Cargando…

Pannexin 1 Regulates Network Ensembles and Dendritic Spine Development in Cortical Neurons

Dendritic spines are the postsynaptic targets of excitatory synaptic inputs that undergo extensive proliferation and maturation during the first postnatal month in mice. However, our understanding of the molecular mechanisms that regulate spines during this critical period is limited. Previous work...

Descripción completa

Detalles Bibliográficos
Autores principales: Sanchez-Arias, Juan C., Liu, Mei, Choi, Catherine S. W., Ebert, Sarah N., Brown, Craig E., Swayne, Leigh Anne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557035/
https://www.ncbi.nlm.nih.gov/pubmed/31118206
http://dx.doi.org/10.1523/ENEURO.0503-18.2019
_version_ 1783425411806396416
author Sanchez-Arias, Juan C.
Liu, Mei
Choi, Catherine S. W.
Ebert, Sarah N.
Brown, Craig E.
Swayne, Leigh Anne
author_facet Sanchez-Arias, Juan C.
Liu, Mei
Choi, Catherine S. W.
Ebert, Sarah N.
Brown, Craig E.
Swayne, Leigh Anne
author_sort Sanchez-Arias, Juan C.
collection PubMed
description Dendritic spines are the postsynaptic targets of excitatory synaptic inputs that undergo extensive proliferation and maturation during the first postnatal month in mice. However, our understanding of the molecular mechanisms that regulate spines during this critical period is limited. Previous work has shown that pannexin 1 (Panx1) regulates neurite growth and synaptic plasticity. We therefore investigated the impact of global Panx1 KO on spontaneous cortical neuron activity using Ca(2+) imaging and in silico network analysis. Panx1 KO increased both the number and size of spontaneous co-active cortical neuron network ensembles. To understand the basis for these findings, we investigated Panx1 expression in postnatal synaptosome preparations from early postnatal mouse cortex. Between 2 and 4 postnatal weeks, we observed a precipitous drop in cortical synaptosome protein levels of Panx1, suggesting it regulates synapse proliferation and/or maturation. At the same time points, we observed significant enrichment of the excitatory postsynaptic density proteins PSD-95, GluA1, and GluN2a in cortical synaptosomes from global Panx1 knock-out mice. Ex vivo analysis of pyramidal neuron structure in somatosensory cortex revealed a consistent increase in dendritic spine densities in both male and female Panx1 KO mice. Similar findings were observed in an excitatory neuron-specific Panx1 KO line (Emx1-Cre driven; Panx1 cKO(E)) and in primary Panx1 KO cortical neurons cultured in vitro. Altogether, our study suggests that Panx1 negatively regulates cortical dendritic spine development.
format Online
Article
Text
id pubmed-6557035
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Society for Neuroscience
record_format MEDLINE/PubMed
spelling pubmed-65570352019-06-10 Pannexin 1 Regulates Network Ensembles and Dendritic Spine Development in Cortical Neurons Sanchez-Arias, Juan C. Liu, Mei Choi, Catherine S. W. Ebert, Sarah N. Brown, Craig E. Swayne, Leigh Anne eNeuro New Research Dendritic spines are the postsynaptic targets of excitatory synaptic inputs that undergo extensive proliferation and maturation during the first postnatal month in mice. However, our understanding of the molecular mechanisms that regulate spines during this critical period is limited. Previous work has shown that pannexin 1 (Panx1) regulates neurite growth and synaptic plasticity. We therefore investigated the impact of global Panx1 KO on spontaneous cortical neuron activity using Ca(2+) imaging and in silico network analysis. Panx1 KO increased both the number and size of spontaneous co-active cortical neuron network ensembles. To understand the basis for these findings, we investigated Panx1 expression in postnatal synaptosome preparations from early postnatal mouse cortex. Between 2 and 4 postnatal weeks, we observed a precipitous drop in cortical synaptosome protein levels of Panx1, suggesting it regulates synapse proliferation and/or maturation. At the same time points, we observed significant enrichment of the excitatory postsynaptic density proteins PSD-95, GluA1, and GluN2a in cortical synaptosomes from global Panx1 knock-out mice. Ex vivo analysis of pyramidal neuron structure in somatosensory cortex revealed a consistent increase in dendritic spine densities in both male and female Panx1 KO mice. Similar findings were observed in an excitatory neuron-specific Panx1 KO line (Emx1-Cre driven; Panx1 cKO(E)) and in primary Panx1 KO cortical neurons cultured in vitro. Altogether, our study suggests that Panx1 negatively regulates cortical dendritic spine development. Society for Neuroscience 2019-06-06 /pmc/articles/PMC6557035/ /pubmed/31118206 http://dx.doi.org/10.1523/ENEURO.0503-18.2019 Text en Copyright © 2019 Sanchez-Arias et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle New Research
Sanchez-Arias, Juan C.
Liu, Mei
Choi, Catherine S. W.
Ebert, Sarah N.
Brown, Craig E.
Swayne, Leigh Anne
Pannexin 1 Regulates Network Ensembles and Dendritic Spine Development in Cortical Neurons
title Pannexin 1 Regulates Network Ensembles and Dendritic Spine Development in Cortical Neurons
title_full Pannexin 1 Regulates Network Ensembles and Dendritic Spine Development in Cortical Neurons
title_fullStr Pannexin 1 Regulates Network Ensembles and Dendritic Spine Development in Cortical Neurons
title_full_unstemmed Pannexin 1 Regulates Network Ensembles and Dendritic Spine Development in Cortical Neurons
title_short Pannexin 1 Regulates Network Ensembles and Dendritic Spine Development in Cortical Neurons
title_sort pannexin 1 regulates network ensembles and dendritic spine development in cortical neurons
topic New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6557035/
https://www.ncbi.nlm.nih.gov/pubmed/31118206
http://dx.doi.org/10.1523/ENEURO.0503-18.2019
work_keys_str_mv AT sanchezariasjuanc pannexin1regulatesnetworkensemblesanddendriticspinedevelopmentincorticalneurons
AT liumei pannexin1regulatesnetworkensemblesanddendriticspinedevelopmentincorticalneurons
AT choicatherinesw pannexin1regulatesnetworkensemblesanddendriticspinedevelopmentincorticalneurons
AT ebertsarahn pannexin1regulatesnetworkensemblesanddendriticspinedevelopmentincorticalneurons
AT browncraige pannexin1regulatesnetworkensemblesanddendriticspinedevelopmentincorticalneurons
AT swayneleighanne pannexin1regulatesnetworkensemblesanddendriticspinedevelopmentincorticalneurons