A Proposal for a Coordinated Effort for the Determination of Brainwide Neuroanatomical Connectivity in Model Organisms at a Mesoscopic Scale

TLDR

Neuroanatomical circuitry remains surprisingly sparse even in the era of complete genomes, yet it is essential for both basic and clinical brain research. We propose a coordinated, systematic effort to map neural circuits at a mesoscopic resolution using tracer or viral vector injections to achieve comprehensive brain‑wide coverage. The proposal outlines the scientific rationale, reviews existing techniques, sets desiderata for coverage, validated and extensible methods, open‑access data, compatibility with current resources, and presents a tractable plan for mice, macaques, and humans. We estimate that the mouse connectivity project could be finished within five years on a modest budget.

Abstract

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.