Dendritic Spine Elimination: Molecular Mechanisms and Implications

Abstract

Dynamic modification of synaptic connectivity in response to sensory experience is a vital step in the refinement of brain circuits as they are established during development and modified during learning. In addition to the well-established role for new spine growth and stabilization in the experience-dependent plasticity of neural circuits, dendritic spine elimination has been linked to improvements in learning, and dysregulation of spine elimination has been associated with intellectual disability and behavioral impairment. Proper brain function requires a tightly regulated balance between spine formation and spine elimination. Although most studies have focused on the mechanisms of spine formation, considerable progress has been made recently in delineating the neural activity patterns and downstream molecular mechanisms that drive dendritic spine elimination. Here, we review the current state of knowledge concerning the signaling pathways that drive dendritic spine shrinkage and elimination in the cerebral cortex and we discuss their implication in neuropsychiatric and neurodegenerative disease.