A NOVEL MECHANISM UNDERLYING ACTIVITY-INDUCED RAPID SYNAPTIC MATURATION†
Synapse development involves a series of very gradual structural, functional, and molecular changes. There is some uncertainty about the earliest initiating events that lead to synaptic contact. It seems that both the release machinery in presynaptic terminals and neurotransmitter receptor clusters in postsynaptic cells are being established in advance of the first connections. The presence of these precocious synaptic characteristics in both pre- and postsynaptic cells makes determining which partner is the initiator of synaptogenesis difficult.
Silent synapses are frequently found in the developing brain; in fact nascent synaptic networks have a high incidence of silent synapses. Maturation of presynaptic transmitter secretion machinery is a critical step in synaptogenesis. A new work, conducted in Shumin Duanís laboratory by Wanhua Shen et al., shows that a brief train of presynaptic action potentials rapidly awaken silent synapses by increasing the availability of synaptic vesicles for fusion through BDNF-triggered presynaptic actin remodelling mediated by the small GTPase Cdc42 (Activity-Induced Rapid Synaptic Maturation Mediated by Presynaptic Cdc42 Signaling. Neuron 50, 401-414, 2006).
Shenís team, using paired patch-clamp recordings from cultured hippocampal neurons at an early development stage, identified non functional contacts, different from the conventional silent synapses containing NMDA-only responses, for their lack of both AMPA- and NMDA-mediated synaptic responses. The authors show that pre-synaptic theta burst stimulation converts these contacts into functional synapses, via enhanced presynaptic glutamate release and actin polymerization induced by activation of BDNF-Cdc42 signaling at presynaptic release sites.
These findings reveal a novel mechanism underlying activity-induced rapid presynaptic maturation during a critical stage of synapse formation. †