Scientists solve birth and migration mysteries of cortex’s powerful inhibitors, ‘chandelier’ cells

The cerebral cortex of the human brain has been called “the crowning achievement of evolution.” Ironically, it is so complex that even our greatest minds and most sophisticated science are only now beginning to understand how it organizes itself in early development, and how its many cell types function together as circuits.

A major step toward this great goal in neuroscience has been taken by a team led by Professor Z. Josh Huang, Ph.D., at Cold Spring Harbor Laboratory (CSHL). Today they publish research for the first time revealing the birth timing and embryonic origin of a critical class of inhibitory brain cells called chandelier cells, and tracing the specific paths they take during early development into the cerebral cortex of the mouse brain. 

These temporal and spatial sequences are regarded by Huang as genetically programmed aspects of brain development, accounting for aspects of the brain that are likely identical in every member of a given species, including humans. Exceptions to these stereotypical patterns include irregularities caused by gene mutations or protein malfunctions, both of which are now being identified in people with developmental disorders and neuropsychiatric illnesses.

Chandelier cells were first noticed only 40 years ago, and in the intervening years frustratingly little has been learned about them, beyond the fact that they “hang” individually among great crowds of excitatory cells in the cortex called pyramidal neurons, and that their relatively short branches make contact with these excitatory cells.  Indeed, a single chandelier cell connects, or “synapses,” with as many as 500 pyramidal neurons. Noting this, the great biologist Francis Crick decades ago speculated that chandelier cells exerted some kind of “veto” power over the messages being exchanged by the much more numerous excitatory cells in their vicinity.