4.7 Review

Progress towards a cellularly resolved mouse mesoconnectome is empowered by data fusion and new neuroanatomy techniques

Journal

NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
Volume 128, Issue -, Pages 569-591

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neubiorev.2021.06.016

Keywords

Neuroanatomy review; Data fusion; Computational framework; Cell-type specificity; Mouse mesoconnectome; Shared factorisation; Multi-modal clustering; Probabilistic inference; Spatial registration; Spatial transcriptomics and proteomics; Connectomics; Tract-tracing; In situ hybridization; Single-cell RNA sequencing; Morphological reconstructions; Barcode sequencing; Light-sheet microscopy; Diffusion tensor imaging

Funding

  1. European Union [785907]
  2. FLAG-ERA project FIIND [NWO054-15-104]
  3. FLAG-ERA project NeuronsReunited [NWO 680-91-318, JTC 2019]

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Advanced techniques for large-scale cellular level data related to the mouse brain connectome have rapidly improved over the past decade. However, a detailed mapping of cell-type-specific projection patterns is still lacking. This work reviews neuroanatomical and data fusion techniques within a proposed Multimodal Connectomic Integration Framework to enhance the cellularly resolved mouse mesoconnectome.
Over the past decade there has been a rapid improvement in techniques for obtaining large-scale cellular level data related to the mouse brain connectome. However, a detailed mapping of cell-type-specific projection patterns is lacking, which would, for instance, allow us to study the role of circuit motifs in cognitive processes. In this work, we review advanced neuroanatomical and data fusion techniques within the context of a proposed Multimodal Connectomic Integration Framework for augmenting the cellularly resolved mouse mesoconnectome. First, we emphasize the importance of registering data modalities to a common reference atlas. We then review a number of novel experimental techniques that can provide data for characterizing cell-types in the mouse brain. Furthermore, we examine a number of data integration strategies, which involve fine-grained cell-type classification, spatial inference of cell densities, latent variable models for the mesoconnectome and multi-modal factorisation. Finally, we discuss a number of use cases which depend on connectome augmentation techniques, such as model simulations of functional connectivity and generating mechanistic hypotheses for animal disease models.

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