Localization and Functional Characterization of MDGA1 in Mouse Hippocampus

Abstract

Neuron-to-neuron communication occurs mainly at chemical synapses. A network of synaptic organizer molecules orchestrates synapse formation, remodeling, and plasticity. The GPI-anchored MAM domain-containing glycosylphosphatidylinositol anchor protein 1 (MDGA1) has been proposed to act as a repressor of synapse formation, a role played by very few other cell adhesion molecules. In humans, mutations in MDGA1 are associated with schizophrenia, bipolar disorder, and depression. MDGA1 knock-out mice show memory deficits and altered synaptic excitation/inhibition balance. Despite significant interest in this protein in the past decade, MDGA1’s precise localization and function in vivo are still unclear. Here, we defined the localization of MDGA1 using epitope-tagged MDGA1 knock-in male and female mice. We found that MDGA1 expression peaks in forebrain during the first postnatal weeks. In hippocampal field CA1, MDGA1 localizes to dendrites but shows no clear enrichment at excitatory or inhibitory synapses. Slice electrophysiology showed that neither pre- nor postsynaptic acute MDGA1 deletion affect inhibitory or excitatory synaptic transmission. Altogether, our findings indicate that MDGA1 may transiently inhabit, but is not a strong regulator of, hippocampal synapses in young mice.