Neurogenesis in the Neocortex of the Adult Macaque and its Modulation by Experience

A traditional view of the organization of the mammalian brain is that no neurons are formed in adulthood. This view has been challenged in the last decade by the finding of neurogenesis (the formation of new neurons) in the hippocampal formation of a variety of species. Although the significance of adult neurogenesis in the hippocampus is essentially unknown, some evidence suggests that the incidence of new neurons may be affected by the animal's experience.

Our respective laboratories, one devoted to the cognitive functions of cortex and one studying adult neurogenesis, have recently joined forces to explore the cognitive functions of neurogenesis in adult primates. In our initial collaborative effort, we demonstrated, for the first time, neurogenesis in the dentate gyrus of adult Old World monkeys. The new neurons were identified by the incorporation of the thymidine analog bromodeoxyuridine (BrdU) and by the expression of several morphological and biochemical characteristics of neurons. In our second collaborative effort we found that thousands of new neurons are added every day to two "association" areas of the neocortex of the adult macaque, prefrontal and inferior temporal cortex. This was the first demonstration of neurogenesis in any neocortex in any adult animal. By contrast, new neurons were not found in a primary sensory area, striate cortex.

Prefrontal and inferior temporal cortex are both crucially involved in the processing and storage of new information. We believe that our finding of a continual flow of new neurons to these areas may help reveal how these brain regions carry out these functions and, perhaps more generally, how experience sculpts the brain in a lasting fashion.

We propose to continue our collaboration along two general lines. First, we will determine the time course of the generation and migration of new neurons, survey their distribution in the neocortical mantle, and specify their efferent and afferent connections. The distribution of new neocortical neurons and their connections may yield clues about their functions in cognition and memory and set the stage for our next series of studies.

In the second series of experiments, we will study the effect of specific cognitive experiences on the proliferation, migration, and survival of new neurons in the neocortex. Monkeys will be trained on delayed response, a task which requires lateral frontal cortex, on visual discrimination tasks which require inferior temporal cortex, and on a control task which requires neither cortical area. We will then assess the effect of these experiences on the distribution of new neocortical neurons. In subsequent studies we will investigate the cognitive consequences of interfering with the production of new neocortical neurons.

Our findings of neurogenesis in the adult monkey appear to have implications for understanding the effects of experience on brain structure. The proposed grant will help us explore these implications.