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

Abstract

In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is critical, however, for both 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, brainwide 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 brainwide 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.

Figure 1. Current knowledge of rat brain connectivity available in the Brain Architecture Management System ,.

This matrix shows information that has thus far been curated about projections between 486 discrete brain regions in the rat brain. Non-white entries indicate connections for which data are available. Black entries indicate the absence of a connection, and colored entries indicate reported connections of varying strength. The overall sparsity of this matrix (10.45% filled) is reflective of our lack of a unified understanding of brain connectivity in model organisms.