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Age-related dysregulation of homeostatic control in neuronal microcircuits

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Title: Age-related dysregulation of homeostatic control in neuronal microcircuits
Authors: Radulescu, CI
Doostdar, N
Zabouri, N
Melgosa-Ecenarro, L
Wang, X
Sadeh, S
Pavlidi, P
Airey, J
Kopanitsa, M
Clopath, C
Barnes, SJ
Item Type: Journal Article
Abstract: Neuronal homeostasis prevents hyperactivity and hypoactivity. Age-related hyperactivity suggests homeostasis may be dysregulated in later life. However, plasticity mechanisms preventing age-related hyperactivity and their efficacy in later life are unclear. We identify the adult cortical plasticity response to elevated activity driven by sensory overstimulation, then test how plasticity changes with age. We use in vivo two-photon imaging of calcium-mediated cellular/synaptic activity, electrophysiology and c-Fos-activity tagging to show control of neuronal activity is dysregulated in the visual cortex in late adulthood. Specifically, in young adult cortex, mGluR5-dependent population-wide excitatory synaptic weakening and inhibitory synaptogenesis reduce cortical activity following overstimulation. In later life, these mechanisms are downregulated, so that overstimulation results in synaptic strengthening and elevated activity. We also find overstimulation disrupts cognition in older but not younger animals. We propose that specific plasticity mechanisms fail in later life dysregulating neuronal microcircuit homeostasis and that the age-related response to overstimulation can impact cognitive performance.
Issue Date: Nov-2023
Date of Acceptance: 6-Sep-2023
URI: http://hdl.handle.net/10044/1/108074
DOI: 10.1038/s41593-023-01451-z
ISSN: 1097-6256
Publisher: Nature Research
Start Page: 2158
End Page: 2170
Journal / Book Title: Nature Neuroscience
Volume: 26
Issue: 11
Copyright Statement: © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.
Publication Status: Published
Conference Place: United States
Online Publication Date: 2023-11-02
Appears in Collections:Department of Brain Sciences



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