School of Physiology and Pharmacology, University of Bristol, University Walk, Bristol, BS8 1TD, UK.
Mol Brain. 2010 Nov 1;3:32. doi: 10.1186/1756-6606-3-32.
Aβ peptides derived from the cleavage of amyloid precursor protein are widely believed to play an important role in the pathophysiology of Alzheimer's disease. A common way to study the impact of these molecules on CNS function is to compare the physiology of transgenic mice that overproduce Aβ with non-transgenic animals. In the hippocampus, this approach has been frequently applied to the investigation of synaptic transmission and plasticity in the perforant and Schaffer collateral commissural pathways, the first and third components of the classical hippocampal trisynaptic circuit, respectively. Similar studies however have not been carried out on the remaining component of the trisynaptic circuit, the mossy fibre pathway. Using transverse hippocampal slices prepared from ~2 year old animals we have compared mossy fibre synaptic function in wild-type mice and their Tg2576 littermates which age-dependently overproduce Aβ. Input-output curves were not altered in slices from Tg2576 mice, but these animals exhibited a significant loss of the prominent frequency-facilitation expressed by the mossy fibre pathway. In addition to this change in short term synaptic plasticity, high frequency stimulation-induced, NMDA-receptor-independent LTP was absent in slices from the transgenic mice. These data represent the first description of functional deficits in the mossy fibre pathway of Aβ-overproducing transgenic mice.
β淀粉样肽来源于淀粉样前体蛋白的裂解，被广泛认为在阿尔茨海默病的病理生理学中发挥重要作用。研究这些分子对中枢神经系统功能影响的常用方法是比较过度产生β淀粉样肽的转基因小鼠与非转基因动物的生理学。在海马体中，这种方法常用于研究穿通和沙费尔侧枝联合径路（经典海马三突触回路的第一和第三部分）中的突触传递和可塑性。然而，在三突触回路的其余部分，即苔藓纤维通路中，尚未进行类似的研究。使用从~2 岁的动物制备的横向海马切片，我们比较了野生型小鼠和其年龄依赖性过度产生β淀粉样肽的 Tg2576 同窝仔鼠中的苔藓纤维突触功能。在 Tg2576 小鼠的切片中，输入-输出曲线没有改变，但这些动物表现出明显的苔藓纤维通路的突出频率易化丧失。除了这种短期突触可塑性的改变外，来自转基因小鼠的切片中不存在高频刺激诱导的 NMDA 受体非依赖性 LTP。这些数据代表了在过度产生β淀粉样肽的转基因小鼠中，苔藓纤维通路功能缺陷的首次描述。
