The discovery that new neurons can arise in adult brains--a feat first observed in songbirds--overturned the long-held belief that a vertebrate's complete supply of neurons is created at birth or soon thereafter. In the new work, Fernando Nottebohm of Rockefeller University and his colleagues investigated how latecomer neurons differ from lifelong ones. The researchers injected two types of dye into the brains of 19 songbirds and collected samples from both types of neurons, which are used in two different pathways in the brain. After analyzing genetic information from more than 3,000 cells from each animal, the team determined that one gene (UCHL1) showed remarkably low activity in the newer, or "replaceable neurons": the longstanding ones exhibited 2.5 times the amount of the UCHL1 protein. "Low levels of UCHL1 appear to be a feature of replaceable neurons wherever they occur," says study co-author Anthony Lombardino of Rockefeller University.
Work with mice confirmed the correlation between low levels of UCHL1 and replaceable neurons. Finally, the scientists investigated whether levels of UCHL1 change when the animals sing--an activity that had previously been shown to increase the odds of survival for newly generated neurons. After the male birds sang to a female, the levels of UCHL1 in their replaceable neurons had increased. "These findings suggest that rising levels of UCHL1 may be associated with a reduced risk of neuronal death," Nottebohm explains. The results, published online this week by the Proceedings of the National Academy of Sciences, complement other studies that had linked deficiencies in UCHL1 to degenerative diseases such as Alzheimer's and Parkinson's disease.