Interneuron Simplification and Loss of Structural Plasticity As Markers of Aging-Related Functional Decline
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8421.full.pdf
Description
Published version
Size
1.22 MB
Format
Adobe PDF
Checksum (MD5)
a90b11ac0dc649eacf7002101109e6a5
Author(s)
Eavri, Ronen
Shepherd, Jason Dennis
Welsh, Christina A.
Flanders, Genevieve
Bear, Mark
Nedivi, Elly
Date Issued
August 2018
Journal
Journal of Neuroscience
Publisher
Society for Neuroscience
Citation
Eavri, Ronen et al. "Interneuron Simplification and Loss of Structural Plasticity As Markers of Aging-Related Functional Decline." Journal of Neuroscience 38, 39 (August 2018): 8421-8432. © 2018 The Author(s)
Version
Final published version
Abstract
Changes in excitatory neuron and synapse structure have been recognized as a potential physical source of age-related cognitive decline. Despite the importance of inhibition to brain plasticity, little is known regarding aging-associated changes to inhibitory neurons. Here we test for age-related cellular and circuit changes to inhibitory neurons of mouse visual cortex. We find no substantial difference in inhibitory neuron number, inhibitory neuronal subtypes, or synapse numbers within the cerebral cortex of aged mice compared with younger adults. However, when comparing cortical interneuron morphological parameters, we find differences in complexity, suggesting that arbors are simplified in aged mice. In vivo two-photon microscopy has previously shown that in contrast to pyramidal neurons, inhibitory interneurons retain a capacity for dendritic remodeling in the adult. We find that this capacity diminishes with age and is accompanied by a shift in dynamics from balanced branch additions and retractions to progressive prevalence of retractions, culminat-ingina dendritic arbor that is both simpler and more stable. Recording of visually evoked potentials shows that aging-related interneuron dendritic arbor simplification and reduced dynamics go hand in hand with loss of induced stimulus-selective response potentiation (SRP), a paradigm for adult visual cortical plasticity. Chronic treatment with the antidepressant fluoxetine reversed deficits in interneuron structural dynamics and restored SRP in aged animals. Our results support a structural basis for age-related impairments in sensory perception, and suggest that declines in inhibitory neuron structural plasticity during aging contribute to reduced functional plasticity.
MIT Department
Picower Institute for Learning and Memory
Massachusetts Institute of Technology. Department of Biology
Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1523/jneurosci.0808-18.2018
