TY - JOUR T1 - Pannexin 1 regulates network ensembles and dendritic spine development in cortical neurons JF - eneuro JO - eNeuro DO - 10.1523/ENEURO.0503-18.2019 SP - ENEURO.0503-18.2019 AU - Juan C. Sanchez-Arias AU - Mei Liu AU - Catherine S.W. Choi AU - Sarah N. Ebert AU - Craig E. Brown AU - Leigh Anne Swayne Y1 - 2019/05/22 UR - http://www.eneuro.org/content/early/2019/05/22/ENEURO.0503-18.2019.abstract N2 - Dendritic spines are the post-synaptic 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 Ca2+ 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 knockout 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 cKOE) and in primary Panx1 KO cortical neurons cultured in vitro. Altogether, our study suggests that Panx1 negatively regulates cortical dendritic spine development.Significance Statement Our findings reveal an important regulatory role for Pannexin 1 (Panx1) in the formation of connections between nerve cells. We found that removal of the Panx1 altered the ability of nerve cells from the cerebral cortex to fire together. We studied the impact of removing Panx1 on the formation of 'dendritic spines', which are microscopic protrusions that receive information from other nerve cells. We found that removing Panx1 increased the expression of proteins involved in dendritic spine function and also increased the density of dendritic spines on nerve cells of the cerebral cortex. Together these findings suggest Panx1 is a 'brake' on the development of dendritic spines with important implications for the development of nerve cell connections. ER -