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Introduction
  • Synapses are the specialized junctions between nerve cells and play a fundamental role in the organization of brain circuits and behaviour. A hallmark of synapses is their complexity in numbers and molecular composition.
  • The synaptome is the complement or catalog of synapse types and synaptome maps describes the anatomical distribution of synapse types in the brain.
  • We have developed a method to analyze and map the molecular composition of individual synapses and characterized synaptome maps of the whole mouse brain.
  • The tables and the source code refered in the paper can be downloaded from here
Synaptome mapping pipeline
  • The Genes to Cognition Synaptome Mapping (G2CSynMaP) pipeline consisted of four main components: A) fluorescent labelling of synaptic proteins using genome engineering, B) single-synapse resolution imaging across entire brain sections, C) data analysis, D) data storage and dissemination.
  • Synapses were imaged in five coronal sections covering 13 overarching brain areas: Isocortex, Olfactory areas (OLF), Hippocampal formation (HPF), Cortical Subplate (CTXsp), Striatum (STR), Pallidum (PAL), Thalamus (TH), Hypothalamus (HY), Midbrain (MB), Pons (P), Medulla (MY), Cerebellum (CB) and Fiber Tracts (FT).
  • The spatial distribution of synapse molecules and synapse types is displayed as either a ‘supervised’ image of regions registered to the coordinates of the Allen Reference Atlas. or as an ‘unsupervised’ image of voxels.
Molecular labelling of postsynaptic proteins.
  • We focused on two excitatory synapse postsynaptic proteins, PSD95 and SAP102, because they are scaffold proteins that assemble different multiprotein complexes, control synaptic plasticity and behaviour. Each protein is mutated in brain diseases that cause cognitive disorders.
  • The endogenous PSD95 molecule was labelled with enhanced green fluorescent protein (eGFP) and SAP102 was labelled with monomeric Kusabira Orange 2 (mKO2).
  • Differential labelling generates a catalog of 3 synapse subtypes and 37 subtypes: Type 1 synapses express only PSD95 (11 subtypes), Type 2 express only SAP102 (7 subtypes) and Type 3 (19 subtypes) express a combination of the two proteins.
Visualization of synaptome maps
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Article

Synaptome maps of the mouse brain are reprogrammed by disease mutations.

Fei Zhu

Equal Contribution Genes to Cognition program, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK

Mélissa Cizeron

Equal Contribution Genes to Cognition program, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK

Zhen Qiu

Equal Contribution Genes to Cognition program, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK

Ruth Benavides-Piccione,

Instituto Cajal (CSIC) and Centro de Tecnología Biomédica (UPM), Madrid, Spain.

Maksym V. Kopanitsa

Synome Ltd, Babraham Research Campus, Cambridge CB22 3AT, UK

Nathan Skene

Genes to Cognition program, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK

Javier DeFelipe

Instituto Cajal (CSIC) and Centro de Tecnología Biomédica (UPM), Madrid, Spain.

Erik Fransén,

Department of Computational Science and Technology, School of Computer Science and Communication, KTH Royal Institute of Technology, SE-10044 Stockholm, Sweden

Noboru H. Komiyama

Genes to Cognition program, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK

Seth G. N. Grant

Corresponding author
Genes to Cognition program, Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh EH16 4SB, UK

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