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 individual and species survival. 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 the different parts of the nervous system—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 data-driven approach combines rigorous analysis of connection reports (e.g. [7]) with current informatics and computational network analysis methods (e.g. [8]).

To date, our research has revealed principles of brain circuit organization for the four principal parts of the mammalian forebrain: The cerebral nuclei (or basal ganglia) [9], the cerebral cortex [10], and their combined structure (the endbrain) [11], and more recently the hypothalamus [12] and thalamus [13], and their combined structure (the interbrain) [14]. 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. 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 USA. 112(16): 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 USA. 107(48): 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(6): 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. 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 USA. 113(40): 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 USA. 114(45): 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 USA. 115(29): E6910-E6919. doi: 10.1073/pnas.1807255115

12. Hahn, J.D., Sporns, O., Watts, A.G., Swanson, L.W. (2019). Macroscale intrinsic network architecture of the hypothalamus. Proc Natl Acad Sci USA. 116(16): 8018-8027. doi: 10.1073/pnas.1819448116

13. Swanson, L.W., Sporns, O., Hahn, J.D. (2019). The network organization of rat intrathalamic macroconnections and a comparison with other forebrain divisions. Proc Natl Acad Sci USA. 116(27): 13661-13669. doi: 10.1073/pnas.1905961116

14. Swanson, L.W., Sporns, O., Hahn, J.D. (2019) The network architecture of rat intrinsic interbrain (diencephalon) macroconnections and a comparison with endbrain (telencephalon) architecture. Proc Natl Acad Sci USA. 116(52): 26991-27000. doi: 10.1073/pnas.1915446116

Media Coverage

Neurobiologists help untangle the brain’s life-support network (EurekAlert, March 26, 2019; USC, April 3, 2019).

Sponsors

Support for The Neurome Project from The Kavli Foundation is gratefully acknowledged, and for support in promoting the development of computer-based collation tools (Axiome), 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 about the same period of time since the earliest appearance of life on Earth).