Department of Biomedical Sciences, Colorado State University, 1617 Campus Delivery, Fort Collins, CO 80523, USA.
Department of Biomedical Sciences, Colorado State University, 1617 Campus Delivery, Fort Collins, CO 80523, USA.
Cell Rep. 2018 Jul 10;24(2):342-354. doi: 10.1016/j.celrep.2018.06.029.
Homeostatic synaptic plasticity (HSP) is the ability of neurons to exert compensatory changes in response to altered neural activity. How pathologically induced activity changes are intertwined with HSP mechanisms is unclear. We show that, in cholinergic neurons from Drosophila, beta-amyloid (Aβ) peptides Aβ40 and Aβ42 both induce an increase in spontaneous activity. In a transgenic line expressing Aβ42, we observe that this early increase in spontaneous activity is followed by a dramatic reduction in spontaneous events, a progression that has been suggested to occur in cholinergic brain regions of mammalian models of Alzheimer's disease. We present evidence that the early enhancement in synaptic activity is mediated by the Drosophila α7 nicotinic acetylcholine receptor (nAChR) and that, later, Aβ42-induced inhibition of synaptic events is a consequence of Dα7-dependent HSP mechanisms induced by earlier hyperactivity. Thus, while HSP may initially be an adaptive response, it may also drive maladaptive changes and downstream pathologies.
稳态突触可塑性（HSP）是神经元在神经活动改变时产生代偿性变化的能力。病理性诱导的活动变化与 HSP 机制如何交织在一起尚不清楚。我们表明，在果蝇的胆碱能神经元中，β-淀粉样蛋白（Aβ）肽 Aβ40 和 Aβ42 均诱导自发活动增加。在表达 Aβ42 的转基因系中，我们观察到自发活动的这种早期增加之后是自发事件的急剧减少，这种进展据推测发生在阿尔茨海默病的哺乳动物模型的胆碱能脑区。我们提出的证据表明，突触活动的早期增强是由果蝇α7 烟碱型乙酰胆碱受体（nAChR）介导的，而后来，Aβ42 诱导的突触事件抑制是由早期过度兴奋引起的 Dα7 依赖性 HSP 机制的后果。因此，虽然 HSP 最初可能是一种适应性反应，但它也可能导致适应不良的变化和下游病理。
