A key feature of neurotransmission is its ability to adapt to changes in neuronal environment, which is essential for many brain functions. Homeostatic synaptic plasticity (HSP) emerges as a compensatory mechanism used by neurons to adjust their excitability in response to changes in synaptic activity. Recently, glial cells emerged as modulators for neurotransmission by releasing gliotransmitters into the synaptic cleft through pathways that include P2X7 receptors (P2X7R), connexons, and pannexons. However, the role of gliotransmission in the activity-dependent adjustment of presynaptic strength is still an open question. Here, we investigated whether glial cells participate in HSP upon chronic inactivity and the role of adenosine triphosphate (ATP), connexin43 hemichannels (Cx43HCs), and pannexin1 (Panx1) channels in this process. We used immunocytochemistry against vesicular glutamate transporter 1 (vGlut1) to estimate changes in synaptic strength in hippocampal dissociated cultures. Pharmacological manipulations indicate that glial-derived ATP and P2X7R are required for HSP. In addition, inhibition of Cx43 and Panx1 channels reveals a pivotal role for these channels in the compensatory adjustment of synaptic strength, emerging as new pathways for ATP release upon inactivity. The involvement of Panx1 channels was confirmed by using Panx1-deficient animals. Lacking Panx1 in neurons is sufficient to prevent the P2X7R-dependent upregulation of presynaptic strength; however, the P2X7R-dependent compensatory adjustment of synapse density requires both neuronal and glial Panx1. Together, our data supports an essential role for glial ATP signaling and Cx43HCs and Panx1 channels in the homeostatic adjustment of synaptic strength in hippocampal cultures upon chronic inactivity.

中文翻译：

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胶质细胞ATP和大的毛孔通道调节对慢性缺乏反应的突触强度。

神经传递的关键特征是其适应神经环境变化的能力，这对于许多大脑功能至关重要。稳态突触可塑性（HSP）作为神经元用来调节其兴奋性以响应突触活动变化的一种补偿机制而出现。最近，神经胶质细胞通过将神经胶质递质通过包括P2X7受体（P2X7R），连接子和pannexon的途径释放到突触间隙中而成为神经传递的调节剂。然而，神经胶质传递在突触前强度的活动依赖性调节中的作用仍然是一个悬而未决的问题。在这里，我们调查了神经胶质细胞是否因慢性不活动而参与HSP以及三磷酸腺苷（ATP），连接蛋白43半通道（Cx43HCs）和pannexin1（Panx1）通道在此过程中的作用。我们使用针对囊泡谷氨酸转运蛋白1（vGlut1）的免疫细胞化学来评估海马分离培养物中突触强度的变化。药理操作表明，HSP需要神经胶质衍生的ATP和P2X7R。此外，Cx43和Panx1通道的抑制作用揭示了这些通道在突触强度的补偿性调节中的关键作用，这是无活动时ATP释放的新途径。Panx1通道的参与已通过使用Panx1缺陷动物得到证实。神经元缺乏Panx1足以阻止P2X7R依赖的突触前强度上调；但是，依赖P2X7R的突触密度的补偿性调节需要神经元和神经胶质Panx1。一起，