Adult neurogenesis in the mammalian brain represents an extraordinary example of continued cellular and structural neuronal plasticity. Although the adult-born neurons have a well-defined developmental pattern, the molecular and genetic mechanisms that guide adult-born neuron synapse formation, synapse maintenance, and circuit integration are not well understood. Continued adult neurogenesis exists in two areas of the brain: the subgranular layer of the dentate gyrus in the hippocampus and the subventricular zone (SVZ) of the olfactory system. Multiple forms of activity, relayed to adult-born neurons through presynaptic inputs, have been shown affect the proliferation, survival, and synapse formation of adult-born neurons. However, the nature of how these presynaptic inputs translates to the adult-born neurons remains unknown. Transsynaptic viral circuit tracing through engineered Rabies Virus (RV) and mouse genetics was used to elucidate the cell types that provide presynaptic inputs to adult-born neurons. Numerous direct contacts were seen between adult-born neurons and local resident astrocytes. Astrocytes have recently been implemented in neuromodulation through the release of gliotransmitters known to affect neurons. Defective astrocytes have been implicated in a wide range of conditions such as Alzheimer's disease, schizophrenia, epilepsy, and tumorigenesis. Through use of genetic manipulations, local astrocytes in the olfactory bulb were manipulated to elucidate the functional role of astrocyte inputs onto adult-born neurons, leading to the hypothesis that specific local astrocyte populations play essential roles in adult-born neuron synapse formation and circuit integration in the olfactory bulb. Elucidating the molecular and cellular interactions between neurons and astrocytes that influence postnatal synaptogenesis and circuit integration will enhance our understanding of circuit formation in the developing, aging, and diseased brain. Uncovering novel functional roles for astrocytes toward adult-born neurons may not only better inform us of normal neural development and brain function, but also help explain how defects in astrocytes may contribute to neurodegenerative diseases.

F31NS089178

2014-06-01

2017-05-31