Multi-neuromeric origin of tyrosine hydroxylase-positive neurons within the substantia nigra and ventral tegmental area

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 th...

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Bibliographic Details
Authors: Ferrán Bertone, José Luis, Lucero-Arteaga, Franco, Ayad, Abdelmalik, Kutsenko Shchegolska, Yevheniy, Alonso Fuentes, Antonia, Ribeiro do Couto, Bruno, García-Cabezas, M.Á., Tseng, Kuei Y.
Format: article
Publication Date:2025
Country:España
Institution:Universidad de Murcia
Repository:DIGITUM. Depósito Digital Institucional de la Universidad de Murcia
OAI Identifier:oai:digitum.um.es:10201/186131
Online Access:https://doi.org/10.3389/fnana.2025.1612529
http://hdl.handle.net/10201/186131
Access Level:Open access
Keyword:No relacionado con ningún objetivo de desarrollo sostenible
Description
Summary: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.