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Collateral projections from the ventral tegmental area/substantia nigra pars compacta to the nucleus accumbens and insular cortex in the rat

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Abstract

Midbrain dopaminergic (DAergic) regions including ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) are involved in diverse brain functions. Previous studies demonstrated that the VTA/SNc to nucleus accumbens (NAc) pathway is critical in reward and motivation. Moreover, DAergic innervations within the insular cortex (IC) are reported to play important roles in pain regulation. To investigate whether VTA/SNc sends collateral projections to NAc and IC, we injected retrograde tracer Fluoro-Gold (FG) into the NAc and Fluorescent retrograde tracer beads (RetroBeads) into the ipsilateral IC in rats. Then, to detect whether collateral projection neurons participate in neuropathic pain, parts of the rats received the spare nerve injury (SNI) surgery. The immunofluorescence staining results showed that FG, RetroBeads, and FG/RetroBeads double-labeled neurons were distributed in the VTA/SNc bilaterally with an ipsilateral predominance. The proportion of FG/RetroBeads double-labeled neurons to the total number of FG and RetroBeads-labeled neurons was 16.7% and 30.3%, respectively. About 90.3% of FG/RetroBeads double-labeled neurons showed DAergic neuron marker tyrosine hydroxylase (TH)-immunoreactive (IR), whereas, only 7.5% exhibited a subset of GABAergic inhibitory projection neuron marker parvalbumin (PV)-IR. One week after SNI, about 53.1% and 33.6% of FG- and RetroBeads-labeled neurons were FG/Fos- and RetroBeads/Fos-IR neurons, respectively. Finally, about 35.9% of the FG/RetroBeads double-labeled neurons showed Fos-IR. The present study indicates that parts of DAergic and PV-IR GABAergic neurons in the VTA/SNc send collateral projections to both NAc and IC, which are activated under SNI-induced neuropathic pain, and probably contribute to the regulation of nociception.

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Data availability

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (No. 81701115, 82130034), Innovation Capability Support Program of Shaanxi Province (No. 2021TD-57), and Natural Science Foundation of Sichuan Province (No. 2023NSFSC1566).

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Authors and Affiliations

  1. Department of Human Anatomy, Basic Medical College, Zunyi Medical University, Zunyi, 563006, China

    Cheng-Bo He, Yuan Jin, Yan Li & Qian Zhang

  2. Department of Anatomy & K. K. Leung Brain Research Centre, Air Force Military Medical University, Xi’an, 710032, China

    Cheng-Bo He, Bai Yang, Yu-Lin Dong & Yun-Qing Li

  3. Department of Anatomy, Basic Medical College, Dali University, Dali, 671000, China

    Mang Xu & Yun-Qing Li

  4. Key Laboratory of Brain Science Research and Transformation in Tropical Environment of Hainan Province, Haikou, 571199, China

    Juan Yang, Xi-Nan Yi & Yun-Qing Li

  5. Department of Cardiothoracic Surgery, General Hospital of Western Theater Command, Chengdu, 610083, China

    Jian Wang

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Contributions

YQL, JW, and YLD designed the study; JW and CBH wrote the manuscript; CBH, JY, YL, YB, MX, and JY conducted the experiments; CBH, JY, YL, YB and MX complete the data analysis; YQL, YLD, QZ and XNY provided language modification and edited the manuscript. All authors read and approved the final manuscript.

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Correspondence to Jian Wang or Yun-Qing Li.

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He, CB., Jin, Y., Li, Y. et al. Collateral projections from the ventral tegmental area/substantia nigra pars compacta to the nucleus accumbens and insular cortex in the rat. Anat Sci Int 98, 580–592 (2023). https://doi.org/10.1007/s12565-023-00728-4

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