title: Adult neural progenitor cells reactivate superbursting in mature neural networks.
abstract: Behavioral recovery in animal models of human CNS syndromes suggests that transplanted stem cell derivatives can augment damaged neural networks but the mechanisms behind potentiated recovery remain elusive. Here we use microelectrode array (MEA) technology to document neural activity and network integration as rat primary neurons and rat hippocampal neural progenitor cells (NPCs) differentiate and mature. The natural transition from neuroblast to functional excitatory neuron consists of intermediate phases of differentiation characterized by coupled activity. High-frequency network-wide bursting or "superbursting" is a hallmark of early plasticity that is ultimately refined into mature stable neural network activity. Microelectrode array (MEA)-plated neurons transition through this stage of coupled superbursting before establishing mature neuronal phenotypes in vitro. When plated alone, adult rat hippocampal NPC-derived neurons fail to establish the synchronized bursting activity that neurons in primary and embryonic stem cell-derived cultures readily form. However, adult rat hippocampal NPCs evoke re-emergent superbursting in electrophysiologically mature rat primary neural cultures. Developmental superbursting is thought to accompany transient states of heightened plasticity both in culture preparations and across brain regions. Future work exploring whether NPCs can re-stimulate developmental states in injury models would be an interesting test of their regenerative potential.
authors.affiliation: J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Crystal L
authors.initials: CL
authors.lastname: Stephens
authors.forename: Hiroki
authors.initials: H
authors.lastname: Toda
authors.forename: Theo D
authors.initials: TD
authors.lastname: Palmer
authors.forename: Thomas B
authors.initials: TB
authors.lastname: DeMarse
authors.forename: Brandi K
authors.initials: BK
authors.lastname: Ormerod
mesh_terms: D000200:Action Potentials / Q000502:physiology; D053687:Adult Stem Cells / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004622:Embryo, Mammalian; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D019394:Ki-67 Antigen / Q000378:metabolism; D008839:Microelectrodes; D018613:Microscopy, Confocal; D019579:Neocortex / Q000166:cytology; D009415:Nerve Net / Q000502:physiology*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014162:Transfection; D050598:Vesicular Glutamate Transport Protein 1 / Q000378:metabolism; D050495:Vesicular Inhibitory Amino Acid Transport Proteins / Q000378:metabolism
chemical_list: D019394:Ki-67 Antigen; D009419:Nerve Tissue Proteins; D050598:Vesicular Glutamate Transport Protein 1; D050495:Vesicular Inhibitory Amino Acid Transport Proteins; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins