Protracted Synaptogenesis after Activity-Dependent Spinogenesis in Hippocampal Neurons

Max Planck Institute of Neurobiology, 82152 München-Martinsried, Germany.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.34). 08/2007; 27(30):8149-56. DOI: 10.1523/JNEUROSCI.0511-07.2007
Source: PubMed


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 hippocampal slices with electron microscopy. Our results show that, whereas spines that are only a few hours 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 a much more detailed understanding of the first few hours after activity-dependent spinogenesis. Within tens of minutes, physical contacts are formed with existing presynaptic boutons, which slowly, over the course of many hours, mature into new synapses.

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    • "(D) Several hours after synapse initiation, mature synaptic structures, such as a defined cluster of SVs and an identifiable synaptic cleft, can be observed. Plots summarize observations from (Nagerl and others 2007), in which live imaging was used to identify newly formed spines in hippocampal slices after theta burst stimulation and retrospective electron microscopy was used to score the presence of morphologically mature clusters of SVs and a synaptic cleft associated with new spines. (Left) Percentage of new spines that were associated with presynaptic boutons at the given times after spine formation. "
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    • "For example, cortical and thalamic afferents onto the same dendrite in the lateral nucleus of amygdala were distinguished by spine structure and function: thalamic inputs terminate on mushroom spines and show larger Ca 2+ transients than cortical inputs that make contacts on long spines (Humeau et al., 2005). Filopodial-like long spines have been proposed as learning spines because formation of filopodia is observed within minutes of LTP-inducing stimulation (Nagerl et al., 2007) "
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    • "As an underlying mechanism for off-line learning and memory formation LTP-like processes in M1 are discussed. LTP involves a cascade of processes over time, which can increase the efficacy of existing synapses and promote the formation of new synapses [46]. Accordingly, LTP-like processes are thought to continue after training, thus stabilizing the memory traces of the newly learned task. "
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