{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T05:25:20Z","timestamp":1776403520776,"version":"3.51.2"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T00:00:00Z","timestamp":1657065600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000001","name":"National Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000001","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>The endocrine cells of the anterior pituitary gland are electrically active when stimulated or, in some cases, when not inhibited. The activity pattern thought to be most effective in releasing hormones is bursting, which consists of depolarization with small spikes that are much longer than single spikes. Although a majority of the research on cellular activity patterns has been performed on dispersed cells, the environment <jats:italic>in situ<\/jats:italic> is characterized by networks of coupled cells of the same type, at least in the case of somatotrophs and lactotrophs. This produces some degree of synchronization of their activity, which can be greatly increased by hormones and changes in the physiological state. In this computational study, we examine how electrical coupling among model cells influences synchronization of bursting oscillations among the population. We focus primarily on weak electrical coupling, since strong coupling leads to complete synchronization that is not characteristic of pituitary cell networks. We first look at small networks to point out several unexpected behaviors of the coupled system, and then consider a larger random scale-free network to determine what features of the structural network formed through gap junctional coupling among cells produce a high degree of functional coupling, i.e., clusters of synchronized cells. We employ several network centrality measures, and find that cells that are closely related in terms of their closeness centrality are most likely to be synchronized. We also find that structural hubs (cells with extensive coupling to other cells) are typically not functional hubs (cells synchronized with many other cells). Overall, in the case of weak electrical coupling, it is hard to predict the functional network that arises from a structural network, or to use a functional network as a means for determining the structural network that gives rise to it.<\/jats:p>","DOI":"10.3389\/fendo.2022.936160","type":"journal-article","created":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T17:11:05Z","timestamp":1657127465000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Network Properties of Electrically Coupled Bursting Pituitary Cells"],"prefix":"10.3389","volume":"13","author":[{"given":"Mehran","family":"Fazli","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Bertram","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.21-16-05902.2001","article-title":"Paradoxical Role of Large-Conductance Calcium-Activated K+ (BK) Channels in Controlling Action Potential-Driven Ca2+","volume":"21","author":"Goor","year":"2001","journal-title":"J Neurosci"},{"key":"B2","doi-asserted-by":"publisher","first-page":"845","DOI":"10.1210\/er.2010-0005","article-title":"Ion Channels and Signaling in the Pituitary Gland","volume":"31","author":"Stojilkovic","year":"2010","journal-title":"Endocr Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00500.2015","article-title":"Is Bursting More Effective Than Spiking in Evoking Pituitary Hormone Secretion? A Spatiotemporal Simulation Study of Calcium and Granule Dynamics","volume":"310","author":"Tagliavini","year":"2016","journal-title":"Am J Physiol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M105386200","article-title":"Dependence of Pituitary Hormone Secretion on the Pattern of Spontaneus Voltage-Gated Calcium Influx. Cell Type-Specific Action Potential Secretion Coupling","volume":"276","author":"Van Goor","year":"2001","journal-title":"J Biol Chem"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/S1043-2760(96)00189-0","article-title":"GnRH-Induced Calcium and Current Oscillations in Gonadotrophs","volume":"7","author":"Stojilkovic","year":"1996","journal-title":"Trends Endocrin Met"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1113\/JP282367","article-title":"Chronic Stress Facilitates Bursting Electrical Activity in Pituitary Corticotrophs","volume":"600","author":"Duncan","year":"2022","journal-title":"J Physiol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"103128","DOI":"10.1063\/5.0059338","article-title":"Fast-Slow Analysis of a Stochastic Mechanism for Electrical Bursting","volume":"31","author":"Fazli","year":"2021","journal-title":"Chaos"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.3235-11.2011","article-title":"Fast-Activating Voltage- and Calcium-Dependent Potassium (BK) Conductance Promotes Bursting in Pituitary Cells: A Dynamic Clamp Study","volume":"31","author":"Tabak","year":"2011","journal-title":"J Neurosci"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508202102","article-title":"Revealing the Large-Scale Network Organization of Growth Hormone-Secreting Cells","volume":"102","author":"Bonnefont","year":"2005","journal-title":"Proc Natl Acad Sci USA"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.151339598","article-title":"Folliculostellate Cell Network: A Route for Long-Distance Communication in the Anterior Pituitary","volume":"98","author":"Fauquier","year":"2001","journal-title":"Proc Natl Acad Sci USA"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.17.10389","article-title":"Synchronized Spontaneous Ca Transients in Acute