The Neurome Project

Toward a Pan-Mammalian Neurome

In humans, in other mammals, and in complex multicellular organisms in general, evolved cellular diversity is nowhere more evident than in the nervous system [1], whose nerve cells, or neurons, are necessary for the perception of sensation and feeling, the encoding and retrieval of memories, and the control of behavior and emotion—activities that are essential for the survival of the individual, and the species.

Charged with such varied and critical tasks, neurons may be thought of as the stars of the cellular universe, not only for their intrinsic diversity of form and function, but also because collectively, in the brain and nervous system, neurons are the primary cellular units of the single most complex biological system known to exist.

The Neurome Project aims to determine the organization of neuronal connections between nervous system parts—a connectome [2] for each part—with the eventual goal of obtaining a network map for the entire nervous system—a neurome [3]—composed of all connectomes, and including connections between neurons and non-neuronal cells [4]. Pan-mammalian applicability is central to our approach, with analysis of regional connections limited to brain regions with indicated representation across Mammalia.

The nervous system has 11 major parts (figure above: including the intracranial central nervous system, spinal cord, and peripheral ganglia—the latter counted together), giving a total of 242 possible connectomes, including within and between each part (left / right side independent), and the most extensively researched mammal, next to humans, is the rat (for which we currently have the most complete neuronal connection dataset). Our connectome efforts combine rigorous data-driven, expert-led collation of connection reports from the primary literature (e.g. [5]) with current network analysis approaches.

To aid and accelerate the process of neuronal connection data entry, collation, and analysis, the Axiome informatics tools were developed. These modular tools operate with Microsoft Excel to provide a structured and interactive platform for the systematic entry and analysis of neuronal connection, and other brain data [6,7]. Central to Axiome is integration with a reference brain atlas. The current iteration of Axiome is designed for use with a rat brain reference atlas [8].

Our initial efforts have generated new models of brain circuit organization for two of the four main parts of the mammalian forebrain (cerebral cortex and cerebral nuclei). The 'proximal' goal of this project is to complete construction and network analysis of gray matter region-level (macroconnection—[9]) connectomes for the mammalian forebrain. Our 'distal' goal is to achieve this for all brain parts, and eventually the entire nervous system, leading to integration with other brain data (such as gene-expression) at multiple levels of spatial resolution. Through these efforts we seek to develop better models, and gain a deeper understanding, of the brain and nervous system.

References

1. Monro, A. secundus (1783). Observations on the Structure and Functions of the Nervous System: Illustrated with Tables (Creech & Johnson, Edinburgh).

2. Sporns, O., Tononi, G., Kotter, R. (2005). The human connectome: A structural description of the human brain. PLOS Computational Biology, 1, e42. DOI: 10.1371/journal.pcbi.0010042

3. Bota, M., Sporns, O., Swanson, L.W. (2015). Architecture of the cerebral cortical association connectome underlying cognition. Proc Natl Acad Sci U S A, 112, E2093-2101. DOI: 10.1073/pnas.1504394112

4. Swanson, L.W. & Lichtman, J.W. (2016). From Cajal to Connectome and Beyond. Annual Review of Neuroscience, 39, 197-216. DOI: 10.1146/annurev-neuro-071714-033954

5. Hahn, J.D. & Swanson, L.W. (2015). Distinct patterns of neural inputs and outputs of the dorsal and ventral zones of the juxtaventromedial region of the lateral hypothalamic area in the male rat. Front. Syst. Neurosci., 9. DOI: 10.3389/fnsys.2015.00066

6. Swanson, L.W., Sporns, O., Hahn, J.D. (2016). Network architecture of the cerebral nuclei (basal ganglia) association and commissural connectome. Proc Natl Acad Sci U S A, 113, E5972-E5981. DOI: 10.1073/pnas.1613184113

7. Swanson, L.W., Hahn, J.D., Sporns, O. (2017). Organizing principles for the cerebral cortex network of commissural and association connections. Proc Natl Acad Sci U S A, 114, E9692-E9701. DOI: 10.1073/pnas.1712928114

8. Swanson, L.W. (2018). Brain Maps 4.0Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps. Swanson, L.W. (2018). J Comp Neurol, 526, 935-943. DOI: 10.1002/cne.24381

9. Swanson, L.W. & Bota, M. (2010). Foundational model of structural connectivity in the nervous system with a schema for wiring diagrams, connectome, and basic plan architecture. Proc Natl Acad Sci U S A, 107, 20610-20617. DOI: 10.1073/pnas.1015128107

Sponsors

Support for The Neurome Project from The Kavli Foundation is gratefully acknowledged, and for support in promoting the Axiome tools, the Stevens Center for Innovation of the University of Southern California (USC).

Header Image: (left line diagram) A theoretical prototypical circuit for the control of behavior involving visual sensory input, central integration, and motor output (adapted from L'Homme. René Descartes. 1664); (right line diagram) A later empirical theoretical schema for control of behavior based on neuronal architecture and connections (adapted from Les nouvelles idées sur la structure du système nerveux chez l'homme et chez les vertébrés. Santiago Ramón y Cajal. 1894). The line diagrams are overlaid on an image acquired from the Hubble space telescope in 2016. Light from the stars of several galaxies is visible in a field parallel to galaxy cluster Abell S1063, located some 4 billion light years distant to planet Earth (coincidentally a similar time period from the earliest appearance of life on Earth).