LRRTM3 regulates activity-dependent synchronization of synapse properties in topographically connected hippocampal neural circuits
Jinhu Kim, Dongseok Park, Na‐Young Seo, Taek-Han Yoon, Gyu Hyun Kim, Sang-Hoon Lee, Jinsoo Seo, Ji Won Um, Kea Joo Lee, Jaewon Ko
Abstract
Significance The present study utilized imaging, electrophysiology, and three-dimensional high-resolution electron microscopy analyses to address the neural circuit role of LRRTM3 in vivo, using both conventional and conditional Lrrtm3 -KO mice. We found that LRRTM3 is required for the specific assembly and function of the medial perforant path to dentate gyrus synapses. Moreover, LRRTM3 is required for proper excitatory synaptic connectivity and long-term synaptic plasticity at mossy fiber–CA3 synapses. Strikingly, presynaptic inactivation of medial perforant path–dentate gyrus (MPP–DG) circuit activities completely rescued the impaired excitatory synaptic inputs and long-term synaptic plasticity of Lrrtm3 -KO mice, demonstrating that LRRTM3 is involved in activity-dependent hippocampal excitatory synapse refinement/stabilization, which is dictated and synchronized by glutamatergic neurotransmission.