ORIGINAL RESEARCH article

Front. Neuroanat.

Volume 19 - 2025 | doi: 10.3389/fnana.2025.1612529

This article is part of the Research TopicDopaminoceptive Forebrain Regions: A Search for Structural and Functional Organization Underlying Normal and Impaired Social AdaptationView all 5 articles

Multi-Neuromeric developmental origin of Tyrosine Hydroxylase-positive neurons within the Substantia Nigra and Ventral Tegmental Area

Provisionally accepted
José L FerranJosé L Ferran1,2*Franco Lucero-ArteagaFranco Lucero-Arteaga3,4Abdelmalik AyadAbdelmalik Ayad1,2Yevheniy KutsenkoYevheniy Kutsenko1,2A AlonsoA Alonso1,2B Ribeiro Do CoutoB Ribeiro Do Couto2,5M Á García-CabezasM Á García-Cabezas6Kuei Y TsengKuei Y Tseng7*
  • 1Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, Murcia, Spain
  • 2Biomedical Research Institute of Murcia (IMIB), Palmar, Murcia, Spain
  • 3National Scientific and Technical Research Council (CONICET), Buenos Aires, Buenos Aires, Argentina
  • 4Centro de producción de Animales de Experimentación, Facultad de Ciencias Veterinarias. Universidad Nacional de La Pampa, Argentina., General Pico, Argentina
  • 5Department of Human Anatomy and Psychobiology. Faculty of Psychology. University of Murcia, Murcia, Murcia, Spain
  • 6Department of Anatomy, Histology and Neuroscience, Faculty of Medicine, Autonomous University of Madrid, Madrid, Madrid, Spain
  • 7Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States

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During early developmental stages, the brain is divided into three primary regions: the forebrain (prosencephalon), the hindbrain (rhombencephalon), and the spinal cord. These regions are further segmented into transverse units called neuromeres, each with distinct molecular identities that guide their specialization through development. Such modular organization is evolutionarily conserved and shapes the structural and functional complexity of the brain. The substantia nigra (SN) and ventral tegmental area (VTA) are key midbrain regions involved in reward, motivation, and motor control. They contain dopamine-producing tyrosine hydroxylase (TH)-positive neurons, which are historically classified into three anatomical groups—A8 (retrorubral field), A9 (SN pars compacta), and A10 (VTA)—each with distinct anatomical and functional properties. Recent studies revealed further sub-regional organization along medial-lateral and anterior-posterior gradients, suggesting specialized roles tied to their developmental origins. This study uses the prosomeric framework to map the segmental distribution of TH-positive neurons within the SN and VTA across different mammalian species and developmental stages. Using a comparative analysis of rodent, non-human primate and human specimens, we were able to demonstrate that TH-positive neurons within the SN and VTA exhibit a multi-neuromeric organization, with neuronal populations distributed across the diencephalic prosomeres (dp1-dp3), the midbrain prosomeres (mp1-mp2) and the isthmic rhombomere (r0). It is therefore conceivable that such multi-neuromeric origin of TH-positive neurons within the SN and VTA likely influence the patterns of connectivity and functional specialization of the dopamine system.

Keywords: Diencephalon, prosomeres, mesomeres, Sn, VTA, rhombomere, Dopamine, Nigrostriatal. (Min.5-Max. 8)

Received: 15 Apr 2025; Accepted: 09 May 2025.

Copyright: © 2025 Ferran, Lucero-Arteaga, Ayad, Kutsenko, Alonso, Ribeiro Do Couto, García-Cabezas and Tseng. 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:
José L Ferran, Department of Human Anatomy and Psychobiology, Faculty of Medicine, University of Murcia, Murcia, 30003, Murcia, Spain
Kuei Y Tseng, Department of Anatomy and Cell Biology, College of Medicine, University of Illinois at Chicago, Chicago, 60612-7308, Illinois, United States

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Supplementary Material