Abstract
Pathways arising from the ventral tegmental area (VTA) release dopamine and other neurotransmitters during the expectation and achievement of reward, and are regarded as central links of the brain networks that create drive, pleasure, and addiction. While the global pattern of VTA projections is well-known, the actual axonal wiring of individual VTA neurons had never been investigated. Here, we labeled and analyzed the axons of 30 VTA single neurons by means of single-cell transfection with the Sindbis-pal-eGFP vector in mice. These observations were complemented with those obtained by labeling the axons of small populations of VTA cells with iontophoretic microdeposits of biotinylated dextran amine. In the single-cell labeling experiments, each entire axonal tree was reconstructed from serial sections, the length of terminal axonal arbors was estimated by stereology, and the dopaminergic phenotype was tested by double-labeling for tyrosine hydroxylase immunofluorescence. We observed two main, markedly different VTA cell morphologies: neurons with a single main axon targeting only forebrain structures (FPN cells), and neurons with multibranched axons targeting both the forebrain and the brainstem (F + BSPN cells). Dopaminergic phenotype was observed in FPN cells. Moreover, four “subtypes” could be distinguished among the FPN cells based on their projection targets: (1) “Mesocorticolimbic” FPN projecting to both neocortex and basal forebrain; (2) “Mesocortical” FPN innervating the neocortex almost exclusively; (3) “Mesolimbic” FPN projecting to the basal forebrain, accumbens and caudateputamen; and (4) “Mesostriatal” FPN targeting only the caudateputamen. While the F + BSPN cells were scattered within VTA, the mesolimbic neurons were abundant in the paranigral nucleus. The observed diversity in wiring architectures is consistent with the notion that different VTA cell subpopulations modulate the activity of specific sets of prosencephalic and brainstem structures.
Highlights
The ventral tegmental area (VTA) subdivisions parabrachial pigmented nucleus (PBP), PN, and rostral ventral tegmental area (rVTA) were outlined in sagittal sections of one mouse mesencephalon stained for tyrosine hydroxylase (TH), which identifies solely DAergic neurons in these regions (Fu et al, 2012), based on the atlas of Franklin and Paxinos (2007) and the delineation proposed by Ikemoto (2007)
A similar scarceness of TH+ neurons occurs at the posterior aspect of VTA, which corresponds to the ventral tegmental tail (VTT) subdivision delimited by Ikemoto (2007), posterior to PN, slightly ventral to the caudal pole of PBP and above the interpeduncular nucleus (IP) (Figure 1B)
The number and combinations of target structures innervated by single DAergic and nonDAergic VTA neurons had not been examined to date, and the existence of neurons with such diverse and specific anatomical axonal arborizations that might funnel information simultaneously to multiple cortical and subcortical structures, such as the mesocorticolimbic neurons described here, had been unsuspected until now
Summary
Pitchers et al, 2014; Ranaldi, 2014), and in the physiopathology of psychiatric disorders like schizophrenia (Sesack and Carr, 2002; Laviolette, 2007; Lau et al, 2013) or major depression (Nestler and Carlezon, 2006; Friedman et al, 2009; Russo and Nestler, 2013) This ventral mesencephalic territory has been subdivided in up to eight subdivisions/nuclei whose delineation and terminology varies substantially between authors (Swanson, 1982; Ikemoto, 2007; Fu et al, 2012): parabrachial pigmented nucleus (PBP); paranigral (PN); parainterfascicular (PIF); rostral ventral tegmental area (rVTA); ventral tegmental tail (VTT); interfascicular (IF); rostral linear (RLi); and caudal linear (CLi). DAergic axons were seen to release GABA using the vesicular monoamine transporter VMAT2 activity, instead of the already-known vesicular GABA transporter VGAT (Tritsch et al, 2012)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have