ORIGINAL RESEARCH ARTICLE

Front. Neuroanat., 19 May 2015 | http://dx.doi.org/10.3389/fnana.2015.00059

Long-range projection neurons of the mouse ventral tegmental area: a single-cell axon tracing analysis

Ana Aransay†,

Claudia Rodríguez-López†,

María García-Amado,

Francisco Clascá and

Lucía Prensa*

Departamento de Anatomía, Histología y Neurociencia, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

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.

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Keywords: dopamine, ventral pallidum, single-cell labeling, axonal branching, cortex, thalamus, parabraquial pigmented nucleus, rostral ventral tegmental area

Citation: Aransay A, Rodríguez-López C, García-Amado M, Clascá F and Prensa L (2015) Long-range projection neurons of the mouse ventral tegmental area: a single-cell axon tracing analysis. Front. Neuroanat. 9:59. doi: 10.3389/fnana.2015.00059

Received: 23 February 2015; Accepted: 24 April 2015;
Published: 19 May 2015.

Edited by:

Kathleen S. Rockland, Boston University School of Medicine, USA

Reviewed by:

Giorgio Innocenti, Karolinska Institutet, Sweden
Andre Parent, Université Laval, Canada

Copyright © 2015 Aransay, Rodríguez-López, García-Amado, Clascá and Prensa. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Lucía Prensa, Department of Anatomy, Histology and Neuroscience, Faculty of Medicine, Autonomous University of Madrid, Arzobispo Morcillo 4, 28029 Madrid, Spain, lucia.prensa@uam.es

†These authors have contributed equally to this work.