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FASEB J ; 35(8): e21791, 2021 08.
Article in English | MEDLINE | ID: mdl-34320240

ABSTRACT

Chemical neurotransmission typically occurs through synapses. Previous ultrastructural examinations of monoamine neuron axon terminals often failed to identify a pre- and postsynaptic coupling, leading to the concept of "volume" transmission. Whether this results from intrinsic properties of these neurons remains undefined. We find that dopaminergic neurons in vitro establish a distinctive axonal arbor compared to glutamatergic or GABAergic neurons in both size and propensity of terminals to avoid direct contact with target neurons. While most dopaminergic varicosities are active and contain exocytosis proteins like synaptotagmin 1, only ~20% of these are synaptic. The active zone protein bassoon was found to be enriched in dopaminergic terminals that are in proximity to a target cell. Finally, we found that the proteins neurexin-1αSS4- and neuroligin-1A+B play a critical role in the formation of synapses by dopamine (DA) neurons. Our findings suggest that DA neurons are endowed with a distinctive developmental connectivity program.


Subject(s)
Axons/physiology , Calcium-Binding Proteins/metabolism , Cell Adhesion Molecules, Neuronal/metabolism , Corpus Striatum/cytology , Dopamine/metabolism , Dopaminergic Neurons/physiology , Neural Cell Adhesion Molecules/metabolism , Animals , Calcium-Binding Proteins/genetics , Cell Adhesion Molecules, Neuronal/genetics , Cell Differentiation , Coculture Techniques/methods , Dopamine/genetics , Gene Expression Regulation , Green Fluorescent Proteins , Immunohistochemistry , Mice, Transgenic , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Neural Cell Adhesion Molecules/genetics , Tyrosine 3-Monooxygenase/genetics , Tyrosine 3-Monooxygenase/metabolism
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