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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Animals, Newborn
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Dendritic Spines / drug effects
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Dendritic Spines / pathology
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Dendritic Spines / physiology*
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Disks Large Homolog 4 Protein
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Down-Regulation / drug effects
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Down-Regulation / physiology
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Epilepsy / chemically induced
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Epilepsy / pathology
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Epilepsy / physiopathology*
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GABA Antagonists / pharmacology
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Guanylate Kinases
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Hippocampus / drug effects
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Hippocampus / pathology
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Hippocampus / physiopathology*
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Intracellular Signaling Peptides and Proteins / metabolism
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Membrane Proteins / metabolism
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Neuronal Plasticity / drug effects
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Neuronal Plasticity / physiology*
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Organ Culture Techniques
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Pseudopodia / drug effects
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Pseudopodia / pathology
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Pseudopodia / physiology
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Pyridazines / pharmacology
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Rats
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Sodium Channel Blockers / pharmacology
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Synapses / drug effects
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Synapses / pathology
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Synapses / physiology*
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Synaptic Membranes / drug effects
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Synaptic Membranes / metabolism
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Synaptic Membranes / pathology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Disks Large Homolog 4 Protein
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Dlg4 protein, mouse
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GABA Antagonists
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Intracellular Signaling Peptides and Proteins
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Membrane Proteins
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Pyridazines
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Sodium Channel Blockers
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gabazine
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Guanylate Kinases