Astrocytic L-Lactate Signaling Facilitates Amygdala-Anterior Cingulate Cortex Synchrony and Decision Making in Rats
Astrocytic L-Lactate Signaling Facilitates Amygdala-Anterior Cingulate Cortex Synchrony and Decision Making in Rats
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星形胶质细胞 L-乳酸信号传导促进大鼠杏仁核-前扣带皮层同步和决策
DOI：
10.1016/j.celrep.2017.11.012
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发表时间：
2017-11-28
期刊：
影响因子：
8.8
通讯作者：
Li, Ying
中科院分区：
文献类型：
--
作者：
Wang, Jun;Tu, Jie;Li, Ying
人脑成像研究表明，前扣带皮层（ACC）是介导内脏-疼痛-认知相互作用的关键脑区。最近，我们的特点是损害的长时程增强和尖峰场的一致性在基底外侧杏仁核（BLA）-ACC网络与决策缺陷与内脏高敏感性（VH）大鼠。现在，通过结合综合神经生物学方法，我们表明，ACC反应性星形胶质细胞增生和乳酸释放的活动依赖性损害发生在VH大鼠。外源性乳酸供应可以挽救慢性内脏痛引起的ACC相位锁定和决策功能障碍，这可以通过ACC星形胶质细胞的光遗传学激活来模拟。在决策任务期间自由移动动物的大规模电生理记录表明，光遗传星形胶质细胞激活提高了决策性能，并参与了ACC相位锁定和BLA-ACC信息流。总的来说，这些观察结果支持“星形胶质细胞-神经元L-乳酸穿梭”的想法，并表明靶向星形胶质细胞可能有助于慢性内脏痛下的认知功能障碍。
Human brain imaging studies have revealed the anterior cingulate cortex (ACC) as a key brain region for mediating visceral-pain-cognitive interactions. Recently, we characterized impairments of long-term potentiation and spike-field coherence in the basolateral amygdala (BLA)-ACC network in association with a decision-making deficit in rats with visceral hypersensitivity (VH). Now, by combining integrative neurobiological approaches, we show that ACC-reactive astrogliosis and activity-dependent impairment of lactate release occur in VH rats. Exogenous lactate supply rescues chronic-visceralpain-caused impairments of ACC phase locking and decision making, which can be mimicked by optogenetic activation of ACC astrocytes. Large-scale electrophysiological recordings in free-moving animals during a decision-making task indicate that optogenetic astrocytic activation improves decision-making performance and engages ACC phase locking and BLA-to-ACC information flow. Collectively, these observations support the idea of an "astrocyte-neuron L-lactate shuttle'' and suggest that targeting astrocytes may help with cognitive dysfunctions under chronic visceral pain.