Regulation of hippocampal synapse remodeling by epileptiform activity.
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.
Zha
Xiang-Ming
XM
Department of Biological Sciences, University of Iowa, Iowa City, IA 52242-1324, USA.
Green
Steven H
SH
Dailey
Michael E
ME
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
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