Circuits made-up of neurons are responsible for the unique qualities of the brain: perception, memory, abstraction and control of behavior. We are interested in how neurons are formed and become integrated into neural circuits. Neurons are generally thought to be produced early in development, live a long time and never be replaced. For many types of neuronal circuits this may be the case, but it is not true for all of them. Neurons in certain parts of the brain are replaced throughout life. Taking advantage of the late generation of some types of neurons we address fundamental questions about the mechanism of neuronal birth, migration and differentiation. In addition, we are interested in how new nerve cells are integrated and contribute to the function adult brain circuits. Work in our laboratory identified a region in the brain of adult mammals, close to the walls of the lateral ventricles, containing large numbers of neuronal precursors. Subsequently, we demonstrated that young neurons born in this brain region, migrate a long distance through the anterior forebrain to complete their differentiation and become integrated in the olfactory bulb. This migration happens constantly and at a very high rate. Further work on this system led us to identify a novel form of neuronal translocation, called chain migration. This migration is unique in that young neurons move without the aid of radial glial or axonal guides. Instead, young neurons migrate closely associated to each other, forming long aggregates called chains. We have shown that there is a very extensive network of chains of young migrating neurons in the adult brain. Most recently we have identified the stem cells that give rise to the new neurons in the SVZ. Surprisingly, these cells correspond to astrocytes.

What is the mechanism of chain migration? We would like to understand how neuronal precursors become organized into chains, how cells move in chains, what guides young neurons toward the olfactory bulb and where else in the adult and embryonic brain chain migration occurs.

What kinds of astrocytes can function as stem cells? We are in search for better marker, in the embryo and in the adult, for neural stem cells. We are studying the molecular signals that regulate the proliferation and differentiation of neural stem cells.

What is the function of neurons formed in the adult brain and how do olfactory learning and olfactory discrimination affect neuronal recruitment in the olfactory bulb? We are interested in behavioral or hormonal conditions that affect neuronal replacement in the olfactory bulb. In parallel we are developing techniques to stop neuronal production or migration to study their effects on the olfactory bulb and olfactory function.

What is the relationship of neural stem cells to brain tumors? We are trying to test whether brain tumors originate from the astrocytes that function as stem cells in the adult brain.

The adult brain offers unique advantages to study the mechanism of neuronal production, migration and differentiation: germinal layers contain many fewer cells and are simpler in organization as compared to the embryo; neuronal production is not limited to a short window of time, but occurs over long periods; cell movements are not affected by major changes in brain structure; cells can be grafted into precise locations in the germinal layers. In addition, experimental manipulation of neuronal production, migration or survival in juveniles and adults will allow us to ask questions about the contribution of specific types of neurons to behavior and brain repair.