Regulation of hippocampal synapse remodeling by epileptiform activity

• Published in: Molecular and cellular neuroscience Vol. 29; no. 4; pp. 494 - 506
• Main Authors: Zha, Xiang-ming, Green, Steven H., Dailey, Michael E.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2005
• Subjects: Animals; Animals, Newborn; Dendritic Spines - drug effects; Dendritic Spines - pathology; Dendritic Spines - physiology; Disks Large Homolog 4 Protein; Down-Regulation - drug effects; Down-Regulation - physiology; Epilepsy - chemically induced; Epilepsy - pathology; Epilepsy - physiopathology; GABA Antagonists - pharmacology; Guanylate Kinases; Hippocampus - drug effects; Hippocampus - pathology; Hippocampus - physiopathology; Intracellular Signaling Peptides and Proteins - metabolism; Membrane Proteins - metabolism; Neuronal Plasticity - drug effects; Neuronal Plasticity - physiology; Organ Culture Techniques; Pseudopodia - drug effects; Pseudopodia - pathology; Pseudopodia - physiology; Pyridazines - pharmacology; Rats; Sodium Channel Blockers - pharmacology; Synapses - drug effects; Synapses - pathology; Synapses - physiology; Synaptic Membranes - drug effects; Synaptic Membranes - metabolism; Synaptic Membranes - pathology; Synaptic Transmission - drug effects; Synaptic Transmission - physiology
• ISSN: 1044-7431; 1095-9327
• DOI: 10.1016/j.mcn.2005.04.007

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 ∼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.