title: Evolution of Network Synchronization during Early Epileptogenesis Parallels Synaptic Circuit Alterations.
abstract: In secondary epilepsy, a seizure-prone neural network evolves during the latent period between brain injury and the onset of spontaneous seizures. The nature of the evolution is largely unknown, and even its completeness at the onset of seizures has recently been challenged by measures of gradually decreasing intervals between subsequent seizures. Sequential calcium imaging of neuronal activity, in the pyramidal cell layer of mouse hippocampal in vitro preparations, during early post-traumatic epileptogenesis demonstrated rapid increases in the fraction of neurons that participate in interictal activity. This was followed by more gradual increases in the rate at which individual neurons join each developing seizure, the pairwise correlation of neuronal activities as a function of the distance separating the pair, and network-wide measures of functional connectivity. These data support the continued evolution of synaptic connectivity in epileptic networks beyond the latent period: early seizures occur when recurrent excitatory pathways are largely polysynaptic, while ongoing synaptic remodeling after the onset of epilepsy enhances intranetwork connectivity as well as the onset and spread of seizure activity.
authors.affiliation: Massachusetts General Hospital, Department of Neurology, Boston, Massachusetts 02114, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Kyle P
authors.identifier: http://orcid.org/0000-0003-0219-8113
authors.initials: KP
authors.lastname: Lillis
authors.affiliation: Massachusetts General Hospital, Department of Neurology, Boston, Massachusetts 02114, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Zemin
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Massachusetts General Hospital, Department of Neurology, Boston, Massachusetts 02114, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Michelle
authors.initials: M
authors.lastname: Mail
authors.affiliation: Stanford University, Department of Neurobiology, Stanford, California 94305, and.
authors.forename: Grace Q
authors.initials: GQ
authors.lastname: Zhao
authors.affiliation: Lehigh University, Department of Electrical and Computer Engineering, Bethlehem, Pennsylvania 18015.
authors.forename: Yevgeny
authors.initials: Y
authors.lastname: Berdichevsky
authors.affiliation: Massachusetts General Hospital, Department of Neurology, Boston, Massachusetts 02114, Harvard Medical School, Boston, Massachusetts 02115.
authors.forename: Brian
authors.initials: B
authors.lastname: Bacskai
authors.affiliation: Massachusetts General Hospital, Department of Neurology, Boston, Massachusetts 02114, Harvard Medical School, Boston, Massachusetts 02115, staley.kevin@mgh.harvard.edu.
authors.forename: Kevin J
authors.identifier: http://orcid.org/0000-0002-3072-518X
authors.initials: KJ
authors.lastname: Staley
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D006624:Hippocampus / Q000166:cytology*; D066298:In Vitro Techniques; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009415:Nerve Net / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010775:Photic Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013223:Statistics as Topic; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
chemical_list: D008164:Luminescent Proteins; D005680:gamma-Aminobutyric Acid; D002118:Calcium
keywords: calcium imaging; homeostasis; network; two-photon