MDGA1 negatively regulates amyloid precursor protein–mediated synapse inhibition in the hippocampus

Abstract

Significance This study demonstrates a universal synaptic mechanism responsible for tuning GABAergic neural circuit strength and turnover. These observations are relevant to the issue of neural circuit dynamics, which have only been investigated in certain limited contexts, particularly at a subset of glutamatergic neural circuits. Our work provides compelling evidence to support a crucial and unique physiological role for amyloid precursor protein (APP) in shaping GABAergic neural circuits. Our unequivocal demonstration of the physiological significance of MDGA1–APP complexes at specific hippocampal GABAergic neural circuits enables us to propose a conceptual framework that adds a striking twist to our understanding of the organization of mammalian inhibitory synapses in addition to unmasking a previously unidentified physiological role for APP proteins.