The hippocampus is one of the central brain regions governing our everyday lives, with its crucial role in such aspects as learning new things and navigating in different environments. The circuit wiring between the entorhinal cortex and the hippocampus provides the substrate for hippocampal function. Interestingly, the hippocampus not only has extensive plasticity, but more importantly, it retains the capability to continuously generate new neurons for the adult brain. The question that has been continuously asked is: since there are thousands of existing hippocampal neurons, why do we need new neurons? That is, do adult-born neurons exhibit any special functions? In this proposal, we attempt to address this question in two main aims: In the aim 1, we will use an in vivo imaging system we recently established to examine the activity of newborn neurons at different ages during hippocampus-based behaviors. We expect to observe newborn neurons at certain ages showing differential activation patterning, suggesting their unique role for hippocampus-based behaviors.
In Aim 2, we will activate or silence a cohort of newborn neurons and analyze the activity pattern of existing neurons. We expect to identify the circuit role of newborn neurons. Together, these tests will for the first time analyze new neurons? activation and influence on existing circuits in vivo. If successful, our findings will advance our understanding of why the adult brain needs continuous hippocampal neurogenesis. The findings will also provide insights into the understanding of hippocampal circuit activity during behavior.
Disease, degeneration or traumatic injury of the nervous system are among the greatest public health concerns in the United States and are generally considered irreparable, often causing catastrophic damage to the functional capacity of the individual. Now, however, characterization of neural stem cells residing within specific germinal centers of the brain and in cell culture raises hope that functional regeneration of nervous tissue may be feasible, if we learn to exploit adult neurogenesis for clinical benefit. The research proposal here aims to study how new brain cells in the adult brain react and respond to our daily lives. If successful, this proposal will lead to improved understanding of neural stem cell biology, possibly leading to the development of new drugs for repair and regeneration of the nervous system.
