Subcellular and regional localization of mRNA translation in midbrain dopamine neurons

Midbrain dopaminergic (mDA) neurons exhibit extensive dendritic and axonal arborizations, but local protein synthesis is not characterized in these neurons. Here, we investigate messenger RNA (mRNA) localization and translation in mDA neuronal axons and dendrites, both of which release dopamine (DA). Using highly sensitive ribosome-bound RNA sequencing and imaging approaches, we find no evidence for mRNA translation in mDA axons. In contrast, mDA neuronal dendrites in the substantia nigra pars reticulata (SNr) contain ribosomes and mRNAs encoding the major components of DA synthesis, release, and reuptake machinery. Surprisingly, we also observe dendritic localization of mRNAs encoding synaptic vesicle-related proteins, including those involved in exocytic fusion. Our results are consistent with a role for local translation in the regulation of DA release from dendrites, but not from axons. Our translatome data define a molecular signature of sparse mDA neurons in the SNr, including the enrichment of Atp2a3/SERCA3, an atypical ER calcium pump.