Experience-dependent glial pruning of synaptic glomeruli during the critical period. 2024

Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
Department of Biological Sciences, Vanderbilt University and Medical Center, Nashville, TN, 37235, USA.

Critical periods are temporally-restricted, early-life windows when sensory experience remodels synaptic connectivity to optimize environmental input. In the Drosophila juvenile brain, critical period experience drives synapse elimination, which is transiently reversible. Within olfactory sensory neuron (OSN) classes synapsing onto single projection neurons extending to brain learning/memory centers, we find glia mediate experience-dependent pruning of OSN synaptic glomeruli downstream of critical period odorant exposure. We find glial projections infiltrate brain neuropil in response to critical period experience, and use Draper (MEGF10) engulfment receptors to prune synaptic glomeruli. Downstream, we find antagonistic Basket (JNK) and Puckered (DUSP) signaling is required for the experience-dependent translocation of activated Basket into glial nuclei. Dependent on this signaling, we find critical period experience drives expression of the F-actin linking signaling scaffold Cheerio (FLNA), which is absolutely essential for the synaptic glomeruli pruning. We find Cheerio mediates experience-dependent regulation of the glial F-actin cytoskeleton for critical period remodeling. These results define a sequential pathway for experience-dependent brain synaptic glomeruli pruning in a strictly-defined critical period; input experience drives neuropil infiltration of glial projections, Draper/MEGF10 receptors activate a Basket/JNK signaling cascade for transcriptional activation, and Cheerio/FLNA induction regulates the glial actin cytoskeleton to mediate targeted synapse phagocytosis.

UI MeSH Term Description Entries
D009457 Neuroglia The non-neuronal cells of the nervous system. They not only provide physical support, but also respond to injury, regulate the ionic and chemical composition of the extracellular milieu, participate in the BLOOD-BRAIN BARRIER and BLOOD-RETINAL BARRIER, form the myelin insulation of nervous pathways, guide neuronal migration during development, and exchange metabolites with neurons. Neuroglia have high-affinity transmitter uptake systems, voltage-dependent and transmitter-gated ion channels, and can release transmitters, but their role in signaling (as in many other functions) is unclear. Bergmann Glia,Bergmann Glia Cells,Bergmann Glial Cells,Glia,Glia Cells,Satellite Glia,Satellite Glia Cells,Satellite Glial Cells,Glial Cells,Neuroglial Cells,Bergmann Glia Cell,Bergmann Glial Cell,Cell, Bergmann Glia,Cell, Bergmann Glial,Cell, Glia,Cell, Glial,Cell, Neuroglial,Cell, Satellite Glia,Cell, Satellite Glial,Glia Cell,Glia Cell, Bergmann,Glia Cell, Satellite,Glia, Bergmann,Glia, Satellite,Glial Cell,Glial Cell, Bergmann,Glial Cell, Satellite,Glias,Neuroglial Cell,Neuroglias,Satellite Glia Cell,Satellite Glial Cell,Satellite Glias
D001921 Brain The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM. Encephalon
D004330 Drosophila A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology. Fruit Fly, Drosophila,Drosophila Fruit Flies,Drosophila Fruit Fly,Drosophilas,Flies, Drosophila Fruit,Fly, Drosophila Fruit,Fruit Flies, Drosophila
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D015398 Signal Transduction The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway. Cell Signaling,Receptor-Mediated Signal Transduction,Signal Pathways,Receptor Mediated Signal Transduction,Signal Transduction Pathways,Signal Transduction Systems,Pathway, Signal,Pathway, Signal Transduction,Pathways, Signal,Pathways, Signal Transduction,Receptor-Mediated Signal Transductions,Signal Pathway,Signal Transduction Pathway,Signal Transduction System,Signal Transduction, Receptor-Mediated,Signal Transductions,Signal Transductions, Receptor-Mediated,System, Signal Transduction,Systems, Signal Transduction,Transduction, Signal,Transductions, Signal
D018034 Olfactory Receptor Neurons Neurons in the OLFACTORY EPITHELIUM with proteins (RECEPTORS, ODORANT) that bind, and thus detect, odorants. These neurons send their DENDRITES to the surface of the epithelium with the odorant receptors residing in the apical non-motile cilia. Their unmyelinated AXONS synapse in the OLFACTORY BULB of the BRAIN. Neurons, Olfactory Receptor,Olfactory Receptor Cells,Olfactory Receptor Neuron,Olfactory Sensory Cells,Olfactory Sensory Cilia,Olfactory Sensory Neurons,Cell, Olfactory Receptor,Cell, Olfactory Sensory,Cells, Olfactory Receptor,Cells, Olfactory Sensory,Cilia, Olfactory Sensory,Cilias, Olfactory Sensory,Neuron, Olfactory Receptor,Neuron, Olfactory Sensory,Neurons, Olfactory Sensory,Olfactory Receptor Cell,Olfactory Sensory Cell,Olfactory Sensory Cilias,Olfactory Sensory Neuron,Receptor Cell, Olfactory,Receptor Cells, Olfactory,Receptor Neuron, Olfactory,Receptor Neurons, Olfactory,Sensory Cell, Olfactory,Sensory Cells, Olfactory,Sensory Cilia, Olfactory,Sensory Cilias, Olfactory,Sensory Neuron, Olfactory,Sensory Neurons, Olfactory
D029721 Drosophila Proteins Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development. Drosophila melanogaster Proteins,Proteins, Drosophila,Proteins, Drosophila melanogaster,melanogaster Proteins, Drosophila

Related Publications

Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
May 2024, Cellular signalling,
Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
January 2017, Cell reports,
Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
November 2017, Nature reviews. Neuroscience,
Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
February 2019, Neurobiology of disease,
Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
May 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
November 2022, Nature neuroscience,
Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
September 2009, The Journal of neuroscience : the official journal of the Society for Neuroscience,
Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
March 2021, eLife,
Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
September 2022, Biological psychiatry,
Nichalas Nelson, and Dominic J Vita, and Kendal Broadie
March 2024, Journal of visualized experiments : JoVE,
Copied contents to your clipboard!