Activity blockade increases the number of functional synapses in the hippocampus of newborn rats.
During development neuronal circuitries are refined by activity. Here we studied the role of spontaneous electrical activity in the regulation of synapse formation in the intact newborn (Postnatal Day 3; P3) rat hippocampus in vitro. The blockade of the spontaneous network activity with TTX led to an increase in the number of functional excitatory synapses in the CA3 area of the developing hippocampus. In parallel, there was a substantial increase in the expression levels of the presynaptic markers synaptophysin, synaptotagmin, and synapsin I and of GluR1 AMPA receptor subunits. These changes were associated with an increase in the frequency and amplitude of AMPA receptor-mediated miniature excitatory postsynaptic currents (mEPSCs). Our correlated immunocytochemical, electronmicroscopical, and electrophysiological experiments indicate that in the developing hippocampus spontaneous network activity controls the number of functional synapses.
Lauri
Sari E
SE
Department of Biosciences, Division of Animal Physiology, P.O. Box 65, University of Helsinki, 00014 Helsinki, Finland.
Lamsa
Karri
K
Pavlov
Ivan
I
Riekki
Ruusu
R
Johnson
Benjamin E
BE
Molnar
Elek
E
Rauvala
Heikki
H
Taira
Tomi
T
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002135:Calcium-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D007150:Immunohistochemistry; D008562:Membrane Glycoproteins / Q000378:metabolism; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009434:Neural Pathways / Q000254:growth & development* / Q000378:metabolism* / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D026941:Sodium Channel Blockers / Q000494:pharmacology; D016704:Synapsins / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism; D050857:Synaptotagmins; D013779:Tetrodotoxin / Q000494:pharmacology
D002135:Calcium-Binding Proteins; D018691:Excitatory Amino Acid Antagonists; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D018091:Receptors, AMPA; D026941:Sodium Channel Blockers; D016704:Synapsins; D016708:Synaptophysin; D050857:Synaptotagmins; D013779:Tetrodotoxin