What does the very first complex vertebrate brain look like? To find out, scientists turn to an unlikely time traveler: the lamprey, a jawless, eel-like fish whose body plan has barely changed in roughly 360 million years.

In a study published in Science on June 18, a team of researchers led by SU Bing from the Kunming Institute of Zoology of the Chinese Academy of Sciences, along with collaborators from BGI-Research and Liaoning Normal University, built the first three-dimensional, single-cell atlas of an entire lamprey brain, which is essentially a high-resolution map showing where every cell sits and which genes it switches on.

The researchers found that although lampreys diverged from jawed vertebrates about 450 million years ago, their brains share strikingly similar gene-expression patterns with the mouse across many regions. This finding suggests that the common ancestor of all vertebrates likely already had a well-organized, molecularly complex brain.

However, the researchers showed that each lineage also invented its own tricks: the lamprey has unique midbrain neurons and oversized "Müller cells," while mammals went on to build the elaborate, layered cortex.

Moreover, the atlas hinted at how neuronal types became more specialized over the course of evolution. In the lamprey, many cells "moonlight," carrying both excitatory and inhibitory signals at once—a versatile type named anamniote-enriched neurons, or AEN.

Comparing living species across the vertebrate tree, the researchers found these "moonlighting" cells common in jawless and other anamniote lineages but rare in jawed animals which lean instead on "specialist" neurons with dedicated jobs. The contrast tracks an ancient whole-genome duplication.

In addition, the researchers revealed that even the cerebellum, the brain's coordination hub, showed early roots: lamprey cells resembling cerebellar neurons point to a diffuse, primitive "proto-cerebellum."

The findings of this study reconstruct the brain's ancient blueprint, and provide a new perspective on how complexity arose including, perhaps, the deep history of our own minds.

Three-dimensional reconstruction of the lamprey whole brain. (Image by Kunming Institute of Zoology)

The study featured on the cover of Science. (Image by Kunming Institute of Zoology)