Cocaine experience induces functional adaptations in astrocytes: Implications for synaptic plasticity in the nucleus accumbens shell.
Cocaine experience induces functional adaptations in astrocytes: Implications for synaptic plasticity in the nucleus accumbens shell.
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星形胶质细胞已成为大脑中神经元活动的重要调节因子。越来越多的文献表明，在啮齿类动物模型中，可卡因自我给药诱导星形胶质细胞内的结构变化，这可能影响它们与周围神经元的相互作用。在这里，我们提供的证据表明，可卡因影响星形胶质细胞的功能水平，并改变神经元的敏感性星形胶质细胞衍生的谷氨酸。我们报告说，一个为期14天的短期访问可卡因（2小时/天）减少自发星形胶质细胞钙瞬变和沉淀的变化，星形胶质细胞网络活动的核壳。这是伴随着缓慢的内向电流，神经元激活的星形胶质细胞谷氨酸的生理标志物，在一个子集的中型多刺神经元的增加的患病率。在这个子集内，但不是外部，我们观察到NMDA受体介导的突触事件的持续时间和频率增加。此外，我们发现突触NMDA受体可塑性和神经元对星形胶质细胞谷氨酸的敏感性之间的联系独立于药物暴露，并在可卡因和盐水对照动物中观察到。神经元Ca 2+活性的成像分析显示，可卡因自身给药对单个细胞或脑切片中的神经元网络活性没有影响。因此，我们的数据表明，可卡因自我管理促进星形胶质细胞特异性的功能变化，可以连接到谷氨酸介导的耦合与主神经元在延髓核。这种耦合可能在空间上受到限制，因为它不会对局部神经元回路的网络结构产生广泛影响。
Astrocytes have become established as an important regulator of neuronal activity in the brain. Accumulating literature demonstrates that cocaine self-administration in rodent models induces structural changes within astrocytes that may influence their interaction with the surrounding neurons. Here, we provide evidence that cocaine impacts astrocytes at the functional level and alters neuronal sensitivity to astrocyte-derived glutamate. We report that a fourteen-day period of short access to cocaine (2-hour/day) decreases spontaneous astrocytic Ca2+ transients and precipitates changes in astrocyte network activity in the nucleus accumbens shell. This is accompanied by increased prevalence of slow inward currents, a physiological marker of neuronal activation by astrocytic glutamate, in a subset of medium spiny neurons. Within, but not outside, of this subset, we observe an increase in duration and frequency of NMDA receptor-mediated synaptic events. Additionally, we find that the link between synaptic NMDA receptor plasticity and neuron sensitivity to astrocytic glutamate is maintained independent of drug exposure, and is observed in both cocaine and saline control animals. Imaging analyses of neuronal Ca2+ activity show no effect of cocaine self-administration at individual cells or on neuronal network activity in brain slices. Therefore, our data indicate that cocaine self-administration promotes astrocyte-specific functional changes that can be linked to increased glutamate-mediated coupling with principal neurons in the nucleus accumbens. Such coupling may be spatially restricted as it does not result in a broad impact on network structure of local neuronal circuits.
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