Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory in mice
Gabriele Chelini,
Hadi Mirzapourdelavar,
Peter Durning,
David Baidoe-Ansah,
Manveen K. Sethi,
Sinead M. O’Donovan,
Torsten Klengel,
Luigi Balasco,
Cristina Berciu,
Anne Boyer-Boiteau,
Robert McCullumsmith,
Kerry J. Ressler,
Joseph Zaia,
Yuri Bozzi,
Alexander Dityatev,
Sabina Berretta
Affiliations
Gabriele Chelini
Translational Neuroscience Laboratory, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA; Center for Mind/Brain Sciences, University of Trento, Rovereto 38068 Trento, Italy
Hadi Mirzapourdelavar
Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases, Magdeburg 39120 Saxony-Anhalt, Germany
Peter Durning
Translational Neuroscience Laboratory, McLean Hospital, Belmont, MA 02478, USA
David Baidoe-Ansah
Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases, Magdeburg 39120 Saxony-Anhalt, Germany
Manveen K. Sethi
Center for Biomedical Mass Spectrometry, Department of Biochemistry and Cell Biology, Boston University School of Medicine, Boston, MA 02118, USA
Sinead M. O’Donovan
Cognitive Disorders Research Laboratory, University of Toledo, Toledo, OH 43606, USA
Torsten Klengel
Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA; Translational Molecular Genomics Laboratory, Mclean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, University Medical Center Göttingen, 37075 Göttingen, Germany
Luigi Balasco
Center for Mind/Brain Sciences, University of Trento, Rovereto 38068 Trento, Italy
Cristina Berciu
Translational Neuroscience Laboratory, McLean Hospital, Belmont, MA 02478, USA
Anne Boyer-Boiteau
Translational Neuroscience Laboratory, McLean Hospital, Belmont, MA 02478, USA
Robert McCullumsmith
Cognitive Disorders Research Laboratory, University of Toledo, Toledo, OH 43606, USA
Kerry J. Ressler
Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02215, USA; Neurobiology of Fear Laboratory, McLean Hospital, Belmont, MA 02478, USA
Joseph Zaia
Center for Biomedical Mass Spectrometry, Department of Biochemistry and Cell Biology, Boston University School of Medicine, Boston, MA 02118, USA; Bioinformatics Program, Boston University, Boston, MA 02215, USA
Yuri Bozzi
Center for Mind/Brain Sciences, University of Trento, Rovereto 38068 Trento, Italy; CNR Neuroscience Institute Pisa, 56124 Pisa, Italy
Alexander Dityatev
Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases, Magdeburg 39120 Saxony-Anhalt, Germany; Medical Faculty, Otto von Guericke University, Magdeburg 39106 Saxony-Anhalt, Germany; Center for Behavioral Brain Sciences, Otto von Guericke University, Magdeburg 39106 Saxony-Anhalt, Germany
Sabina Berretta
Translational Neuroscience Laboratory, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA; Program in Neuroscience, Harvard Medical School, Boston, MA 02215, USA; Corresponding author
Summary: Recent findings show that effective integration of novel information in the brain requires coordinated processes of homo- and heterosynaptic plasticity. In this work, we hypothesize that activity-dependent remodeling of the peri-synaptic extracellular matrix (ECM) contributes to these processes. We show that clusters of the peri-synaptic ECM, recognized by CS56 antibody, emerge in response to sensory stimuli, showing temporal and spatial coincidence with dendritic spine plasticity. Using CS56 co-immunoprecipitation of synaptosomal proteins, we identify several molecules involved in Ca2+ signaling, vesicle cycling, and AMPA-receptor exocytosis, thus suggesting a role in long-term potentiation (LTP). Finally, we show that, in the CA1 hippocampal region, the attenuation of CS56 glycoepitopes, through the depletion of versican as one of its main carriers, impairs LTP and object location memory in mice. These findings show that activity-dependent remodeling of the peri-synaptic ECM regulates the induction and consolidation of LTP, contributing to hippocampal-dependent memory.
