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

doi:10.1016/j.celrep.2024.114112

Focal clusters of peri-synaptic matrix contribute to activity-dependent plasticity and memory in mice

Cell Rep. 2024 Apr 25;43(5):114112. doi: 10.1016/j.celrep.2024.114112. Online ahead of print.

Authors

Gabriele Chelini¹, Hadi Mirzapourdelavar², Peter Durning³, David Baidoe-Ansah², Manveen K Sethi⁴, Sinead M O'Donovan⁵, Torsten Klengel⁶, Luigi Balasco⁷, Cristina Berciu³, Anne Boyer-Boiteau³, Robert McCullumsmith⁵, Kerry J Ressler⁸, Joseph Zaia⁹, Yuri Bozzi¹⁰, Alexander Dityatev¹¹, Sabina Berretta¹²

Affiliations

¹ 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.
² Molecular Neuroplasticity Group, German Center for Neurodegenerative Diseases, Magdeburg 39120 Saxony-Anhalt, Germany.
³ Translational Neuroscience Laboratory, McLean Hospital, Belmont, MA 02478, USA.
⁴ Center for Biomedical Mass Spectrometry, Department of Biochemistry and Cell Biology, Boston University School of Medicine, Boston, MA 02118, USA.
⁵ Cognitive Disorders Research Laboratory, University of Toledo, Toledo, OH 43606, USA.
⁶ 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.
⁷ Center for Mind/Brain Sciences, University of Trento, Rovereto 38068 Trento, Italy.
⁸ 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.
⁹ 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.
¹⁰ Center for Mind/Brain Sciences, University of Trento, Rovereto 38068 Trento, Italy; CNR Neuroscience Institute Pisa, 56124 Pisa, Italy.
¹¹ 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.
¹² 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. Electronic address: s.berretta@mclean.harvard.edu.

PMID: 38676925
DOI: 10.1016/j.celrep.2024.114112

Abstract

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.

Keywords: CP: Cell biology; CP: Neuroscience; CS clusters; chondrotin sulfate proteoglycans; extracellular matrix; hippocampus; immunoprecipitation; learning and memory; sensory manipulation; synaptic plasticity; versican.