We examined the somatodendritic compartment of nigral dopaminergic neurons by immunocytochemistry and confocal microscopy, with the aim of identifying proteins that participate in dopamine packaging and release. Nigral dopaminergic neurons were identified by location, cellular features and tyrosine hydroxylase immunoreactivity. Immunoreactive puncta of vesicular monoamine transporter type 2 and proton ATPase, both involved in the packaging of dopamine for release, were located primarily in dopaminergic cell bodies, but were absent in distal dopaminergic dendrites. Many presynaptic proteins associated with transmitter release at fast synapses were absent in nigral dopaminergic neurons, including synaptotagmin 1, syntaxin1, synaptic vesicle proteins 2a and 2b, synaptophysin and synaptobrevin 1 (VAMP 1). On the other hand, syntaxin 3, synaptobrevin 2 (VAMP 2) and SNAP-25-immunoreactivities were found in dopaminergic somata and dendrites Our data imply that the storage and exocytosis of dopamine from the somatodendritic compartment of nigral dopaminergic neurons is mechanistically distinct from transmitter release at axon terminals utilizing amino acid neurotransmitters. Keywords dopamine; substantia nigra; somatodendritic; exocytosis; dopamine release proteins Parkinson's disease, a movement disorder involving the basal ganglia, results primarily from degeneration of the dopaminergic (DAergic) projection from substantia nigra (SN) to striatum (Birkmayer and Hornykiewicz, 1976). The underlying nigrostriatal pathway arises from large midbrain DAergic neurons situated in the SN pars compacta (SNc). Laterally extending dendrites emitted by the DAergic perikarya intermingle in the SNc and vertical dendrites extend ventrally into the adjacent pars reticulata (SNr) (Dahlström and Fuxe, 1964;Juraska et al., 1977;Wassef et al., 1981, Tepper et al., 1987. USA, pw20@nyu.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Author ManuscriptNeuroscience. Author manuscript; available in PMC 2010 December 1. Previous studies have shown that dopamine (DA) is released both by the nigrostriatal axonal terminals within striatum and by DAergic somata and dendrites in the midbrain (Björkland and Lindvall, 1975;Groves et al., 1975;Geffen et al., 1976;Nieoullon et al., 1977;Rice et al., 1994, Jaffe et al., 1998Chen and Rice, 2001 (Patel et al., 2009). Another important distinction is that DAergic terminals in striatum show typical presynaptic aggregates of agranular vesicles Nirenberg et al., 1997), whereas DAergic somata in SNc lack these aggregates , as do DAergic den...