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Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles
Accumulating evidence indicate that GABA regulates activity-dependent development of inhibitory synapses in the vertebrate brain, but the underlying mechanisms remain unclear. Here we combined live imaging of cortical GABAergic axons with single cell genetic manipulation to dissect the role of presy...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3512030/ https://www.ncbi.nlm.nih.gov/pubmed/23227002 http://dx.doi.org/10.3389/fncel.2012.00057 |
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author | Fu, Yu Wu, Xiaoyun Lu, Jiangteng Huang, Z. Josh |
author_facet | Fu, Yu Wu, Xiaoyun Lu, Jiangteng Huang, Z. Josh |
author_sort | Fu, Yu |
collection | PubMed |
description | Accumulating evidence indicate that GABA regulates activity-dependent development of inhibitory synapses in the vertebrate brain, but the underlying mechanisms remain unclear. Here we combined live imaging of cortical GABAergic axons with single cell genetic manipulation to dissect the role of presynaptic GABA(B) receptors (GABA(B)Rs) in inhibitory synapse formation in mouse. Developing GABAergic axons form a significant number of transient boutons but only a subset was stabilized. Synaptic vesicles in these nascent boutons are often highly mobile in the course of tens of minutes. Activation of presynaptic GABA(B)Rs stabilized mobile vesicles in nascent boutons through the local enhancement of actin polymerization. Inactivation of GABA(B)Rs in developing basket interneurons resulted in aberrant pattern of bouton size distribution, reduced bouton density and reduced axon branching, as well as reduced frequency of miniature inhibitory currents in postsynaptic pyramidal neurons. These results suggest that GABA(B)Rs along developing inhibitory axons act as a local sensor of GABA release and promote presynaptic maturation through increased recruitment of mobile vesicle pools. Such release-dependent validation and maturation of nascent terminals is well suited to sculpt the pattern of synapse formation and distribution along axon branches. |
format | Online Article Text |
id | pubmed-3512030 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-35120302012-12-07 Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles Fu, Yu Wu, Xiaoyun Lu, Jiangteng Huang, Z. Josh Front Cell Neurosci Neuroscience Accumulating evidence indicate that GABA regulates activity-dependent development of inhibitory synapses in the vertebrate brain, but the underlying mechanisms remain unclear. Here we combined live imaging of cortical GABAergic axons with single cell genetic manipulation to dissect the role of presynaptic GABA(B) receptors (GABA(B)Rs) in inhibitory synapse formation in mouse. Developing GABAergic axons form a significant number of transient boutons but only a subset was stabilized. Synaptic vesicles in these nascent boutons are often highly mobile in the course of tens of minutes. Activation of presynaptic GABA(B)Rs stabilized mobile vesicles in nascent boutons through the local enhancement of actin polymerization. Inactivation of GABA(B)Rs in developing basket interneurons resulted in aberrant pattern of bouton size distribution, reduced bouton density and reduced axon branching, as well as reduced frequency of miniature inhibitory currents in postsynaptic pyramidal neurons. These results suggest that GABA(B)Rs along developing inhibitory axons act as a local sensor of GABA release and promote presynaptic maturation through increased recruitment of mobile vesicle pools. Such release-dependent validation and maturation of nascent terminals is well suited to sculpt the pattern of synapse formation and distribution along axon branches. Frontiers Media S.A. 2012-12-03 /pmc/articles/PMC3512030/ /pubmed/23227002 http://dx.doi.org/10.3389/fncel.2012.00057 Text en Copyright © 2012 Fu, Wu, Lu and Huang. http://www.frontiersin.org/licenseagreement This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in other forums, provided the original authors and source are credited and subject to any copyright notices concerning any third-party graphics etc. |
spellingShingle | Neuroscience Fu, Yu Wu, Xiaoyun Lu, Jiangteng Huang, Z. Josh Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles |
title | Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles |
title_full | Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles |
title_fullStr | Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles |
title_full_unstemmed | Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles |
title_short | Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles |
title_sort | presynaptic gaba(b) receptor regulates activity-dependent maturation and patterning of inhibitory synapses through dynamic allocation of synaptic vesicles |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3512030/ https://www.ncbi.nlm.nih.gov/pubmed/23227002 http://dx.doi.org/10.3389/fncel.2012.00057 |
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