Grantee: The Salk Institute for Biological Studies, San Diego, CA, USA
Project Lead: Fred H. Gage, Ph.D.Co-PIs: Scott Small, Andrea Chiba, Ayumyu Tashiro and Janet Wiles
Grant Title: Neurogenesis in rodents: genetic and molecular approaches to study the physiology of neurogenesis and its behavioral effects on hippocampal memory tasks
Program Area: Bridging Brain, Mind & Behavior
Grant Type: Collaborative Activity Award
Year Awarded: 2007
Project Summary:
A central tenet of neuroscience and clinical neurology until the end of the 20th Century held that no new neurons were generated after birth in the mammalian brain. Neurons could undergo changes through the processes of developmental maturation and aging and they could develop new functional connections (synapses), but neurons lost as a result of injury or disease could not be replaced. For humans, this meant the neurons we were born with were the only neurons we would ever have. Unlike the continual generation of cells comprising other tissues (e.g. liver or skin), brain tissue could not benefit from the continual turnover or renewal of neurons. This characteristic of neurons marked them as unique.
Challenges to the “no new neurons” dogma were published beginning in the 1940’s, but the findings were usually marginalized or ignored by the field. Beginning in the 1990’s, technical advances allowed a flurry of papers to appear reporting solid evidence that new neurons were generated in the brains of rodents and primates. In the past decade, the studies of neurogenesis have proceeded at a brisk pace. Much of the work characterizing the cellular properties of the post-natal neurons has, needless to say, been carried out with animals.
The fact that neurogenesis can occur widely in some mammalian brains while in humans it is limited to hippocampus raises a number of interesting questions about its purpose. The hippocampus is important for learning and memory and in humans it is particularly vulnerable to strokes or diseases such as Alzheimers. What is the role of these new neurons at the cellular, systems, and functional level? How are new neurons incorporated into a highly complex network comprised of hundreds of thousands of neurons making millions of connections? Are the new neurons functional on a temporary or permanent basis? What role, if any, do they play in aging or in the recovery from injury or disease? What do the species differences tell us about brain evolution? How can findings from different species such as rodents and humans best be compared? What characteristics of hippocampal structure and function permits the integration of new neurons while cortical tissue does not? Probing such questions is the goal of this international collaborative activity grant.