UC San Diego

This work explores the functional role of experience dependent newborn neurons (EDNN) in the dentate gyrus of the adult mammalian hippocampus. Adult hippocampl neurogenesis is the generation of newborn neurons that occurs throughout life in mammals. EDNNs are a specific population of newborn neurons whose survival is dependent on an exposure to an enriched environment, suggesting an intimate connection between these EDNNs and the enriched environment. To probe the functional role of these EDNNs, I have employed a combination of immunohistochemistry, lentivirus mediated-knockdown, multiple enriched environments, and two commonly used hippocampus dependent behavioral tasks; the Morris watermaze and contextual fear conditioning. With the use of these methods, the work presented in this thesis provides evidence for 3 distinct functional role of EDNNs. First, EDNNs appear to play a role in the long-term memory retention of the Morris watermaze. Using a lentivirus mediated knockdown of adult neurogenesis, animals devoid of EDNNs did not exhibit a preference for the target quadrant at 1 week after training, suggesting a deficit in long-term memory. Second, EDNNs encode information specifically about previously experienced environments such that a re-exposure of the environment elicits a response by the EDNNs. By labeling two populations of EDNNs and exposing animals to two distinct enriched environments, we found that EDNNs encode information about the environment they experienced during an early critical period. Third, EDNNs are potentially involved in the ability of animals to decode their surrounding environment. When subjected to a more difficult, contextual fear conditioning paradigm, where animals are given extremely small amounts of time to explore the context, enriched animals are able to discriminate between two different contexts better than controls. This phenotype suggests that enriched animals are better at deciphering their surroundings than control animal, indicating a possible relationship between EDNNs and the ability of animals to decode their environment. The work presented in this thesis provide evidence for a functional role of EDNNs in how they benefit the animal through its ability to remember old experiences and encode new and novel ones