■虽然阿尔茨海默病(AD)已被广泛研究,重点是认知网络,尽管有令人信服的证据表明视觉网络功能障碍在AD患者和小鼠模型中具有重要意义,但其受到的关注较少.我们最近报道了淀粉样蛋白斑块前AD模型的初级视觉皮层中的c-Fos和突触失调。
■我们测试了AD模型中皮质和皮质下视区域的c-Fos表达和突触前密度/动力学是否不同。我们还检查了异常的c-Fos表达是否通过功能连接继承并通过光经验塑造。
■c-Fos+细胞密度,功能连接,在4-6个月大的J20(AD模型)和野生型(WT)小鼠的两种性别中,对其视觉和全脑网络进行了评估。使用离体和体内成像比较了AD模型中突触前脆弱性的皮质和皮质下差异。
■视觉皮层,但不是皮质下,网络显示异常的c-Fos表达和受损的经验依赖性调制。WT小鼠大脑区域的平均功能连接显着预测c-Fos表达异常,这与AD模型中受损的经验依赖性调制相关。我们观察到兴奋性视觉皮层突触的微妙而选择性的减弱。与WT小鼠相比,AD模型中皮质boutons的大小分布缩小了,暗示了对布顿大小的突触缩放样适应。
■视觉网络结构和功能破坏偏向斑块前J20小鼠的皮质区域,AD模型中的细胞和突触失调表示在WT条件下观察到的基线生理学的不适应改变。
UNASSIGNED: While Alzheimer\'s disease (AD) has been extensively studied with a focus on cognitive networks, visual network dysfunction has received less attention despite compelling evidence of its significance in AD patients and mouse models. We recently reported c-Fos and synaptic dysregulation in the primary visual cortex of a pre-amyloid plaque AD-model.
UNASSIGNED: We test whether c-Fos expression and presynaptic density/dynamics differ in cortical and subcortical visual areas in an AD-model. We also examine whether aberrant c-Fos expression is inherited through functional connectivity and shaped by light experience.
UNASSIGNED: c-Fos+ cell density, functional connectivity, and their experience-dependent modulation were assessed for visual and whole-brain networks in both sexes of 4-6-month-old J20 (AD-model) and wildtype (WT) mice. Cortical and subcortical differences in presynaptic vulnerability in the AD-model were compared using ex vivo and in vivo imaging.
UNASSIGNED: Visual cortical, but not subcortical, networks show aberrant c-Fos expression and impaired experience-dependent modulation. The average functional connectivity of a brain region in WT mice significantly predicts aberrant c-Fos expression, which correlates with impaired experience-dependent modulation in the AD-model. We observed a subtle yet selective weakening of excitatory visual cortical synapses. The size distribution of cortical boutons in the AD-model is downscaled relative to those in WT mice, suggesting a synaptic scaling-like adaptation of bouton size.
UNASSIGNED: Visual network structural and functional disruptions are biased toward cortical regions in pre-plaque J20 mice, and the cellular and synaptic dysregulation in the AD-model represents a maladaptive modification of the baseline physiology seen in WT conditions.