Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic Inactivity

The morphology and function of neuronal synapses are regulated by neural activity, as manifested in activity-dependent synapse maturation and various forms of synaptic plasticity. Here we employed cryo-electron tomography (cryo-ET) to visualize synaptic ultrastructure in cultured hippocampal neurons...

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Main Authors: Chang-Lu Tao, Yun-Tao Liu, Z. Hong Zhou, Pak-Ming Lau, Guo-Qiang Bi
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-06-01
Series:Frontiers in Neuroanatomy
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fnana.2018.00048/full
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author Chang-Lu Tao
Chang-Lu Tao
Chang-Lu Tao
Yun-Tao Liu
Yun-Tao Liu
Yun-Tao Liu
Z. Hong Zhou
Z. Hong Zhou
Z. Hong Zhou
Z. Hong Zhou
Pak-Ming Lau
Pak-Ming Lau
Pak-Ming Lau
Guo-Qiang Bi
Guo-Qiang Bi
Guo-Qiang Bi
Guo-Qiang Bi
author_facet Chang-Lu Tao
Chang-Lu Tao
Chang-Lu Tao
Yun-Tao Liu
Yun-Tao Liu
Yun-Tao Liu
Z. Hong Zhou
Z. Hong Zhou
Z. Hong Zhou
Z. Hong Zhou
Pak-Ming Lau
Pak-Ming Lau
Pak-Ming Lau
Guo-Qiang Bi
Guo-Qiang Bi
Guo-Qiang Bi
Guo-Qiang Bi
author_sort Chang-Lu Tao
collection DOAJ
description The morphology and function of neuronal synapses are regulated by neural activity, as manifested in activity-dependent synapse maturation and various forms of synaptic plasticity. Here we employed cryo-electron tomography (cryo-ET) to visualize synaptic ultrastructure in cultured hippocampal neurons and investigated changes in subcellular features in response to chronic inactivity, a paradigm often used for the induction of homeostatic synaptic plasticity. We observed a more than 2-fold increase in the mean number of dense core vesicles (DCVs) in the presynaptic compartment of excitatory synapses and an almost 20-fold increase in the number of DCVs in the presynaptic compartment of inhibitory synapses after 2 days treatment with the voltage-gated sodium channel blocker tetrodotoxin (TTX). Short-term treatment with TTX and the N-methyl-D-aspartate receptor (NMDAR) antagonist amino-5-phosphonovaleric acid (AP5) caused a 3-fold increase in the number of DCVs within 100 nm of the active zone area in excitatory synapses but had no significant effects on the overall number of DCVs. In contrast, there were very few DCVs in the postsynaptic compartments of both synapse types under all conditions. These results are consistent with a role for presynaptic DCVs in activity-dependent synapse maturation. We speculate that these accumulated DCVs can be released upon reactivation and may contribute to homeostatic metaplasticity.
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spelling doaj.art-df7ee0c8fc4047d49115bb4a6ebed98f2022-12-22T03:09:11ZengFrontiers Media S.A.Frontiers in Neuroanatomy1662-51292018-06-011210.3389/fnana.2018.00048369322Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic InactivityChang-Lu Tao0Chang-Lu Tao1Chang-Lu Tao2Yun-Tao Liu3Yun-Tao Liu4Yun-Tao Liu5Z. Hong Zhou6Z. Hong Zhou7Z. Hong Zhou8Z. Hong Zhou9Pak-Ming Lau10Pak-Ming Lau11Pak-Ming Lau12Guo-Qiang Bi13Guo-Qiang Bi14Guo-Qiang Bi15Guo-Qiang Bi16Center for Integrative Imaging, National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei, ChinaCAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, ChinaCenter for Integrative Imaging, National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei, ChinaCAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, ChinaCenter for Integrative Imaging, National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei, ChinaThe California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, United StatesDepartment of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, Los Angeles, CA, United StatesCenter for Integrative Imaging, National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei, ChinaCAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, ChinaCenter for Integrative Imaging, National Laboratory for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, ChinaSchool of Life Sciences, University of Science and Technology of China, Hefei, ChinaCAS Key Laboratory of Brain Function and Disease, University of Science and Technology of China, Hefei, ChinaCAS Center for Excellence in Brain Science and Intelligence Technology, University of Science and Technology of China, Hefei, ChinaThe morphology and function of neuronal synapses are regulated by neural activity, as manifested in activity-dependent synapse maturation and various forms of synaptic plasticity. Here we employed cryo-electron tomography (cryo-ET) to visualize synaptic ultrastructure in cultured hippocampal neurons and investigated changes in subcellular features in response to chronic inactivity, a paradigm often used for the induction of homeostatic synaptic plasticity. We observed a more than 2-fold increase in the mean number of dense core vesicles (DCVs) in the presynaptic compartment of excitatory synapses and an almost 20-fold increase in the number of DCVs in the presynaptic compartment of inhibitory synapses after 2 days treatment with the voltage-gated sodium channel blocker tetrodotoxin (TTX). Short-term treatment with TTX and the N-methyl-D-aspartate receptor (NMDAR) antagonist amino-5-phosphonovaleric acid (AP5) caused a 3-fold increase in the number of DCVs within 100 nm of the active zone area in excitatory synapses but had no significant effects on the overall number of DCVs. In contrast, there were very few DCVs in the postsynaptic compartments of both synapse types under all conditions. These results are consistent with a role for presynaptic DCVs in activity-dependent synapse maturation. We speculate that these accumulated DCVs can be released upon reactivation and may contribute to homeostatic metaplasticity.https://www.frontiersin.org/article/10.3389/fnana.2018.00048/fullsynaptic structuredense core vesiclehomeostatic plasticitycryo-electron tomographytetrodotoxin
spellingShingle Chang-Lu Tao
Chang-Lu Tao
Chang-Lu Tao
Yun-Tao Liu
Yun-Tao Liu
Yun-Tao Liu
Z. Hong Zhou
Z. Hong Zhou
Z. Hong Zhou
Z. Hong Zhou
Pak-Ming Lau
Pak-Ming Lau
Pak-Ming Lau
Guo-Qiang Bi
Guo-Qiang Bi
Guo-Qiang Bi
Guo-Qiang Bi
Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic Inactivity
Frontiers in Neuroanatomy
synaptic structure
dense core vesicle
homeostatic plasticity
cryo-electron tomography
tetrodotoxin
title Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic Inactivity
title_full Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic Inactivity
title_fullStr Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic Inactivity
title_full_unstemmed Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic Inactivity
title_short Accumulation of Dense Core Vesicles in Hippocampal Synapses Following Chronic Inactivity
title_sort accumulation of dense core vesicles in hippocampal synapses following chronic inactivity
topic synaptic structure
dense core vesicle
homeostatic plasticity
cryo-electron tomography
tetrodotoxin
url https://www.frontiersin.org/article/10.3389/fnana.2018.00048/full
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