The diverse roles of complex glycans in synapse development and function

Protein glycosylation is a critical post-translational modification that mediates a myriad of biological functions, including neuronal development in the brain. Stages of neuronal development include neurogenesis, neuronal migration, axonal guidance, synapse formation, and activity-dependent synaptic remodeling and plasticity. Among these, synapse formation and plasticity are essential to establish and maintain neuronal circuits for proper brain function. Yet, the physiological role of glycans at synapses remains poorly understood. This is especially true for complex glycans, known for decades to be present on the cell surface or extracellular matrix, including the microenvironment around synapses. In this review, we highlight recent examples of complex glycans to illustrate their roles in synapse formation and function. Based on these advances, we propose three principal models to categorize all examples in our discussion. We hope this will be beneficial for the field to begin a discussion on the conceptual framework underlying the role of glycans at synapses.