseLab olfactory databases: the olfactory receptor and odor databases. Both OdorMapBuilder and OdorMapDB should serve as useful tools and resources for the field and help facilitate experimental research in understanding the olfactory system and the mechanism for smell perception.

ResourceLog: An Embeddable Tool for Dynamically Monitoring the Usage of Web-Based Bioscience Resources

The present study described an open source application, ResourceLog, that allows website administrators to record and analyze the usage of online resources. The application includes four components: logging, data mining, administrative interface, and back-end database. The logging component is embedded in the host website. It extracts and streamlines information about the Web visitors, the scripts, and dynamic parameters from each page request. The data mining component runs as a set of scheduled tasks that identify visitors of interest, such as those who have heavily used the resources. The identified visitors will be automatically subjected to a voluntary user survey. The usage of the website content can be monitored through the administrative interface and subjected to statistical analyses. As a pilot project, ResourceLog has been implemented in SenseLab, a Web-based neuroscience database system. ResourceLog provides a robust and useful tool to aid system evaluation of a resource-driven Web application, with a focus on determining the effectiveness of data sharing in the field and with the general public.

OdorMapComparer: An Application for Quantitative Analyses and Comparisons of fMRI Brain Odor Maps

Brain odor maps are reconstructed flat images that describe the spatial activity patterns in the glomerular layer of the olfactory bulbs in animals exposed to different odor stimuli. We have developed a software application, OdorMapComparer, to carry out quantitative analyses and comparisons of the fMRI odor maps. This application is an open-source window program that first loads two odor map images being compared. It allows image transformations including scaling, flipping, rotating, and warping so that the two images can be appropriately aligned to each other. It performs simple subtraction, addition, and average of signals in the two images. It also provides comparative statistics including the normalized correlation (NC) and spatial correlation coefficient. Experimental studies showed that the rodent fMRI odor maps for aliphatic aldehydes displayed spatial activity patterns that are similar in gross outlines but somewhat different in specific subregions. Analyses with OdorMapComparer indicate that the similarity between odor maps decreases with increasing difference in the length of carbon chains. For example, the map of butanal is more closely related to that of pentanal (with a NC = 0.617) than to that of octanal (NC = 0.082), which is consistent with animal behavioral studies. The study also indicates that fMRI odor maps are statistically odor-specific and repeatable across both the intra- and intersubject trials. OdorMapComparer thus provides a tool for quantitative, statistical analyses and comparisons of fMRI odor maps in a fashion that is integrated with the overall odor mapping techniques.

Integrated olfactory receptor and microarray gene expression databases

BackgroundGene expression patterns of olfactory receptors (ORs) are an important component of the signal encoding mechanism in the olfactory system since they determine the interactions between odorant ligands and sensory neurons. We have developed the Olfactory Receptor Microarray Database (ORMD) to house OR gene expression data. ORMD is integrated with the Olfactory Receptor Database (ORDB), which is a key repository of OR gene information. Both databases aim to aid experimental research related to olfaction.DescriptionORMD is a Web-accessible database that provides a secure data repository for OR microarray experiments. It contains both publicly available and private data; accessing the latter requires authenticated login. The ORMD is designed to allow users to not only deposit gene expression data but also manage their projects/experiments. For example, contributors can choose whether to make their datasets public. For each experiment, users can download the raw data files and view and export the gene expression data. For each OR gene being probed in a microarray experiment, a hyperlink to that gene in ORDB provides access to genomic and proteomic information related to the corresponding olfactory receptor. Individual ORs archived in ORDB are also linked to ORMD, allowing users access to the related microarray gene expression data.ConclusionORMD serves as a data repository and project management system. It facilitates the study of microarray experiments of gene expression in the olfactory system. In conjunction with ORDB, ORMD integrates gene expression data with the genomic and functional data of ORs, and is thus a useful resource for both olfactory researchers and the public.

Databases for the Functional Analyses of Olfactory Receptors

The olfactory receptors constitute over 1000 genes, making it the largest family in the genome. The completion of the human and mouse genomes presents a tremendous challenge to understanding the odor ligand affinities of these receptors and their relation to odor processing in the olfactory system. We describe briefly the practical use of a set of databases in the SenseLab project (http://senselab.med.yale.edu/) that is devoted to this problem. Olfactory Receptor Database (ORDB) archives almost 2000 sequences, and provides tools for their analysis by type. OdorDB stores data about the structures of odor molecules and their affinities for different olfactory receptors, as established by studies in expression systems. Odor simulation gives rise to odor maps in the olfactory bulb which is believed to be a basis for odor discrimination. OdorMapDB provides a site for integration of data from odor mapping studies by different methods. These databases thus enable students and researchers to integrate molecular analysis of olfactory receptors with the functional organization of the olfactory system to understand the neural basis of the sense of smell.

Coding of Peripheral Olfactory Information in the Olfactory Bulb of Small Animals

The activity pattern in the olfactory bulb is generally believed to code for the peripheral olfactory information. To reveal how chemical structure and experimental parameters are represented by the patterns, high resolution functional MRI was used to map the responses of the bulb to various stimuli under different conditions. The results revealed that different odorants elicited specific and reproducible patterns. Pattern similarity (difference) parallels structure similarity (difference). Experimental parameters, such as odorant concentration and exposure duration, strongly affect pattern intensity, but have little effects on the pattern topography. The results provided evidence for the hypothesis that the pattern intensity codes for the stimulation strength and pattern topography codes for chemical structure.