NMDA receptor activation limits the number of synaptic connections during hippocampal development

Activity-dependent synaptic plasticity triggered by N-methyl-D-aspartate (N MDA) receptor activation is a fundamental property of many glutamatergic sy napses and may be critical for the shaping and refinement of the structural and functional properties of neuronal circuits during early postnatal deve lopment. Using a combined morphological and electrophysiological approach, we showed that chronic blockade of NMDA receptors in hippocampal slice cult ures during the first two weeks of postnatal development leads to a substan tial increase in synapse number and results in a more complex dendritic arb orization of CA1 pyramidal cells. Thus, the development of excitatory circu itry in the hippocampus is determined by two opposing processes: NMDA recep tor-independent synapse formation and NMDA receptor-dependent attenuation o f synaptogenesis.