Imaging of Experience-Dependent Structural Plasticity in the Mouse Neocortex in vivo

Abstract

The functionality of adult neocortical circuits can be altered by novel experiences or learning. This functional plasticity appears to rely on changes in the strength of neuronal connections that were established during development. Here we will describe studies in which we have addressed whether structural changes, including the remodeling of axons and dendrites with synapse formation and elimination, could underlie experience-dependent plasticity in the adult neocortex.Using 2-photon laser-scanning microscopy transgenic mice expressing GFP in a subset of pyramidal cells, we have observed that a small subset of dendritic spines continuously appear and disappear on a daily basis,whereas themajority of spines persists formonths. Axonal boutons fromdifferent neuronal classes displayed similar behavior, although the extent of remodeling varied. Under baseline conditions, new spines in the barrel cortex were mostly transient and rarely survived for more than a week. However, when every other whisker was trimmed (a paradigm known to induce adaptive functional changes in barrel cortex), the generation and loss of persistent spines was enhanced. Ultrastructural reconstruction of previously imaged spines and boutons using serial section electron microscopy showed that new spines slowly formsynapses. New spines that persisted for a few days always had synapses, whereas very young spines often lacked synapses. New synapses were predominantly found on large, multisynapse boutons, suggesting that spine growth is followed by synapse formation, preferentially on existing boutons.Altogether our data indicate that novel sensory experience drives the stabilization of new spines on subclasses of cortical neurons and promotes the formation of new synapses. These synaptic changes likely underlie experience-dependent functional remodeling of specific neocortical circuits.