From Neural Stem Cells to Functional Neurons in the Adult Hippocampus

ALEJANDRO F. SCHINDER

Simposio; Keystone Symposium; 2011

Keystone Symposia

Neural stem cells of the adult hippocampus generate functional neurons that are fully capable of information processing and are required for learning, memory and behaviors involving the hippocampal formation. Yet, the functional significance of adult neurogenesis remains largely unclear. What makes newly generated neurons relevant in the dentate gyrus network? We have previously shown that, when fully mature, adult-born neurons are very similar to preexisting neurons born during perinatal development. However, newborn cells are unique before reaching a mature stage. Immature neurons exhibit high excitability, reduced inhibition and enhanced synaptic plasticity, which would allow them to process information in a distinct fashion compared to all mature neurons in the preexisting circuit. The duration and the impact of those distinctive functional properties in the dentate gyrus network depend on the speed of maturation of new neurons, a parameter that has remained largely unexplored. We have recently observed that the time window during which newborn neurons remain immature is highly plastic and display striking differences along the septo-temporal axis of the hippocampus. We found a faster rate of neuronal maturation in the granule cell layer of the septal region that is associated to higher levels of basal activity, while slow maturation and lower activity were seen in the temporal dentate gyrus. Interestingly, voluntary exercise increased basal activity in the temporal region and accelerated neuronal development in that area. These variable rates of neuronal maturation have functional implications for the encoding of episodic memory. The mechanisms underlying this novel type of activity-dependent plasticity acting on neuronal maturation are currently under investigation.