AbstractThe developing brain can respond quickly to altered sensory experience by circuit reorganization. During a critical period in early life, neurons in the primary visual cortex rapidly lose responsiveness to an occluded eye and come to respond better to the open eye. While physiological and some of the molecular mechanisms of this process have been characterized, its structural basis, except for the well-known changes in the thalamocortical projection, remains obscure. To elucidate the relationship between synaptic remodeling and functional changes during this experience-dependent process, we used 2-photon microscopy to image synaptic structures of sparsely labeled layer 2/3 neurons in the binocular zone of mouse primary visual cortex. Anatomical changes at presynaptic and postsynaptic sites in mice undergoing monocular visual deprivation (MD) were compared to those in control mice with normal visual experience. We found that postsynaptic spines remodeled quickly in response to MD, with neurons more strongly dominated by the deprived eye losing more spines. These postsynaptic changes parallel changes in visual responses during MD and their recovery after restoration of binocular vision. In control animals with normal visual experience, the formation of presynaptic boutons increased during the critical period and then declined. MD affected bouton formation, but with a delay, blocking it after 3 days. These findings reveal intracortical anatomical changes in cellular layers of the cortex that can account for rapid activity-dependent plasticity.Significance statementThe operation of the cortex depends on the connections among its neurons. Taking advantage of molecular and genetic tools to label major proteins of the presynaptic and postsynaptic densities, we studied how connections of layer 2/3 excitatory neurons in mouse visual cortex were changed by monocular visual deprivation during the critical period, which causes amblyopia. The deprivation induced rapid remodeling of postsynaptic spines and impaired bouton formation. Structural measurement followed by calcium imaging demonstrated a strong correlation between changes in postsynaptic structures and functional responses in individual neurons after monocular deprivation. These findings suggest that anatomical changes at postsynaptic sites serve as a substrate for experience-dependent plasticity in the developing visual cortex.
Anatomical changes to primary visual cortex in the congenital absence of cone input
