Differential regulation of medium spiny and cholinergic neurons in the nucleus accumbens core by the insular and medial prefrontal cortices in the rat
Differential regulation of medium spiny and cholinergic neurons in the nucleus accumbens core by the insular and medial prefrontal cortices in the rat
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DOI：
10.1007/s00424-021-02634-y
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发表时间：
2021-11-01
影响因子：
4.5
通讯作者：
Kobayashi, Masayuki
中科院分区：
文献类型：
--
作者：
Hirose, Kensuke;Nakaya, Yuka;Kobayashi, Masayuki
伏隔核(NAC)主要接受岛叶皮质(IC)和内侧前额叶皮质(MPFC)的皮质投射。在NAC神经元中，胆碱能中间神经元(CHNS)通过调节其放电和突触特性来调节中棘神经元(MSN)的活动，而MSN的比例与NAC神经元的95%相似。然而，对突触机制知之甚少，包括它们依赖于细胞类型的皮质伏隔投射特性和对NAC核心的胆碱能作用。在这里，我们对接受AAV5-hSyn-ChR2(H134R)-mCherry注射到IC或mPFC的大鼠的急性脑片标本进行了NAC MSN和CHNS的全细胞膜片钳记录。光刺激IC或mPFC轴突可在MSN诱发类似的锁相兴奋性突触后电流(EPSCs)。另一方面，光刺激mPFC轴突可诱发一致的EPSCs，而光刺激IC轴突可诱发小得多的EPSCs，这在CHNS中常常表现为失败。光诱发的EPSCs可被河豚毒素消除，并可被4-氨基吡啶恢复，提示皮质伏隔投射在MSN和CHNS中单频诱导EPSCs。卡巴胆碱能有效抑制光刺激IC或mPFC轴突引起的MSN和CHNS以及刺激mPFC轴突引起的CHNS中EPSCs的幅度。卡巴胆碱对EPSC的抑制作用可被阿托品或吡伦西平恢复，预先应用加拉胺、J104129、PD102807或AF-DX384不能阻断卡巴胆碱对EPSC的抑制作用。这些结果表明，NAC、MSN和CHNS受IC和mPFC的兴奋性投射的不同调节，这些皮层-累积区的兴奋性输入受到M-1受体激活的调节。
The nucleus accumbens (NAc) receives cortical projections principally from the insular cortex (IC) and medial prefrontal cortex (mPFC). Among NAc neurons, cholinergic interneurons (ChNs) regulate the activities of medium spiny neurons (MSNs), which make up similar to 95% of NAc neurons, by modulating their firing and synaptic properties. However, little is known about the synaptic mechanisms, including their cell-type-dependent corticoaccumbal projection properties and cholinergic effects on the NAc core. Here, we performed whole-cell patch-clamp recordings from NAc MSNs and ChNs in acute brain slice preparations obtained from rats that received an AAV5-hSyn-ChR2(H134R)-mCherry injection into the IC or mPFC. Light stimulation of IC or mPFC axons induced comparable phase-locked excitatory postsynaptic currents (EPSCs) in MSNs. On the other hand, ChNs showed consistent EPSCs evoked by light stimulation of mPFC axons, whereas light stimulation of IC axons evoked much smaller EPSCs, which often showed failure in ChNs. Light-evoked EPSCs were abolished by tetrodotoxin and were recovered by 4-aminopyridine, suggesting that corticoaccumbal projections monosynaptically induce EPSCs in MSNs and ChNs. Carbachol effectively suppressed the amplitude of EPSCs in MSNs and ChNs evoked by light stimulation of IC or mPFC axons and in ChNs evoked by stimulating mPFC axons. The carbachol-induced suppression was recovered by atropine or pirenzepine, while preapplication of gallamine, J104129, PD102807, or AF-DX384 did not block the carbachol-induced EPSC suppression. These results suggest that NAc MSNs and ChNs are differentially regulated by excitatory projections from the IC and mPFC and that these corticoaccumbal excitatory inputs are modulated by M-1 receptor activation.