A crucial phase in neuronal development is the integration of newborn neurons into circuits. The right balance must be struck between excitatory and inhibitory neurons; however, the mechanisms that control inhibitory neuron integration and drive the maturation of inhibitory connectivity remain largely uncharacterized. In this issue (p. 1807) Michael Francis and colleagues identify a novel, non-cell-autonomous mechanism that regulates inhibitory neuron synapse formation at the neuromuscular junction (NMJ). The authors examine the electrophysiology and structural organization of GABAergic synapses at the NMJ in a number of different C. elegans mutants with developmental or functional defects in excitatory motor neurons. These analyses reveal that the activity of excitatory cholinergic motor neurons, during a period that coincides with the development of postembryonic GABAergic motor neurons, critically affects the size and distribution of GABAergic pre- and post-synaptic specializations. Furthermore, a severe reduction of cholinergic inputs to newly born GABAergic neurons reduces their synaptic density but increases the synapse size. This study makes an important contribution to our understanding of how neuronal activity impacts synapse development and highlights the functional relationship between excitatory and inhibitory neurons during circuit formation.
