Effects of amyloid-β plaque proximity on the axon initial segment of pyramidal cells

Journal of Alzheimer's Disease : JAD
Gonzalo León-EspinosaAlberto Muñoz

Abstract

The output of cortical pyramidal cells reflects the balance between excitatory inputs of cortical and subcortical origin, and inhibitory inputs from distinct populations of cortical GABAergic interneurons, each of which selectively innervate different domains of neuronal pyramidal cells (i.e., dendrites, soma and axon initial segment [AIS]). In Alzheimer's disease (AD), the presence of amyloid-β (Aβ) plaques alters the synaptic input to pyramidal cells in a number of ways. However, the effects of Aβ plaques on the AIS have still not been investigated to date. This neuronal domain is involved in input integration, as well as action potential initiation and propagation, and it exhibits Ca2+- and activity-dependent structural plasticity. The AIS is innervated by GABAergic axon terminals from chandelier cells, which are thought to exert a strong influence on pyramidal cell output. In the AβPP/PS1 transgenic mouse model of AD, we have investigated the effects of Aβ plaques on the morphological and neurochemical features of the AIS, including the cisternal organelle, using immunocytochemistry and confocal microscopy, as well as studying the innervation of the AIS by chandelier cell axon terminals. There is a strong reduction in GABAe...Continue Reading

Citations

Dec 13, 2012·Stroke; a Journal of Cerebral Circulation·Jason D HinmanS Thomas Carmichael
Sep 17, 2018·Brain Structure & Function·Gonzalo León-EspinosaAlberto Muñoz
Nov 6, 2015·The Journal of Physiology·Txomin LalanneP Jesper Sjöström
Dec 13, 2017·ASN Neuro·Kareem ClarkJeffrey L Dupree
Apr 26, 2016·Experimental Neurology·Miguel A MarinMatthew N Rasband

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