Distinct but overlapping roles of LRRTM1 and LRRTM2 in developing and mature hippocampal circuits
Shreya H Dhume,
Steven A Connor,
Fergil Mills,
Parisa Karimi Tari,
Sarah HM Au-Yeung,
Benjamin Karimi,
Shinichiro Oku,
Reiko T Roppongi,
Hiroshi Kawabe,
Shernaz X Bamji,
Yu Tian Wang,
Nils Brose,
Michael F Jackson,
Ann Marie Craig,
Tabrez J Siddiqui
Affiliations
Shreya H Dhume
Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada
Steven A Connor
Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Biology, York University, Toronto, Canada
Fergil Mills
Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, Canada
Parisa Karimi Tari
Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Biology, York University, Toronto, Canada
Sarah HM Au-Yeung
Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
Benjamin Karimi
Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada
Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada; Department of Psychiatry and Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada
Reiko T Roppongi
Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada
Department of Molecular Neurobiology, Max Planck Institute for Multidisciplinary Sciences, Göttingen, Germany; Division of Pathogenetic Signaling, Department of Biochemistry and Molecular Biology, Kobe University Graduate School of Medicine, Kobe, Japan; Department of Gerontology, Laboratory of Molecular Life Science, Institute of Biomedical Research and Innovation, Foundation for Biomedical Research and Innovation at Kobe, Kobe, Japan; Department of Pharmacology, Gunma University Graduate School of Medicine, Gunma, Japan
Neuroscience Research Program, Kleysen Institute for Advanced Medicine, Health Sciences Centre, Winnipeg, Canada; Department of Physiology and Pathophysiology, University of Manitoba, Winnipeg, Canada; The Children's Hospital Research Institute of Manitoba, Winnipeg, Canada; Program in Biomedical Engineering, University of Manitoba, Winnipeg, Canada
LRRTMs are postsynaptic cell adhesion proteins that have region-restricted expression in the brain. To determine their role in the molecular organization of synapses in vivo, we studied synapse development and plasticity in hippocampal neuronal circuits in mice lacking both Lrrtm1 and Lrrtm2. We found that LRRTM1 and LRRTM2 regulate the density and morphological integrity of excitatory synapses on CA1 pyramidal neurons in the developing brain but are not essential for these roles in the mature circuit. Further, they are required for long-term-potentiation in the CA3-CA1 pathway and the dentate gyrus, and for enduring fear memory in both the developing and mature brain. Our data show that LRRTM1 and LRRTM2 regulate synapse development and function in a cell-type and developmental-stage-specific manner, and thereby contribute to the fine-tuning of hippocampal circuit connectivity and plasticity.
