201. β-Amyloid triggers aberrant over-scaling of homeostatic synaptic plasticity
- Author
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James Gilbert, Youming Lu, Ling-Qiang Zhu, Heng-Ye Man, Shu Shu, and Xin Yang
- Subjects
0301 basic medicine ,Synaptic scaling ,Amyloid beta ,musculoskeletal, neural, and ocular physiology ,Nonsynaptic plasticity ,AMPA receptor ,Biology ,Pathology and Forensic Medicine ,Cell biology ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,030104 developmental biology ,0302 clinical medicine ,Synaptic fatigue ,nervous system ,Homeostatic plasticity ,Synaptic plasticity ,Metaplasticity ,biology.protein ,Neurology (clinical) ,Neuroscience ,030217 neurology & neurosurgery - Abstract
The over-production of β-amyloid (Aβ) has been strongly correlated to neuronal dysfunction and altered synaptic plasticity in Alzheimer’s disease (AD). Accordingly, it has been proposed that disrupted synaptic transmission and neuronal network instability underlie memory failure that is evident in the early phases of AD. Homeostatic synaptic plasticity (HSP) serves to restrain neuronal activity within a physiological range. Therefore a disruption of this mechanism may lead to destabilization in synaptic and neural circuit function. Here, we report that during HSP by neuronal activity deprivation, application of Aβ results in an aberrant over-response of the up-regulation of AMPA receptor (AMPAR)-mediated synaptic currents and cell-surface AMPAR expression. In the visual cortex, in vivo HSP induced by visual deprivation shows a similar over-response following an Aβ local injection. Aβ increases the expression of GluA2-lacking, calcium permeable AMPARs (CP-AMPARs), which are required for the initiation, but not maintenance of HSP. Both GluA2-lacking and GluA2-containing AMPARs contribute to the Aβ-mediated over-scaling of HSP. We also find that Aβ induces the dissociation of HDAC1 from the miR124 transcription factor EVI1, leading to an up-regulation of miR124 expression and increased amount of CP-AMPARs. Thus, via aberrant stimulation of miR124 expression and biogenesis of CP-AMPARs, Aβ is able to induce an over response in HSP. This Aβ-mediated dysregulation in homeostatic plasticity may play an important role in the pathogenesis of altered neural function and memory deficits in the early stages of AD.
- Published
- 2016