Department of Human Anatomy, Basic Medical College, Zunyi Medical University, Zunyi, 563006, China.
Department of Anatomy & K. K. Leung Brain Research Centre, Air Force Military Medical University, Xi'an, 710032, China.
Anat Sci Int. 2023 Sep;98(4):580-592. doi: 10.1007/s12565-023-00728-4. Epub 2023 May 9.
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.
中脑多巴胺能(DAergic)区域包括腹侧被盖区(VTA)和黑质致密部(SNc),参与多种脑功能。先前的研究表明,VTA/SNc 到伏隔核(NAc)的通路在奖励和动机中至关重要。此外,报道称,岛叶皮质(IC)内的 DAergic 神经支配在疼痛调节中发挥重要作用。为了研究 VTA/SNc 是否向 NAc 和 IC 发出侧支投射,我们向大鼠 NAc 注射逆行示踪剂荧光金(FG),向同侧 IC 注射荧光逆行示踪微球(RetroBeads)。然后,为了检测侧支投射神经元是否参与神经病理性疼痛,部分大鼠接受了备用神经损伤(SNI)手术。免疫荧光染色结果显示,FG、RetroBeads 和 FG/RetroBeads 双标记神经元在 VTA/SNc 双侧分布,以同侧为主。FG/RetroBeads 双标记神经元占 FG 和 RetroBeads 标记神经元总数的比例分别为 16.7%和 30.3%。约 90.3%的 FG/RetroBeads 双标记神经元显示多巴胺能神经元标志物酪氨酸羟化酶(TH)免疫反应性(IR),而只有 7.5%显示 GABA 能抑制性投射神经元标志物钙结合蛋白(PV)-IR 的一部分。SNI 后 1 周,约 53.1%和 33.6%的 FG 和 RetroBeads 标记神经元分别为 FG/Fos-和 RetroBeads/Fos-IR 神经元。最后,约 35.9%的 FG/RetroBeads 双标记神经元显示 Fos-IR。本研究表明,VTA/SNc 中的部分 DAergic 和 PV-IR GABA 能神经元向 NAc 和 IC 发出侧支投射,在 SNI 诱导的神经病理性疼痛下被激活,并可能有助于伤害感受的调节。