Neuroligins, β-neurexin, and PSD-95 modulate excitatory and inhibitory synapse formation. An example of the effects of a member of the neuroligin (NLG) family, NLG2 (green), on synapse formation. (A) Expression of NLG2 in hippocampal neurons increases the number of excitatory (VGLUT-positive; red) and inhibitory (VGAT-positive; blue) presynaptic contacts. (B) Interfering with β-neurexin and NLG2 coupling blocks NLG2 (green)-mediated effects on inhibitory synapse formation. Treatment with a soluble form of β-neurexin decreases the number of sites positive for VGAT (blue). (C) NLG2 (red) is normally localized at inhibitory synaptic contacts (VGAT-positive; blue; upper panel). Overexpression of PSD-95 shifts NLG2 from inhibitory to excitatory (PSD-95-positive; green) synapses (colocalization of NLG2 and PSD-95 appears in orange; lower panel).