Brain wiring is guided by activity even in very early development

In humans, the process of learning is driven by different groups of cells in the brain firing together. For instance, when the neurons associated with the process of recognizing a dog begin to fire in a coordinated manner in response to the cells that encode the features of a dog - four legs, fur, a tail, etc. - a young child will eventually be able to identify dogs going forward. But brain wiring begins before humans are born, before they have experiences or senses like sight to guide this cellular circuitry. How does that happen?

In a new study published Aug. 15 in Science, Yale researchers identified how brain cells begin to coalesce into this wired network in early development before experience has a chance to shape the brain. It turns out that very early development follows the same rules as later development - cells that fire together wire together. But rather than experience being the driving force, it's spontaneous cellular activity.

For the study, researchers focused on mouse retinal ganglion cells, which project from the retina to a region of the brain called the superior colliculus where they connect to downstream target neurons. The researchers simultaneously measured the activity of a single retinal ganglion cell, the anatomical changes that occurred in that cell during development, and the activity of surrounding cells in awake neonatal mice whose eyes had not yet opened. This technically complex experiment was made possible by advanced microscopy techniques and fluorescent proteins that indicate cell activity and anatomical changes.

The researchers found that when the activity of a single retinal ganglion cell was highly synchronized with waves of spontaneous activity in surrounding cells, the single cell's axon - the part of the cell that connects to other cells - grew new branches. When the activity was poorly synchronized, axon branches were instead eliminated.