title: Regulation of hippocampal synapse remodeling by epileptiform activity.
abstract: We examined the regulation of dendritic spines and synapses by epileptiform activity (EA) in rat hippocampal slice cultures. EA, which was induced by a GABA(A) receptor inhibitor, gabazine, reduced pyramidal neuron spine density by approximately 50% after 48 h and also caused an increase in the average length of remaining spines. To directly determine the effects of EA on synapses, we used fluorescent protein-tagged PSD95, which marks postsynaptic densities. EA induced a net loss of synapses on spines but not shafts; conversely, activity blockade (TTX) induced a loss of shaft synapses. Time-lapse confocal imaging in live tissue slices revealed that EA (1) shifts the balance of synapse gain and loss in dendrites leading to a net loss of spine synapses and (2) induces the formation of new filopodia-like dendritic structures having abnormally slow motility. These results identify EA-induced changes in the density and distribution of synaptic structures on dendrites.
authors.affiliation: Department of Biological Sciences, University of Iowa, Iowa City, IA 52242-1324, USA.
authors.forename: Xiang-Ming
authors.initials: XM
authors.lastname: Zha
authors.forename: Steven H
authors.initials: SH
authors.lastname: Green
authors.forename: Michael E
authors.initials: ME
authors.lastname: Dailey
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology*; D018756:GABA Antagonists / Q000494:pharmacology; D051528:Guanylate Kinases; D006624:Hippocampus / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D011554:Pseudopodia / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013569:Synapses / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D018756:GABA Antagonists; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D011724:Pyridazines; D026941:Sodium Channel Blockers; C049853:gabazine; D051528:Guanylate Kinases