Development of Long-Term Dendritic Spine Stability in Diverse Regions of Cerebral Cortex

Abstract

Synapse formation and elimination occur throughout life, but the magnitude of such changes at distinct developmental stages remains unclear. Using transgenic mice overexpressing yellow fluorescent protein and transcranial two-photon microscopy, we repeatedly imaged dendritic spines on the apical dendrites of layer 5 pyramidal neurons. In young adolescent mice (1-month-old), 13%-20% of spines were eliminated and 5%-8% formed over 2 weeks in barrel, motor, and frontal cortices, indicating a cortical-wide spine loss during this developmental period. As animals mature, there is also a substantial loss of dendritic filopodia involved in spinogenesis. In adult mice (4-6 months old), 3%-5% of spines were eliminated and formed over 2 weeks in various cortical regions. Over 18 months, only 26% of spines were eliminated and 19% formed in adult barrel cortex. Thus, after a concurrent loss of spines and spine precursors in diverse regions of young adolescent cortex, spines become stable and a majority of them can last throughout life.

Two-photon imaging of synaptic plasticity and pathology in the living mouse brain

“…They also showed that in adult barrel cortex, Ͼ70% of spines are persistent over an 18-month interval, underscoring the remarkable stability of dendritic spines in adulthood and their potential role in long-term information storage. 34 A recent study examining spine dynamics in the visual, somatosensory, and auditory cortices in ϳ2 month-old mice found that Ͼ80% of spines are stable over 3 weeks, 35 in agreement with the view that adult spines are largely stable.…”

“…Although this newer study showed the majority of adult spines can be stable over weeks, more than 20% of total spines in 6-months-old mice are still considered transient and persist less than 4 days. 33 On the other hand, Zuo et al 34 showed that in adults (Ͼ 4 months old), spines exhibited similar low rates of elimination and formation in barrel, primary motor, and frontal cortices as their previously reported low turnover rates in the primary visual cortex. They also showed that in adult barrel cortex, Ͼ70% of spines are persistent over an 18-month interval, underscoring the remarkable stability of dendritic spines in adulthood and their potential role in long-term information storage.…”

“…In general, studies that used a minimally invasive method consisting of imaging through a thinned skull preparation tended to show very low degree of dendritic spine plasticity. 21,34 In contrast, studies imaging through a cranial window, which involves removal of a piece of skull ϳ5 mm in diameter, and covering the exposed brain with agarose and a glass coverslip 22,33 showed much greater degrees of dendritic dynamism. In the latter case, imaging usually starts 7 to 10 days after placing the cranial window.…”

“…In such cases, the thinning process generally leads to mild neuronal injury, mainly manifested by axonal and dendritic blebbing, and eventual disappearance of fluorescent structures. 21,34 For easy detection of neuronal injury during the thinning process or cranial window implantation, it is therefore helpful to use transgenic mice in which neurons are densely labeled (YFP-H line 17 ) rather than mice with low neuronal labeling density (GFP-M line 17 ).…”

Multimodal imaging of mouse development: Tools for the postgenomic era

“…Multiple studies have used repeated imaging in the brain to document changes in dendritic spines in the neocortex (Konur and Yuste, 2004;Zuo et al, 2005). Both studies show that while spines are continually eliminated throughout early postnatal life, spines become more stable as the animal matures.…”