Development/Plasticity/Repair Protracted Synaptogenesis after Activity-Dependent Spinogenesis in Hippocampal Neurons

Activity-dependent morphological plasticity of neurons is central to understanding how the synaptic network of the CNS becomes reconfigured in response to experience. In recent years, several studies have shown that synaptic activation that leads to the induction of long-term potentiation also drives the growth of new dendritic spines, raising the possibility that new synapses are made. We examine this directly by correlating time-lapse two-photon microscopy of newly formed spines on CA1 pyramidal neurons in organotypic hip-pocampal sliceswith electronmicroscopy. Our results show that, whereas spines that are only a fewhours old rarely form synapses, older spines, ranging from 15 to 19 h, consistently have ultrastructural hallmarks typical of synapses. This is in agreement with a recent in vivo study that showed that, after a few days, new spines consistently form functional synapses. In addition, our study provides amuchmore detailed understanding of the first fewhours after activity-dependent spinogenesis.Within tens ofminutes, physical contacts are formed with existing presynaptic boutons, which slowly, over the course of many hours, mature into new synapses. Key words: synaptic plasticity; two-photon imaging; correlated electron microscopy; theta-burst stimulation; LTP; spine