Inhibitory synaptic transmissions to the bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area are enhanced in rats exposed to chronic mild stress.
Inhibitory synaptic transmissions to the bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area are enhanced in rats exposed to chronic mild stress.
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DOI：
10.1186/s13041-020-00684-4
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发表时间：
2020-10-15
期刊：
影响因子：
3.6
通讯作者：
Minami M
中科院分区：
文献类型：
--
作者：
Hara R;Takahashi D;Takehara T;Amano T;Minami M
抑郁症和慢性疼痛的共病早已在临床上得到认识，一些临床前研究已经证明慢性疼痛动物模型具有抑郁样行为。这些发现表明抑郁症和慢性疼痛存在共同的神经元基础。最近，我们报道了中脑边缘多巴胺能系统在慢性疼痛期间通过增强对从终纹背外侧床核（dlBNST）投射到腹侧被盖区（VTA）的神经元的抑制性突触输入而受到强直性抑制，这表明这种神经塑性变化对中脑边缘多巴胺能系统的强直性抑制可能与慢性疼痛诱发的抑郁样行为有关。在这项研究中，我们假设在抑郁症动物模型中，VTA 投射 dlBNST 神经元的抑制性突触输入也会增强，从而抑制中脑边缘多巴胺能系统。为了验证这一假设，我们使用从暴露于慢性轻度应激（CMS）的大鼠（一种广泛使用的抑郁症动物模型）中制备的脑切片进行了全细胞膜片钳电生理学分析。结果显示，与无应激组相比，CMS 组中 VTA 投射的 dlBNST 神经元自发抑制性突触后电流的频率显着增强。研究结果显示，在抑郁症大鼠模型中，VTA 投射的 dlBNST 神经元的抑制性突触输入增强，表明这种神经塑性变化是抑郁症和慢性疼痛常见的神经元机制，导致中脑边缘多巴胺能系统功能障碍，从而诱发抑郁样行为。
The comorbidities of depression and chronic pain have long been recognized in the clinic, and several preclinical studies have demonstrated depression-like behaviors in animal models of chronic pain. These findings suggest a common neuronal basis for depression and chronic pain. Recently, we reported that the mesolimbic dopaminergic system was tonically suppressed during chronic pain by enhanced inhibitory synaptic inputs to neurons projecting from the dorsolateral bed nucleus of the stria terminalis (dlBNST) to the ventral tegmental area (VTA), suggesting that tonic suppression of the mesolimbic dopaminergic system by this neuroplastic change may be involved in chronic pain-induced depression-like behaviors. In this study, we hypothesized that inhibitory synaptic inputs to VTA-projecting dlBNST neurons are also enhanced in animal models of depression, thereby suppressing the mesolimbic dopaminergic system. To test this hypothesis, we performed whole-cell patch-clamp electrophysiology using brain slices prepared from rats exposed to chronic mild stress (CMS), a widely used animal model of depression. The results showed a significant enhancement in the frequency of spontaneous inhibitory postsynaptic currents in VTA-projecting dlBNST neurons in the CMS group compared with the no stress group. The findings revealed enhanced inhibitory synaptic inputs to VTA-projecting dlBNST neurons in this rat model of depression, suggesting that this neuroplastic change is a neuronal mechanism common to depression and chronic pain that causes dysfunction of the mesolimbic dopaminergic system, thereby inducing depression-like behaviors.
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影响因子：
5.3
作者：
Takahashi, Daiki;Asaoka, Yuta;Minami, Masabumi
通讯作者：
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影响因子：
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Kash, Thomas L.
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影响因子：
6.8
作者：
Bessa JM;Morais M;Marques F;Pinto L;Palha JA;Almeida OF;Sousa N
通讯作者：
Sousa N
影响因子：
3.4
作者：
Yamauchi, Naoki;Takahashi, Daiki;Minami, Masabumi
通讯作者：
Minami, Masabumi