Anterior Pituitary Slices","volume":"273","author":"Gu\u00e9rineau","year":"1998","journal-title":"J Biol Chem"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceca.2011.11.007","article-title":"Coordination of Calcium Signals by Pituitary Endocrine Cells In Situ","volume":"51","author":"Hodson","year":"2012","journal-title":"Cell Calcium"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.2010.02052.x","article-title":"Investigating and Modelling Pituitary Endocrine Network Function","volume":"22","author":"Hodson","year":"2010","journal-title":"J Neuroendocrinol"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms1612","article-title":"Existence of Long-Lasting Experience-Dependent Plasticity in Endocrine Cell Networks","volume":"3","author":"Hodson","year":"2012","journal-title":"Nat Commun"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1007\/s10827-013-0470-8","article-title":"A Geometric Understanding of How Fast Activating Potassium Channels Promote Bursting in Pituitary Cells","volume":"36","author":"Vo","year":"2014","journal-title":"J Comput Neurosci"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.yfrne.2012.08.002","article-title":"Anterior Pituitary Cell Networks","volume":"33","author":"Le Tissier","year":"2012","journal-title":"Front Neuroendocrinol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.89.6.2471","article-title":"Rhythmogenic Effects of Weak Electrotonic Coupling in Neuronal Models","volume":"89","author":"Sherman","year":"1992","journal-title":"Proc Natl Acad Sci USA"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s11538-010-9559-7","article-title":"From Plateau to Pseudo-Plateau Bursting: Making the Transition","volume":"73","author":"Teka","year":"2011","journal-title":"Bull Math Biol"},{"key":"B19","doi-asserted-by":"crossref","DOI":"10.1093\/oso\/9780198805090.001.0001","volume-title":"Networks","author":"Newman","year":"2018"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8240(05)80292-7","article-title":"Anti-Phase, Asymmetric, and Aperiodic Oscillations in Electrically Active Cells I. Coupled Bursters","volume":"56","author":"Sherman","year":"1994","journal-title":"Bull Math Biol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00017.2006","article-title":"GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations","volume":"87","author":"Ben-Ari","year":"2007","journal-title":"Physiol Rev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1126\/science.1175509","article-title":"GABAergic Hub Neurons Orchestrate Synchrony in Developing Hippocampal Networks","volume":"326","author":"Bonifazi","year":"2009","journal-title":"Science"},{"key":"B23","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/BF00232524","article-title":"Single-Microelectrode Voltage Clamp Measurements of Pancreatic \u03b2-Cell Membrane Ionic Currents In Situ","volume":"143","author":"Rojas","year":"1995","journal-title":"J Membr Biol"},{"key":"B24","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1007\/BF00232525","article-title":"Estimating and Eliminating Junctional Current in Coupled Cell Populations by Leak Subtraction. A Computational Study","volume":"143","author":"Sherman","year":"1995","journal-title":"J Membrane Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1098\/rsta.2008.0110","article-title":"Cell Coupling in Mouse Pancreatic-Cells Measured in Intact Islets of Langerhans","volume":"366","author":"Zhang","year":"2008","journal-title":"Phi Trans R Soc A"},{"key":"B26","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.cmet.2016.06.020","article-title":"Beta Cell Hubs Dictate Pancreatic Islet Responses to Glucose","volume":"24","author":"Johnston","year":"2016","journal-title":"Cell Metab"},{"key":"B27","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1113\/jphysiol.1996.sp021361","article-title":"In Vivo Synchronous Membrane Potential Oscillations in Mouse Pancreatic-Cells: Lack of Co-Ordination Between Islets","volume":"493","author":"Valdeolmillos","year":"1996","journal-title":"J Physiol (Lond)"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-2725(03)00264-4","article-title":"The Effects of Connexin Phosphorylation on Gap Junctional Communication","volume":"36","author":"Lampe","year":"2004","journal-title":"J Biochem Cell Biol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1007\/s10827-016-0600-1","article-title":"From Global to Local: Exploring the Relationship Between Parameters and Behaviors in Models of Electrical Excitability","volume":"40","author":"Fletcher","year":"2016","journal-title":"J Comput Neurosci"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00948.2016","article-title":"Modeling the Diversity of Spontaneous and Agonist-Induced Electrical Activity in Anterior Pituitary Corticotrophs","volume":"117","author":"Fletcher","year":"2017","journal-title":"J Neurophysiol"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1007769","article-title":"Ion Channel Noise Shapes the Electrical Activity of Endocrine Cells","volume":"16","author":"Richards","year":"2020","journal-title":"PLos Comput Biol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.936160\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T17:11:08Z","timestamp":1657127468000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2022.936160\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,6]]},"references-count":31,"alternative-id":["10.3389\/fendo.2022.936160"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2022.936160","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,6]]},"article-number":"936160"}}