Genetic control of astrocyte function in neural circuits.
During the last two decades numerous genetic approaches affecting cell function in vivo have been developed. Current state-of-the-art technology permits the selective switching of gene function in distinct cell populations within the complex organization of a given tissue parenchyma. The tamoxifen-inducible Cre/loxP gene recombination and the doxycycline-dependent modulation of gene expression are probably the most popular genetic paradigms. Here, we will review applications of these two strategies while focusing on the interactions of astrocytes and neurons in the central nervous system (CNS) and their impact for the whole organism. Abolishing glial sensing of neuronal activity by selective deletion of glial transmitter receptors demonstrated the impact of astrocytes for higher cognitive functions such as learning and memory, or the more basic body control of muscle coordination. Interestingly, also interfering with glial output, i.e., the release of gliotransmitters can drastically change animal's physiology like sleeping behavior. Furthermore, such genetic approaches have also been used to restore astrocyte function. In these studies two alternatives were employed to achieve proper genetic targeting of astrocytes: transgenes using the promoter of the human glial fibrillary acidic protein (GFAP) or homologous recombination into the glutamate-aspartate transporter (GLAST) locus. We will highlight their specific properties that could be relevant for their use.
Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland Homburg, Germany.
Hannah M
HM
Jahn
Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland Homburg, Germany.
Anja
A
Scheller
Molecular Physiology, Center for Integrative Physiology and Molecular Medicine (CIPMM), University of Saarland Homburg, Germany.
Frank
F
Kirchhoff
Bergmann glia; CreERT2/loxP; GLAST glutamate aspartate transporter; genetic targeting of astrocytes; human GFAP promoter; tamoxifen