Long-term dendritic spine stability in the adult cortex

Abstract

The structural dynamics of synapses probably has a crucial role in the development and plasticity of the nervous system. In the mammalian brain, the vast majority of excitatory axo-dendritic synapses occur on dendritic specializations called 'spines'. However, little is known about their long-term changes in the intact developing or adult animal. To address this question we developed a transcranial two-photon imaging technique to follow identified spines of layer-5 pyramidal neurons in the primary visual cortex of living transgenic mice expressing yellow fluorescent protein. Here we show that filopodia-like dendritic protrusions, extending and retracting over hours, are abundant in young animals but virtually absent from the adult. In young mice, within the 'critical period' for visual cortex development, approximately 73% of spines remain stable over a one-month interval; most changes are associated with spine elimination. In contrast, in adult mice, the overwhelming majority of spines (approximately 96%) remain stable over the same interval with a half-life greater than 13 months. These results indicate that spines, initially plastic during development, become remarkably stable in the adult, providing a potential structural basis for long-term information storage.

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

“…1). 21 In addition, this study also showed that in mice between 1 to 3 months of age, the rate of spine elimination is significantly higher than that of spine formation, leading to a net loss of spines during young adolescence. These results suggest that a significant percentage of spines in the mature adult mouse primary visual cortex can last throughout the lifespan of an animal and thus could provide a structural basis for lifelong information storage.…”

“…In particular, the advent of Green Flourescent Protein (GFP) and its spectral variants and the ability to generate transgenic mice or viral vectors to drive the expression of such proteins in specific cell types in the nervous system [17][18][19] are allowing for long-term imaging of individual synaptic structures at high resolution in living animals. 18,[20][21][22][23] The other major technical advance relates to better instrumentation for optical imaging of living tissues. Specifically, two-photon microscopy (TPM) has dra-matically enhanced the ability of deep tissue imaging.…”

Extracellular matrix inhibits structural and functional plasticity of dendritic spines in the adult visual cortex

“…6c). Filopodia are the telltale sign of spinogenesis, they are abundant during the critical period and disappear during circuitry maturation 25 . The density of filopodia in the adult control mice was only 0.016 ± 0.013 mm À 1 (s.d.…”

“…Morphological plasticity of dendritic spines tightly correlates with the level of cortical plasticity 23,24 . Indeed, during circuitry maturation, dendritic spines exhibit spontaneous motility and the formation of filopodial protusions heralds the emergence of novel excitatory synapses 25 . Later on, as the circuitry reaches its adult form, filopodia become very rare, spine motility subsides and connectivity stabilizes.…”

The 3 Rs of Stroke Biology: Radial, Relayed, and Regenerative

“…Dendritic spines form the synaptic contacts of cortical pyramidal neurons. These are mostly stable in the adult cortex [60,61], although they remodel in response to loss of afferent inputs or learning [62][63][64]. After stroke, there is initially a net loss of dendritic spines in peri-infarct cortex in the first week after stroke [52,65].…”