Anatomical, molecular, and physiological interactions between astrocytes and neuronal synapses regulate information processing in the brain. The fruit fly Drosophila melanogaster has become a valuable experimental system for genetic manipulation of the nervous system and has enormous potential for elucidating mechanisms that mediate neuron glia interactions. Here, we show the first electrophysiological recordings from Drosophila astrocytes and characterize their spatial and physiological relationship with particular synapses. Astrocyte intrinsic properties were found to be strongly analogous to those of vertebrate astrocytes, including a passive current-voltage relationship, low membrane resistance, high capacitance, and dye-coupling to local astrocytes. Responses to optogenetic stimulation of glutamatergic pre-motor neurons were correlated directly with anatomy using serial electron microscopy reconstructions of homologous identified neurons and surrounding astrocytic processes. Robust bidirectional communication was present: neuronal activation triggered astrocytic glutamate transport via Eaat1, and blocking Eaat1 extended glutamatergic interneuron-evoked inhibitory post-synaptic currents in motor neurons. The neuronal synapses were always located within a micron of an astrocytic process, but none were ensheathed by those processes. Thus, fly astrocytes can modulate fast synaptic transmission via neurotransmitter transport within these anatomical parameters.
Anatomical, molecular, and physiological interactions between astrocytes and neuronal synapses regulate information processing in the brain. The fruit fly Drosophila melanogaster has become a valuable experimental system for genetic manipulation of the nervous system and has enormous potential for elucidating mechanisms that mediate neuron glia interactions. Here, we show the first electrophysiological recordings from Drosophila astrocytes and characterize their spatial and physiological relationship with particular synapses. Astrocyte intrinsic properties were found to be strongly analogous to those of vertebrate astrocytes, including a passive current-voltage relationship, low membrane resistance, high capacitance, and dye-coupling to local astrocytes. Responses to optogenetic stimulation of glutamatergic pre-motor neurons were correlated directly with anatomy using serial electron microscopy reconstructions of homologous identified neurons and surrounding astrocytic processes. Robust bidirectional communication was present: neuronal activation triggered astrocytic glutamate transport via Eaat1, and blocking Eaat1 extended glutamatergic interneuron-evoked inhibitory post-synaptic currents in motor neurons. The neuronal synapses were always located within a micron of an astrocytic process, but none were ensheathed by those processes. Thus, fly astrocytes can modulate fast synaptic transmission via neurotransmitter transport within these anatomical parameters. Graphical AbstractCorresponding Author: Sarah E. MacNamee, University of Arizona Dept. of Neuroscience, 1040 E 4 th St GS Rm 611, Tucson AZ 85721, (520) 621 6671, Smac3@email.arizona.edu. Role of AuthorsAll authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: SEM, LAO. Acquisition of data: SEM, KEL, SG, CTT, RDF, AC. Analysis and interpretation of data: SEM, KEL, CTT. Drafting of the manuscript: SEM. Critical revision of the manuscript for important intellectual content: LAO, LPT, AC. Statistical analysis: SEM. Obtained funding: LAO, LPT, AC. Administrative, technical, and material support: none. Study supervision: LAO, LPT. Conflict of Interest StatementThe authors have no conflict of interest to disclose. Data AccessibilityData generated in the lab and the subsequent analyses will be made available upon request to the Oland/Tolbert laboratory by qualified individuals as long as doing so would not compromise intellectual property interests or interfere with publication. Any shared data would include notations, standards, and the like that are necessary for interpretation of the data. HHMI Author Manuscript HHMI Author Manuscript HHMI Author ManuscriptThe authors show the first recordings from Drosophila astrocytes and find that their electrophysiological properties are strongly analogous to those of vertebrate astrocytes. Using correlative electron microscopy and physiology, they found no glial ensheathment of glutamatergic synap...
Neurodevelopment and efferocytosis have fascinated scientists for decades. How an organism builds a nervous system that is precisely tuned for efficient behaviors and survival and how it simultaneously manages constant somatic cell turnover are complex questions that have resulted in distinct fields of study. Although neurodevelopment requires the overproduction of cells that are subsequently pruned back, very few studies marry these fields to elucidate the cellular and molecular mechanisms that drive nervous system development through the lens of cell clearance. In this review, we discuss these fields to highlight exciting areas of future synergy. We first review neurodevelopment from the perspective of overproduction and subsequent refinement and then discuss who clears this developmental debris and the mechanisms that control these events. We then end with how a more deliberate merger of neurodevelopment and efferocytosis could reframe our understanding of homeostasis and disease and discuss areas of future study. Expected final online publication date for the Annual Review of Neuroscience, Volume 45 is July 2022. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
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