Increased axonal bouton dynamics in the aging mouse cortex

Federico W. Grillo, Sen Song, Leonor M. Teles-Grilo Ruivo, Lieven Huang, Ge Gao, Graham W. Knott, Bohumil Maco, Valentina Ferretti, Dawn Thompson, Graham E. Little, Vincenzo De Paola

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91 Citations (Scopus)


Aging is a major risk factor for many neurological diseases and is associated with mild cognitive decline. Previous studies suggest that aging is accompanied by reduced synapse number and synaptic plasticity in specific brain regions. However, most studies, to date, used either postmortem or ex vivo preparations and lacked key in vivo evidence. Thus, whether neuronal arbors and synaptic structures remain dynamic in the intact aged brain and whether specific synaptic deficits arise during aging remains unknown. Here we used in vivo two-photon imaging and a unique analysis method to rigorously measure and track the size and location of axonal boutons in aged mice. Unexpectedly, the aged cortex shows circuit-specific increased rates of axonal bouton formation, elimination, and destabilization. Compared with the young adult brain, large (i.e., strong) boutons show 10-fold higher rates of destabilization and 20-fold higher turnover in the aged cortex. Size fluctuations of persistent boutons, believed to encode long-term memories, also are larger in the aged brain, whereas bouton size and density are not affected. Our data uncover a striking and unexpected increase in axonal bouton dynamics in the aged cortex. The increased turnover and destabilization rates of large boutons indicate that learning and memory deficits in the aged brain arise not through an inability to form new synapses but rather through decreased synaptic tenacity. Overall our study suggests that increased synaptic structural dynamics in specific cortical circuits may be a mechanism for age-related cognitive decline.

Original languageEnglish
Pages (from-to)E1514-E1523
Number of pages10
Issue number16
Early online date29 Mar 2013
Publication statusPublished - 16 Apr 2013

Bibliographical note

We thank Karel Svoboda for support and for critical input on the initial development of EPBscore; Anthony Holtmaat and Linda Wilbrecht for help with an initial set of experiments; Peter Bloomfield for help with the TB analysis; the Medical Research Council Clinical Sciences Centre microscopy facility and Keng Imm Hng for help with the immunohistochemical analysis; Marco Cantoni for his help with the FIBSEM imaging; and Roberto Fiore for comments on the manuscript. S.S. is supported by National Science Foundation of China Grant 20111300429 and by the Open Research Fund of the State Key Laboratory of Cognitive Neuroscience and Learning. This work was funded by the Medical Research Council.

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  • neural circuits
  • ageing
  • structural plasticity
  • axon
  • in vivo imaging


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