NMDA receptor activation limits the number of synaptic connections during hippocampal development.
Activity-dependent synaptic plasticity triggered by N-methyl-d-aspartate (NMDA) receptor activation is a fundamental property of many glutamatergic synapses and may be critical for the shaping and refinement of the structural and functional properties of neuronal circuits during early postnatal development. Using a combined morphological and electrophysiological approach, we showed that chronic blockade of NMDA receptors in hippocampal slice cultures during the first two weeks of postnatal development leads to a substantial increase in synapse number and results in a more complex dendritic arborization of CA1 pyramidal cells. Thus, the development of excitatory circuitry in the hippocampus is determined by two opposing processes: NMDA receptor-independent synapse formation and NMDA receptor-dependent attenuation of synaptogenesis.
Lüthi
A
A
Brain Research Institute, University of Zurich, Winterthurerstrasse 190, CH-8057, Zurich, Switzerland.
Schwyzer
L
L
Mateos
J M
JM
Gähwiler
B H
BH
McKinney
R A
RA
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D022081:Cell Surface Extensions; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development*; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors; D008239:Lysine / Q000031:analogs & derivatives*; D018613:Microscopy, Confocal; D018408:Patch-Clamp Techniques; D010879:Piperazines / Q000494:pharmacology; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; D007473:Ion Channels; D010879:Piperazines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C013411:biocytin; D008239:Lysine