A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

TL;DR

This paper advocates for a coordinated, systematic effort to map brain-wide neuroanatomical connectivity at a mesoscopic scale in model organisms, emphasizing standardization, automation, and open data sharing.

Contribution

It proposes a comprehensive plan for large-scale neural circuit mapping using experimental techniques suitable for automation and standardization, aiming to fill critical gaps in neuroanatomical knowledge.

Findings

A feasible five-year plan for mouse brain connectivity mapping.

Identification of key requirements for a standardized neuroanatomical mapping effort.

Discussion of extending techniques to macaque and human brains.

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.