Presynaptic GABA(B) Receptor Regulates Activity-Dependent Maturation and Patterning of Inhibitory Synapses through Dynamic Allocation of Synaptic Vesicles

Front Cell Neurosci. 2012 Dec 3;6:57. doi: 10.3389/fncel.2012.00057. eCollection 2012.


Accumulating evidence indicate that GABA regulates activity-dependent development of inhibitory synapses in the vertebrate brain, but the underlying mechanisms remain unclear. Here we combined live imaging of cortical GABAergic axons with single cell genetic manipulation to dissect the role of presynaptic GABA(B) receptors (GABA(B)Rs) in inhibitory synapse formation in mouse. Developing GABAergic axons form a significant number of transient boutons but only a subset was stabilized. Synaptic vesicles in these nascent boutons are often highly mobile in the course of tens of minutes. Activation of presynaptic GABA(B)Rs stabilized mobile vesicles in nascent boutons through the local enhancement of actin polymerization. Inactivation of GABA(B)Rs in developing basket interneurons resulted in aberrant pattern of bouton size distribution, reduced bouton density and reduced axon branching, as well as reduced frequency of miniature inhibitory currents in postsynaptic pyramidal neurons. These results suggest that GABA(B)Rs along developing inhibitory axons act as a local sensor of GABA release and promote presynaptic maturation through increased recruitment of mobile vesicle pools. Such release-dependent validation and maturation of nascent terminals is well suited to sculpt the pattern of synapse formation and distribution along axon branches.

Keywords: FRET; GABAB receptor; actin polymerization; activity-dependent development; inhibitory synapses; live cell imaging; synaptic vesicle dynamics.