GABAA receptors (γ-aminobutyric acid-gated receptors type A) are the essential structural and functional postsynaptic components of inhibitory synapses in the mammalian brain. They belong to a family of GABA-gated Cl/HCO3-permeable ion channels which are built as hetero-pentamers of subunits classified as α(1-6), β(1-3), γ(1-3), δ, ε, π, θ and ρ(1-3). How, where, and when the inhibitory synapses are formed is tightly regulated during early brain development and later synaptogenesis by genetic and environmental factors. Multiple proteins have been shown to participate in the initiation and functional maturation of inhibitory synapses, including the postsynaptic adhesion protein neuroligin 2 (NL-2). This study examined how GABAA receptors and NL2 interact to initiate the formation of synapses using a co-culture model of embryonic rat GABAergic neurons and HEK293 cells expressing synaptic α2β2γ2 or extrasynaptic α4β3δ GABAA receptors together with NL-2. We present evidence for a synergistic interaction between GABAA receptors and NL-2 based on structural and functional analysis of synapses, with the α2β2γ2 receptors showing a significantly greater effect in facilitating the NL-2-dependent induction and functional maturation of synapses than α4β3δ receptors. In biochemical assays, the interaction between the α2β2γ2 receptors and NL-2 was detected and shown to be mediated by the large intracellular loop of the γ2 subunit. Our findings contribute to increasing experimental evidence indicating that multiple protein-protein interactions contribute incrementally and cooperatively to the initiation and functional development of inhibitory synapses and point to an important role of GABAA receptors in these processes.