Structural modulation of brain circuits by designed neuro-glia interactions

Sangkyu Lee, Ph.D.

November 25(Thu) - November 25(Thu), 2021

ZOOM (ID: 728-142-6028)

Neuro@noon Seminar

Date:  12PM, Thursday, November 18th

Title: Structural modulation of brain circuits by designed neuro-glia interactions

Abstract:

The brain is made up of incredibly complex networks where many different cells are interconnected and communicate to control various brain functions including cognition, emotion, and movement. Although remarkable technical advances have been made to control the functional activity of neural circuits, methods to regulate the physical connections between brain cells are still lacking. In this talk, I will talk about the development of synthetic approaches for the structural modulation of brain circuits to directly investigate the structure-function relationships of brain networks. We designed synthetic ligands and receptors to induce direct cell-to-cell interactions. Interestingly, we found that synthetic cell-cell interactions induced by high-affinity pairs of ligand and receptor proteins resulted in a unidirectional molecular transfer that ligand molecules were taken up by receptor-expressing cells, similar to a process called ‘trogocytosis’ (trogo-: ‘nibble’). When applied to a variety of cell types, including cancer cells, fibroblasts, astrocytes, microglia, and neurons, the designed ligand-receptor pair could successfully and efficiently induce synthetic trogocytosis, indicating a high versatility of this system. During synthetic trogocytosis, we found that not only ligand molecules but also adjacent membrane lipids, membrane-anchored proteins, and even cytosolic actin cytoskeleton can be taken up by receptor-expressing cells. For  in vivo applications, we targeted the CA3-CA1 circuit of the hippocampus where synthetic ligand and receptor were expressed in CA3 pyramidal neurons and CA1 astrocytes, respectively. Axonal fragments and endogenously expressed presynaptic molecules of CA3 neurons were dramatically taken up by CA1 astrocytes, demonstrating the efficacy of synthetic trogocytosis in the mouse brain in vivo. With further engineering and characterization, synthetic trogocytosis will be developed as a powerful means for manipulating the structure of brain circuits in space and time and will contribute to a better understanding of the physiological implications of complex but finely tuned brain networks.