Structural remodeling of neural circuits via engineered neuro-glial interactions

The brain function is modulated by both rapid electrochemical activity of neurons and slow structural remodeling of synapses. Despite remarkable progress in controlling neural activity, methods for structural modulation of synaptic connections are still scarce. Here, we present a synthetic approach for synapse elimination via engineering of direct neuro-glial interactions which result in the uptake of synaptic components by astrocytes. The size-dependent synapse elimination in the CA3-CA1 circuit leads to a decline in synaptic connectivity, while the remaining synapses undergo reorganization of synaptic contents and increases in size and plasticity, contributing to memory enhancement. These findings provide an insight into how the brain adaptively shapes neural circuits upon synapse elimination and offer a versatile means to structurally modulate cell-cell connections.