Centro De Neurobiología Y Plasticidad Cerebral CNPC, Instituto De Fisiología, Facultad De Ciencias, Universidad De Valparaíso, Chile.
Departamento De Biología Celular, Centro De Microscopía Avanzada CMA BIOBIO, Facultad De Ciencias Biológicas, Universidad De Concepción, Concepción, Chile.
Glia. 2015 Sep;63(9):1507-21. doi: 10.1002/glia.22817. Epub 2015 May 15.
The fine-tuning of synaptic transmission by astrocyte signaling is crucial to CNS physiology. However, how exactly astroglial excitability and gliotransmission are affected in several neuropathologies, including epilepsy, remains unclear. Here, using a chronic model of temporal lobe epilepsy (TLE) in rats, we found that astrocytes from astrogliotic hippocampal slices displayed an augmented incidence of TTX-insensitive spontaneous slow Ca(2+) transients (STs), suggesting a hyperexcitable pattern of astroglial activity. As a consequence, elevated glutamate-mediated gliotransmission, observed as increased slow inward current (SICs) frequency, up-regulates the probability of neurotransmitter release in CA3-CA1 synapses. Selective blockade of spontaneous astroglial Ca(2+) elevations as well as the inhibition of purinergic P2Y1 or mGluR5 receptors relieves the abnormal enhancement of synaptic strength. Moreover, mGluR5 blockade eliminates any synaptic effects induced by P2Y1R inhibition alone, suggesting that the Pr modulation via mGluR occurs downstream of P2Y1R-mediated Ca(2+)-dependent glutamate release from astrocyte. Our findings show that elevated Ca(2+)-dependent glutamate gliotransmission from hyperexcitable astrocytes up-regulates excitatory neurotransmission in epileptic hippocampus, suggesting that gliotransmission should be considered as a novel functional key in a broad spectrum of neuropathological conditions.
星形胶质细胞信号对突触传递的精细调节对中枢神经系统生理学至关重要。然而，星形胶质细胞兴奋性和神经胶质传递在几种神经病理学中，包括癫痫，如何受到确切影响仍不清楚。在这里，我们使用大鼠颞叶癫痫（TLE）的慢性模型发现，星形胶质细胞来自星形胶质细胞增生的海马切片显示出 TTX 不敏感的自发缓慢 Ca(2+)瞬变 (ST) 的发生率增加，表明星形胶质细胞活性的超兴奋性模式。因此，升高的谷氨酸介导的神经胶质传递，表现为增加的缓慢内向电流 (SIC) 频率，上调 CA3-CA1 突触中神经递质释放的概率。选择性阻断自发星形胶质细胞 Ca(2+)升高以及嘌呤能 P2Y1 或 mGluR5 受体的抑制可减轻异常增强的突触强度。此外，mGluR5 阻断消除了单独抑制 P2Y1R 引起的任何突触效应，表明通过 mGluR 发生的 Pr 调制发生在 P2Y1R 介导的 Ca(2+)依赖性星形胶质细胞谷氨酸释放之后。我们的研究结果表明，来自超兴奋性星形胶质细胞的升高的 Ca(2+)依赖性谷氨酸神经胶质传递上调癫痫海马中的兴奋性神经传递，表明神经胶质传递应被视为广泛的神经病理学条件下的一种新的功能关键。
