Environmental enrichment enhances precision and remodeling speed of synaptic nanoarchitecture revealed by crosstalk free two-color in vivo STED nanoscopy
Synaptic plasticity underlies long-lasting structural and functional changes to brain circuitry and its experience-dependent remodeling can be fundamentally enhanced by environmental enrichment. It is unknown, however, whether and how environmental enrichment alters the morphology and dynamics of individual synapses. Here, we present a virtually crosstalk free, two-color in vivo STED microscope to simultaneously superresolve the dynamics of endogenous PSD95 of the post-synaptic density and spine geometry. With environmental enrichment, the size distributions of PSD95 and spine head sizes were sharper than in controls, indicating that synaptic strength is set more precisely with environmental enrichment. Spine head geometry and PSD95 assemblies were highly dynamic but their changes correlated only mildly. With environmental enrichment, the topography of the PSD95 nanoorganization was more dynamic; changes in size were smaller than in mice housed in standard cages and depended linearly on their original size. Thus, two-color in vivo time-lapse imaging of synaptic nanoorganization uncovers a unique synaptic nanoplasticity associated with the enhanced learning capabilities under environmental enrichment.