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 Duan’s 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).
Shen’s
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.