Abstract
Understanding the rat neurochemical connectome is fundamental for exploring neuronal information processing. By using advanced data mining, supervised machine learning, and network analysis, this study integrates over 5 decades of neuroanatomical investigations into a multiscale, multilayer neurochemical connectome of the rat brain. This neurochemical connectivity database (ChemNetDB) is supported by comprehensive systematically-determined receptor distribution maps. The rat connectome has an onion-type structural organization and shares a number of structural features with mesoscale connectomes of mouse and macaque. Furthermore, we demonstrate that extremal values of graph theoretical measures (e.g., degree and betweenness) are associated with evolutionary-conserved deep brain structures such as amygdala, bed nucleus of the stria terminalis, dorsal raphe, and lateral hypothalamus, which regulate primitive, yet fundamental functions, such as circadian rhythms, reward, aggression, anxiety, and fear. The ChemNetDB is a freely available resource for systems analysis of motor, sensory, emotional, and cognitive information processing.
Highlights
The mammalian brain consists of a network of chemically diverse, multiscale, and multilayer neuronal wiring patterns that form the physical infrastructure underlying the processing of motoric, sensory, emotional, and cognitive information
We present an open-access database (ChemNetDB) that organizes over 50 years of neuroanatomical track-tracing and neurochemical measurements from 36,464 rats
4,517 studies were relevant for data mining and data from 1,560 original research articles with 36,464 rats were selected for the connectome identification based on the inclusion
Summary
Standardized data mining and database creationSearch strategy. The online portal of the National Library of Medicine (http://www.ncbi. nlm.nih.gov/pubmed/) including PubMed, PubMed Central, and MEDLINE was used as the platform for literature research. A systematic screening of the original research articles published until February 2015 was performed based on 1,750 keywords (see S2 Text). For hippocampal formation, the search strategy was further extended to include the hippocampome [10]. Among these studies, only peer-reviewed original research articles in English language were chosen for data mining if they provided consistent information on chemoarchitecture, cytoarchitecture, cerebral intra- or interregional connectivities, mRNA expression levels, and/or receptor distribution densities. Thereby, only studies conducted on rats not associated with any disease-model, geno- or phenotype were included, which used anterograde tracing with radioactive amino acids, and autoradiographic fiber tracing methods, as well as anterograde and retrograde tracing with horseradish peroxidase, in situ hybridization, immunohistochemistry or immunocytochemistry as applied technique. Functional connectivity as measured by magnetic resonance imaging or electrical stimulation was excluded as the correspondence between anatomical projections
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