A balanced network of excitatory and inhibitory synapses is required for correct brain function, and any perturbations to this balance can give rise to neurological and psychiatric disorders. It has been shown previously that FGF22 and FGF7 promote excitatory or inhibitory synapse formation, respectively, in the hippocampus, but how do these ligands mediate their synaptogenic effects? Here, Hisashi Umemori and co-workers use various FGF receptor knockout mice to address this question (p. ). They first show that excitatory presynaptic differentiation is impaired in Fgfr2b and Fgfr1b mutant mice. Following on from this, they reveal that both FGFR2b and FGFR1b act downstream of FGF22 and are required for FGF22-dependent excitatory presynaptic differentiation. The authors further show that the kinase activity of FGFR2b as well as its ability to bind to FRS2 and PI3K is required for it to respond to FGF22. By contrast, they report, inhibitory presynaptic differentiation is defective only in Fgfr2b, and not Fgfr1b, mutants. In line with this, they demonstrate that FGF7 requires FGFR2b and not FGFR1b to mediate its effect on inhibitory presynaptic differentiation. Together, these findings indicate that distinct but overlapping sets of FGF receptors sculpt excitatory and inhibitory synapse formation in the mammalian brain.
