Butcher John B, Sims Robert E, Ngum Neville M, Bazzari Amjad H, Jenkins Stuart I, King Marianne, Hill Eric J, Nagel David A, Fox Kevin, Parri H Rheinallt, Glazewski Stanislaw
School of Life Sciences, Keele University, Keele, United Kingdom.
College of Health and Life Sciences, Aston University, Birmingham, United Kingdom.
Front Cell Neurosci. 2022 Aug 25;16:905285. doi: 10.3389/fncel.2022.905285. eCollection 2022.
Changes to sensory experience result in plasticity of synapses in the cortex. This experience-dependent plasticity (EDP) is a fundamental property of the brain. Yet, while much is known about neuronal roles in EDP, very little is known about the role of astrocytes. To address this issue, we used the well-described mouse whiskers-to-barrel cortex system, which expresses a number of forms of EDP. We found that all-whisker deprivation induced characteristic experience-dependent Hebbian depression (EDHD) followed by homeostatic upregulation in L2/3 barrel cortex of wild type mice. However, these changes were not seen in mutant animals (IPR2) that lack the astrocyte-expressed IP receptor subtype. A separate paradigm, the single-whisker experience, induced potentiation of whisker-induced response in both wild-type (WT) mice and IPR2 mice. Recordings in barrel cortex slices reflected the results so that long-term depression (LTD) could not be elicited in slices from IPR2 mice, but long-term potentiation (LTP) could. Interestingly, 1 Hz stimulation inducing LTD in WT paradoxically resulted in NMDAR-dependent LTP in slices from IPR2 animals. The LTD to LTP switch was mimicked by acute buffering astrocytic [Ca] in WT slices. Both WT LTD and IPR2 1 Hz LTP were mediated by non-ionotropic NMDAR signaling, but only WT LTD was P38 MAPK dependent, indicating an underlying mechanistic switch. These results demonstrate a critical role for astrocytic [Ca] in several EDP mechanisms in neocortex.
感觉体验的变化会导致皮质中突触的可塑性。这种依赖于经验的可塑性（EDP）是大脑的一项基本特性。然而，尽管我们对EDP中神经元的作用了解很多，但对星形胶质细胞的作用却知之甚少。为了解决这个问题，我们使用了描述详尽的小鼠胡须到桶状皮质系统，该系统表现出多种形式的EDP。我们发现，全胡须剥夺会在野生型小鼠的L2/3桶状皮质中诱导出特征性的依赖于经验的赫布式抑制（EDHD），随后是稳态上调。然而，在缺乏星形胶质细胞表达的IP受体亚型的突变动物（IPR2）中未观察到这些变化。另一种模式，即单胡须体验，在野生型（WT）小鼠和IPR2小鼠中均诱导了胡须诱导反应的增强。桶状皮质切片中的记录反映了这一结果，即IPR2小鼠的切片中无法诱发长时程抑制（LTD），但可以诱发长时程增强（LTP）。有趣的是，在WT中诱导LTD的1 Hz刺激在IPR2动物的切片中反而导致了依赖于NMDAR的LTP。在WT切片中急性缓冲星形胶质细胞的[Ca]可模拟LTD到LTP的转换。WT LTD和IPR2 1 Hz LTP均由非离子型NMDAR信号介导，但只有WT LTD依赖于P38 MAPK，这表明存在潜在的机制转换。这些结果证明了星形胶质细胞的[Ca]在新皮质的几种EDP机制中起关键作用。
