Single Nigrostriatal Dopaminergic Neurons Form Widely Spread and Highly Dense Axonal Arborizations in the Neostriatum

Abstract

The axonal arbors of single nigrostriatal dopaminergic neurons were visualized with a viral vector expressing membrane-targeted green fluorescent protein in rat brain. All eight reconstructed tyrosine hydroxylase-positive dopaminergic neurons possessed widely spread and highly dense axonal arborizations in the neostriatum. All of them emitted very little axon collateral arborization outside of the striatum except for tiny arborization in the external pallidum. The striatal axonal bush of each reconstructed dopaminergic neuron covered 0.45-5.7% (mean Ϯ SD ϭ 2.7 Ϯ 1.5%) of the total volume of the neostriatum. Furthermore, all the dopaminergic neurons innervated both striosome and matrix compartments of the neostriatum, although each neuron's arborization tended to favor one of these compartments. Our findings demonstrate that individual dopaminergic neurons of the substantia nigra can broadcast a dopamine signal and exert strong influence over a large number of striatal neurons. This divergent signaling should be a key to the function of the nigrostriatal system in dopamine-based learning and suggests that neurodegeneration of individual nigral neurons can affect multiple neurons in the striatum. Thus, these results would also contribute to understanding the clinicopathology of Parkinson's disease and related syndromes.

Striosome–dendron bouquets highlight a unique striatonigral circuit targeting dopamine-containing neurons

“…Alternatively, the neuropil density from infected neurons might be higher in the striosomes than in the surrounding matrix. It is reported that individual dopamine-containing neurons that lie ventrally or along the SNc/SNr border, which given our findings likely include neurons that form the dendrons of the striosome-dendron bouquets, target both striatal compartments, with a notable preference for striosomes (48)(49)(50).…”

Somatodendritic dopamine release: recent mechanistic insights

“…The axons of DA neurons emerge from a proximal dendrite and project to the striatal complex in a roughly topographical manner [85][86][87][88]. All DA neurons innervate both the striosome (also called patch) and matrix compartments of the striatum, although the axonal arborization of dorsal tier neurons favour the matrix, whereas ventral tier neurons tend to favour striosomes [10,86,89,90]. Within these populations, additional biochemical and physiological differences confer differential excitability, as well as differential vulnerability to pathophysiological insults [88,91 -94], with greater susceptibility of ventral tier neurons of the SNc to degeneration in PD (and animal models of the disease) than those in the dorsal tier of SNc or the VTA [95,96].…”

“…Forebrain DA innervation originates in midbrain DA neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) [9]. Axons from these DA neurons provide rich innervation of the distant striatal complex [10]: the nigrostriatal DA pathway projects from SNc preferentially to dorsal striatum (caudate-putamen, CPu), and the mesolimbic DA pathway projects from VTA preferentially to ventral striatum (nucleus accumbens, NAc) and to prefrontal cortex [11,12].…”

Cytoprotective effects of growth factors: BDNF more potent than GDNF in an organotypic culture model of Parkinson's disease

“…A9 neurons have a distinctive cellular morphology, with long, thin axons that are poorly myelinated and massively arborized (100,(125)(126)(127). This morphology has been demonstrated to increase metabolic demands and the risk of oxidative stress in A9 cells compared to other dopaminergic cell populations (128)(129)(130).…”

“…These findings indicate that AQP4 plays a crucial role in the SN under normal physiological conditions, which can be attributed to several factors. First, the morphology of the dopaminergic neurons in the SNpc as well as their pacemaker activity make these neurons particularly metabolically active (38,100,(125)(126)(127)(128)(129)(130)(131)(132)(133)(134), with higher oxygen consumption rates and elevated mitochondrial energetic metabolism than dopaminergic neurons in the VTA as well as in the olfactory bulb in primary cultures (130). The elevated energetic requirements produce large amounts of metabolic water, as each glucose molecule generate 42 water molecules from glycolysis to oxidative phosphorylation (441).…”