Dendritic Spines of Layer 5 Pyramidal Neurons of the Aging Somatosensory Cortex Exhibit Reduced Volumetric Remodeling.

Impairments in synaptic dynamics and stability are observed both in neurodegenerative disorders and in the healthy aging cortex, which exhibits elevated dendritic spine turnover and decreased long-term stability of excitatory connections at baseline, as well as an altered response to plasticity induction. In addition to the discrete gain and loss of synapses, spines also change in size and strength both during learning and in the absence of neural activity, and synaptic volume has been associated with stability and incorporation into memory traces. Furthermore, intrinsic dynamics, an apparently stochastic component of spine volume changes, may serve as a homeostatic mechanism to prevent stabilization of superfluous connections. However, the effects of age on modulation of synaptic weights remain unknown. Using two-photon excitation (2PE) microscopy of spines during chemical plasticity induction in vitro and analyzing longitudinal in vivo 2PE images after a plasticity-inducing manipulation, we characterize the effects of age on volumetric changes of spines of the apical tuft of layer 5 pyramidal neurons of mouse primary somatosensory cortex. Aged mice exhibit decreased volumetric volatility and delayed rearrangement of synaptic weights of persistent connections, as well as greater susceptibility to spine shrinkage in response to chemical long-term depression. These results suggest a deficit in the aging brain's ability to fine-tune synaptic weights to properly incorporate and retain novel memories. This research provides the first evidence of alterations in spine volumetric dynamics in healthy aging and may support a model of impaired processing and learning in the aged somatosensory system.