Altered Synaptic Dynamics during Normal Brain Aging

Abstract

What is the neuroanatomical basis for the decline in brain function that occurs during normal aging? Previous postmortem studies have blamed it on a reduction in spine density, though results remain controversial and spine dynamics were not assessed. We used chronic in vivo two-photon imaging of dendritic spines and axonal boutons in somatosensory cortex for up to 1 year in thy1 GFP mice to test the hypothesis that aging is associated with alterations in synaptic dynamics. We find that the density of spines and en passant boutons (EPBs) in pyramidal cells increases throughout adult life but is stable between mature (8 -15 months) and old (Ͼ20 months) mice. However, new spines and EPBs are two to three times more likely to be stabilized over 30 d in old mice, although the long-term retention (over months) of stable spines is lower in old animals. In old mice, spines are smaller on average but are still able to make synaptic connections regardless of their size, as assessed by serial section electron microscopy reconstructions of previously imaged dendrites. Thus, our data suggest that age-related deficits in sensory perception are not associated with synapse loss in somatosensory cortex (as might be expected) butwithalterationsinthesizeandstabilityofspinesandboutonsobservedinthisbrainarea.Thechangeswedescribeherelikelyresultinweaker synapses that are less capable of short-term plasticity in aged individuals, and therefore to less efficient circuits.

Communication breakdown: The impact of ageing on synapse structure

“…Furthermore, there is an almost complete correlation between the increased volume of thin spines and reduced cognitive performance. However, in contrast to these findings, Mostany et al (2013) used chronic in vivo two-photon imaging of dendritic spines and axonal boutons in the somatosensory cortex, and find an abundance of thin spines only in juvenile mice (<1 month), while ratios of stubby, thin, and mushroom spines do not vary among young (3–5 months), mature (8–15 months) and old (>20 months) mice. They also find that there is no spine loss in old mice, but spines tend to be smaller, with less long-term retention of stable spines.…”

A synopsis on aging—Theories, mechanisms and future prospects

“…Another example is that of the somewhat widespread belief that there is a global neuron loss with age. In fact, the difference in total neuron number over the age range of 20–90 years is less than 10% (Pakkenberg et al, 2003; Pannese, 2011), though some morphological alterations do take place, such as significant decrease loss of synapses (Mostany et al, 2013), axon demyelination (Adamo, 2014) or loss of dendritic spines (Dickstein et al, 2013). …”

Homeostatic Plasticity of Subcellular Neuronal Structures: From Inputs to Outputs

“…Interestingly, a more recent study using two-photon microendoscopy to image pyramidal cell dendritic spines in the hippocampus showed a distinct lack of stable spines, all of them turning over with a mean lifetime of 1–2 weeks [74]. In addition, the developmental stage of the organism also affects spine turnover 40, 75, 76, such that younger animals have a much larger proportion of dynamic spines compared with the more stable spines found in adults.…”