Astrocyte and Neuronal Panx1 Support Long-Term Reference Memory in Mice.

IF 3.9 4区 医学 Q2 NEUROSCIENCES
Price Obot, Galadu Subah, Antonia Schonwald, Jian Pan, Libor Velíšek, Jana Velíšková, Patric K Stanton, Eliana Scemes
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引用次数: 0

Abstract

Pannexin 1 (Panx1) is an ubiquitously expressed protein that forms plasma membrane channels permeable to anions and moderate-sized signaling molecules (e.g., ATP, glutamate). In the nervous system, activation of Panx1 channels has been extensively shown to contribute to distinct neurological disorders (epilepsy, chronic pain, migraine, neuroAIDS, etc.), but knowledge of the extent to which these channels have a physiological role remains restricted to three studies supporting their involvement in hippocampus dependent learning. Given that Panx1 channels may provide an important mechanism for activity-dependent neuron-glia interaction, we used Panx1 transgenic mice with global and cell-type specific deletions of Panx1 to interrogate their participation in working and reference memory. Using the eight-arm radial maze, we show that long-term spatial reference memory, but not spatial working memory, is deficient in Panx1-null mice and that both astrocyte and neuronal Panx1 contribute to the consolidation of long-term spatial memory. Field potential recordings in hippocampal slices of Panx1-null mice revealed an attenuation of both long-term potentiation (LTP) of synaptic strength and long-term depression (LTD) at Schaffer collateral-CA1 synapses without alterations of basal synaptic transmission or pre-synaptic paired-pulse facilitation. Our results implicate both neuronal and astrocyte Panx1 channels as critical players for the development and maintenance of long-term spatial reference memory in mice.

星形胶质细胞和神经元Panx1支持小鼠长期参考记忆。
Pannexin 1 (Panx1)是一种普遍表达的蛋白,可形成可渗透阴离子和中等大小信号分子(如ATP,谷氨酸)的质膜通道。在神经系统中,Panx1通道的激活已被广泛证明有助于不同的神经系统疾病(癫痫、慢性疼痛、偏头痛、神经艾滋病等),但关于这些通道在多大程度上具有生理作用的知识仍然局限于支持它们参与海马依赖学习的三项研究。鉴于Panx1通道可能为活动依赖性神经元-胶质细胞相互作用提供了重要的机制,我们使用Panx1转基因小鼠进行Panx1的整体缺失和细胞类型特异性缺失来研究它们在工作记忆和参考记忆中的参与。通过八臂放射状迷宫,我们发现Panx1缺失的小鼠存在长期空间参考记忆缺失,而不是空间工作记忆缺失,星形胶质细胞和神经元Panx1都有助于长期空间记忆的巩固。panx1缺失小鼠海马切片的场电位记录显示,Schaffer侧侧- ca1突触的突触强度长期增强(LTP)和长期抑制(LTD)均有所减弱,但基础突触传递和突触前成对脉冲促进作用未发生改变。我们的研究结果表明,神经元和星形胶质细胞Panx1通道在小鼠长期空间参考记忆的发展和维持中都起着关键作用。
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来源期刊
ASN NEURO
ASN NEURO NEUROSCIENCES-
CiteScore
7.70
自引率
4.30%
发文量
35
审稿时长
>12 weeks
期刊介绍: ASN NEURO is an open access, peer-reviewed journal uniquely positioned to provide investigators with the most recent advances across the breadth of the cellular and molecular neurosciences. The official journal of the American Society for Neurochemistry, ASN NEURO is dedicated to the promotion, support, and facilitation of communication among cellular and molecular neuroscientists of all specializations.
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