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 subconnectomes, and including connections between neurons and non-neuronal cells [4]. Our current analysis is at a macroscale level of granularity—that is at the level of gray matter regions (a macroconnection [5] is a connection between two gray matter regions).

Pan-mammalian applicability is central to our approach, with analysis of regional connections limited to brain regions with indicated representation across Mammalia. We selected the rat as a model mammal because it is the mammal for which the most comprehensive published connection data exists, and because analysis of this data is supported by a rat brain reference atlas that is ideally suited to these efforts [6].

The nervous system has 11 major parts or divisions (figure at top: including the intracranial central nervous system, spinal cord, and peripheral ganglia—the latter counted together), giving a total of 242 possible subconnectomes, including within and between each part (left / right side independent). Our evidence-based approaches combine rigorous analysis of connection reports (e.g. [7]) with current network analysis methods (e.g. [8]).

To date, our research has led to new models of brain circuit organization for two of the four main parts of the mammalian forebrain (cerebral nuclei [9] and cerebral cortex [10]), and their combined structure (the endbrain) [11]). The 'proximal' goal of this project is to complete construction and network analysis of macroconnection subconnectomes for the mammalian forebrain. Our 'distal' goal is to achieve this for all major 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 [4]. Through these efforts we seek to develop better models, and a clearer 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 Comput Biol. 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. Annu Rev Neurosci. 39, 197-216. doi: 10.1146/annurev-neuro-071714-033954

5. 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

6. 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

7. 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

8. Jeub, L.G.S., Sporns, O., Fortunato, S. (2018). Multiresolution consensus clustering in networks. Sci Rep. 8:3259. doi: 10.1038/s41598-018-21352-7

9. 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

10. 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

11. Swanson, L.W., Hahn, J.D., Jeub, L.G.S., Fortunato, S., Sporns, O. (2018). Subsystem organization of axonal connections within and between the right and left cerebral cortex and cerebral nuclei (endbrain). Proc Natl Acad Sci U S A. 115. doi: 10.1073/pnas.1807255115 [Epub ahead of print]

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).