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Publication : Tau and amyloid-related pathologies in the entorhinal cortex have divergent effects in the hippocampal circuit.

First Author  Angulo SL Year  2017
Journal  Neurobiol Dis Volume  108
Pages  261-276 PubMed ID  28860088
Mgi Jnum  J:258530 Mgi Id  MGI:6142076
Doi  10.1016/j.nbd.2017.08.015 Citation  Angulo SL, et al. (2017) Tau and amyloid-related pathologies in the entorhinal cortex have divergent effects in the hippocampal circuit. Neurobiol Dis 108:261-276
abstractText  The entorhinal cortex (EC) is affected early in Alzheimer''s disease, an illness defined by a co-occurrence of tau and amyloid-related pathologies. How the co-occurrence of these pathologies in the EC affects the hippocampal circuit remains unknown. Here we address this question by performing electrophysiological analyses of the EC circuit in mice that express mutant human amyloid precursor protein (hAPP) or tau (hTau), or both in the EC. We show that the alterations in the hippocampal circuit are divergent, with hAPP increasing but hTau decreasing neuronal/circuit excitability. Most importantly, mice co-expressing hAPP and hTau show that hTau has a dominant effect, dampening the excitatory effects of hAPP. Additionally, compensatory synaptic downscaling, in response to increased excitability in EC was observed in subicular neurons of hAPP mice. Based on simulations, we propose that EC interneuron pruning can account for both EC hyperexcitability and subicular synaptic downscaling found in mice expressing hAPP.
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