Redefining dopaminergic synapses beyond the classical paradigm

Synapses are traditionally defined by the presence of presynaptic vesicle pools and postsynaptic densities. Dopaminergic neurons, however, frequently form bouton-like structures that lack these conventional postsynaptic specializations. Recently, high-resolution imaging techniques such as electron microscopy and correlative light and electron microscopy, along with nanosensors and in vitro models, have revealed the molecular identities and spatial organization of distinct vesicle pools in dopaminergic terminals. In this review, we discuss how recent findings have reshaped current understanding of dopamine vesicles, revealing a structural continuum that includes non-classical architectures. We highlight emerging concepts such as dopamine hub synapses and vesicle heterogeneity in dopaminergic terminals. Finally, we examine how dysfunction in Parkinson's disease-associated proteins affects synaptic integrity and predisposes dopaminergic neurons to selective vulnerability.