Investigating Astrocyte Diversity and Function in Midbrain Dopaminergic Circuits

University Of California, San Francisco, San Francisco CA

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Abstract

Enter the text here that is the new abstract information for your application. This section must be no longer than 30 lines of text. ABSTRACT Recent studies indicate that astrocytes are spatially diversified, which may have consequence for psychiatric diseases with regional brain dysfunction. However, establishing diversified functions of astrocytes in brain development and disease has been limited by a lack of tools for lineage-specific astrocyte manipulation. Recently, we developed novel transgenic methods to label, purify and characterize regional astrocyte populations in mouse brain. The midbrain and brainstem contain dopaminergic nuclei of the ventral tegmental area (VTA) and substantia nigra (SN) that are implicated in schizophrenia, ADHD and Parkinson's disease. We will test the hypothesis that regionally-specified astrocytes from the ventral midbrain are uniquely suited to support survival and connectivity of dopaminergic projections from the VTA and SN. We will determine molecular diversity of region-restricted midbrain astrocytes as a first step towards uncovering the role of regionally diverse astrocytes in neurological disorders. Deliverables include validated transgenic mouse tools for conditional temporal- spatial labeling, purification of astrocytes throughout the CNS as well as markers of regionally heterogeneous astrocytes subtypes of mid/hindbrain compiled into a public database. The project is intended to reveal signatures of astrocyte subtypes and provide insight into the role of astrocytes in mental health.