NGL-1/LRRC4C Deletion Moderately Suppresses Hippocampal Excitatory Synapse Development and Function in an Input-Independent Manner

• Published in: Frontiers in molecular neuroscience Vol. 12; p. 119
• Main Authors: Choi, Yeonsoo, Park, Haram, Jung, Hwajin, Kweon, Hanseul, Kim, Seoyeong, Lee, Soo Yeon, Han, Hyemin, Cho, Yisul, Kim, Seyeon, Sim, Woong Seob, Kim, Jeongmin, Bae, Yongchul, Kim, Eunjoon
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Research Foundation 14.05.2019; Frontiers Media S.A
• Subjects: Brain research; Dendritic spines; Functional plasticity; Hippocampus; LRRC4C; Microscopy; Neurons; Neuroscience; Neurosciences; NGL-1; Phosphatase; Postsynaptic density proteins; Potassium; Proteins; PSD-95; Stratum radiatum; synapse; Synaptic plasticity; synaptic transmission; trans-synaptic adhesion; Trends; South Korea; trans-synaptic adhesion; synaptic transmission; NGL-1; synapse; synaptic plasticity; LRRC4C; PSD-95
• ISSN: 1662-5099; 1662-5099
• DOI: 10.3389/fnmol.2019.00119

Netrin-G ligand-1 (NGL-1), also known as LRRC4C, is a postsynaptic densities (PSDs)-95-interacting postsynaptic adhesion molecule that interacts trans-synaptically with presynaptic netrin-G1. NGL-1 and its family member protein NGL-2 are thought to promote excitatory synapse development through largely non-overlapping neuronal pathways. While NGL-2 is critical for excitatory synapse development in specific dendritic segments of neurons in an input-specific manner, whether NGL-1 has similar functions is unclear. Here, we show that deletion in male mice moderately suppresses excitatory synapse development and function, but surprisingly, does so in an input-independent manner. While NGL-1 is mainly detected in the stratum lacunosum moleculare (SLM) layer of the hippocampus relative to the stratum radiatum (SR) layer, NGL-1 deletion leads to decreases in the number of PSDs in both SLM and SR layers in the ventral hippocampus. In addition, both SLM and SR excitatory synapses display suppressed short-term synaptic plasticity in the ventral hippocampus. These morphological and functional changes are either absent or modest in the dorsal hippocampus. The input-independent synaptic changes induced by deletion involve abnormal translocation of NGL-2 from the SR to SLM layer. These results suggest that deletion moderately suppresses hippocampal excitatory synapse development and function in an input-independent manner.