In vivo volume dynamics of dendritic spines in the neocortex of wild-type and Fmr1 KO mice

Abstract

Excitatory synapses are often formed at small protrusions of dendrite, called dendritic spines, in most projection neurons, and the spine-head volumes show strong correlations with synaptic connectivity. We examined the dynamics of spine volume in the adult mouse visual cortex using time-lapse in vivo two-photon imaging with a resonant Galvano scanner. Contrary to expectations, we found that the spines in the adult neocortex showed fluctuations to a similar degree as that observed in young hippocampal preparations, but there were systematic differences in how the dynamics were dependent on spine volumes, thus allowing for fewer fluctuations in small spines, which could account for the relatively low turnover rates of neocortical spines in vivo. We found that spine volumes fluctuated to a greater extent in a mouse model (Fmr1 knockout) of fragile X mental retardation than in wild-type mice, and the spine turnover rates were also higher in Fmr1 knockout mice. Such features of spine dynamics in Fmr1 knockout mice could be represented by a single slope factor in our model. Our data and model indicate a small but significant change in the average spine volume and more eminent differences in the statistical distribution in Fmr1 knockout mice even in adulthood, which reflects the abnormal in vivo dynamics of spine volumes.

Significance Statement Excitatory synapses are often formed at dendritic spines in projection neurons, and the spine volumes show strong correlations with synaptic connectivity. We studied the dynamics of spine volumes in vivo using a resonant scanner two-photon microscope, and found that spine dynamics showed a distinctive dependence on spine volume in the adult neocortex, allowing for fewer fluctuations in these small spines than in the spines of young hippocampi. Moreover, the dynamics of spine volumes explained the greater turnover rate of spines and the smaller spine volume observed in a mouse model (Fmr1 knockout) of fragile X syndrome mental retardation than in wild-type mice. Our results indicate that the dynamics of spine volumes are abnormal in Fmr1 KO mice, even in adulthood.