Role for astroglial α1-adrenoreceptors in gliotransmission and control of synaptic plasticity in the neocortex.
Role for astroglial α1-adrenoreceptors in gliotransmission and control of synaptic plasticity in the neocortex.
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DOI：
10.3389/fncel.2015.00230
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发表时间：
2015
影响因子：
5.3
通讯作者：
Lalo U
中科院分区：
文献类型：
--
作者：
Pankratov Y;Lalo U
神经细胞和神经胶质细胞之间的交流被认为对许多脑功能非常重要。星形胶质细胞通过释放胶质递质来调节突触强度。胶质传递的机制仍然不确定，胞吐作用是最有趣和有争议的途径。我们证明星形胶质α1-肾上腺素受体对去甲肾上腺素（NA）非常敏感，并在2/3层新皮质星形胶质细胞中对细胞内Ca2+信号传导有重要贡献。我们还发现星形胶质α1-肾上腺素受体在长时间暴露于NA后容易脱敏。我们发现，在新皮质切片中，α-1肾上腺素受体可以激活皮层星形胶质细胞的ATP和d -丝氨酸的囊状释放，从而在邻近的锥体神经元中引发ATP受体介导的电流爆发。这些嘌呤能电流可被星形胶质细胞内灌注破伤风毒素轻链抑制，证实其来源是星形胶质细胞胞吐。我们发现α1肾上腺素受体激活的胶质递质释放对于新皮层突触可塑性的诱导是重要的：α1肾上腺素受体拮抗剂特拉唑嗪可以消除新皮层兴奋性突触电位的长期增强（LTP）。我们发现，当星形胶质细胞额外被1 μ NA激活时，弱亚阈值θ -burst刺激（TBS）可以诱导LTP。这种促进作用依赖于神经元ATP受体的激活，在神经胶质胞吐受损的dn-SNARE小鼠的新皮质切片中被消除。重要的是，用破伤风毒素灌注单个星形细胞可显著降低NA对LTP的促进作用。我们的研究结果有力地支持星形胶质细胞肾上腺素能信号传导和胶质递质胞吐对突触传递和可塑性调节的生理重要性。
Communication between neuronal and glial cells is thought to be very important for many brain functions. Acting via release of gliotransmitters, astrocytes can modulate synaptic strength. The mechanisms underlying gliotransmission remain uncertain with exocytosis being the most intriguing and debated pathway. We demonstrate that astroglial α1-adrenoreceptors are very sensitive to noradrenaline (NA) and make a significant contribution to intracellular Ca2+-signaling in layer 2/3 neocortical astrocytes. We also show that astroglial α1-adrenoreceptors are prone to desensitization upon prolonged exposure to NA. We show that within neocortical slices, α-1adrenoreceptors can activate vesicular release of ATP and D-serine from cortical astrocytes which initiate a burst of ATP receptor-mediated currents in adjacent pyramidal neurons. These purinergic currents can be inhibited by intracellular perfusion of astrocytes with Tetanus Toxin light chain, verifying their origin via astroglial exocytosis. We show that α1 adrenoreceptor-activated release of gliotransmitters is important for the induction of synaptic plasticity in the neocortex:long-term potentiation (LTP) of neocortical excitatory synaptic potentials can be abolished by the selective α1-adrenoreceptor antagonist terazosin. We show that weak sub-threshold theta-burst stimulation (TBS) can induce LTP when astrocytes are additionally activated by 1 μM NA. This facilitation is dependent on the activation of neuronal ATP receptors and is abolished in neocortical slices from dn-SNARE mice which have impaired glial exocytosis. Importantly, facilitation of LTP by NA can be significantly reduced by perfusion of individual astrocytes with Tetanus Toxin. Our results strongly support the physiological importance of astroglial adrenergic signaling and exocytosis of gliotransmitters for modulation of synaptic transmission and plasticity.
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影响因子：
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