Combinatorial transcriptional regulation establishes subtype-appropriate synaptic properties in auditory neurons

Summary Neurons develop diverse synapses that vary in content, morphology, and size. Although transcriptional regulators of neurotransmitter identity have been identified, it remains unclear how other synaptic features are patterned among neuronal subtypes. In the auditory system, glutamatergic synaptic properties vary across three subtypes of spiral ganglion neurons (SGNs) that collectively encode sound information. Here, we show that a combinatorial Maf transcription factor code establishes SGN subtype identity and shapes both shared and subtype-appropriate synaptic properties. We find that c-Maf and Mafb have independent and opposing effects on synaptic morphology and auditory function, while also acting redundantly to impart subtype identities and drive synaptic differentiation needed for normal auditory responses. Additionally, c-Maf and Mafb are expressed at different levels across subtypes and regulate subtype-appropriate gene expression in a dose-dependent manner. Thus, functional diversity of Maf family members enables flexible and robust control of gene expression needed to generate synaptic heterogeneity across neuronal subtypes.