JournalNeural Excitability, Synapses, and Glia

De novo synaptogenesis induced by GABA in the developing mouse cortex

Fig. 4 GABA release from SOM interneurons is sufficient and necessary for inhibitory and excitatory synaptogenesis during early development.(A) Experimental schematic and images of newly formed gephyrin cluster (green arrowhead) and spines (red arrowheads). (B) Summary data of photoactivation-induced de novo synaptogenesis (young, n = 23 dendrites, 13 cells; GABAzine, n = 22 dendrites, 13 cells; old at EP16 to EP18, n = 19 dendrites, 11 cells; spontaneous, n = 13 dendrites, 11 cells). (C) Axons of SOM and de novo gephyrin punctum (green arrowhead) and dendritic spine (red arrowhead) imaged at 1045 nm. (D) Proximity between an axon of SOM and a new gephyrin cluster (<2 μm: 28 of 33 new puncta, 17 cells) or spine (<2 μm: 35 of 39 new spines). (E) Experimental schematic and images of dendrites in noninfected and TeTxLC-infected slices at EP12. (F and G) Quantitative analysis of gephyrin puncta density at EP11 and EP12 (control, n = 13 cells; TeTxLC, n = 15 cells) and spine density at EP7 (control, n = 8 cells; TeTxLC, n = 10 cells). (H and I) Traces of mIPSCs (H) and mEPSCs (I) measured by whole-cell patch-clamp recordings. Quantitative analyses of mIPSCs (control, n = 11 cells; TeTxLC, n = 11 cells) and mEPSCs (control, n = 7 cells; TeTxLC, n = 11 cells) are shown.*P < 0.05, **P < 0.01; error bars represent SEM.

Dendrites of cortical pyramidal neurons contain intermingled excitatory and inhibitory synapses. We studied the local mechanisms that regulate the formation and distribution of synapses. We found that local γ-aminobutyric acid (GABA) release on dendrites of mouse cortical layer 2/3 pyramidal neurons could induce gephyrin puncta and dendritic spine formation via GABA type A receptor activation and voltage-gated calcium channels during early postnatal development. Furthermore, the newly formed inhibitory and excitatory synaptic structures rapidly gained functions. Bidirectional manipulation of GABA release from somatostatin-positive interneurons increased and decreased the number of gephyrin puncta and dendritic spines, respectively. These results highlight a noncanonical function of GABA as a local synaptogenic element shaping the early establishment of neuronal circuitry in mouse cortex.

Oh, W.C., Lutzu, S., Castillo, P.E., and Kwon, H.-B. (2016). De novo synaptogenesis induced by GABA in the developing mouse cortex. Science 353, 1037–1040.