Single-Nucleus RNA Sequencing of Developing and Mature Superior Colliculus Identifies Neuronal Diversity and Candidate Mediators of Circuit Assembly

The superior colliculus (SC) is a sensorimotor structure in the midbrain that integrates input from multiple sensory modalities to initiate motor commands. It undergoes well-characterized steps of circuit assembly during development, rendering the mouse SC a popular model to study establishment and refinement of neural connectivity. Here we performed single nucleus RNA-sequencing analysis of the mouse SC isolated at various developmental time points. Our study provides a transcriptomic landscape of the cell types that comprise the SC across murine development with particular emphasis on neuronal heterogeneity. We used these data to identify Pax7 as a marker for an anatomically homogeneous population of GABAergic neurons. Lastly, we report a repertoire of genes differentially expressed across the different postnatal ages, many of which are known to regulate axon guidance and synapse formation. Our data provide a valuable resource for interrogating the mechanisms of circuit development, and identifying markers for manipulating specific SC neuronal populations and circuits.

[1]  G. Konopka,et al.  Neuronal ambient RNA contamination causes misinterpreted and masked cell types in brain single-nuclei datasets , 2022, Neuron.

[2]  J. Rubenstein,et al.  Trans-Seq maps a selective mammalian retinotectal synapse instructed by Nephronectin , 2022, Nature Neuroscience.

[3]  E. H. Feinberg,et al.  Virally encoded connectivity transgenic overlay RNA sequencing (VECTORseq) defines projection neurons involved in sensorimotor integration , 2021, bioRxiv.

[4]  A. Saleem,et al.  Functional Organisation of the Mouse Superior Colliculus , 2021, Frontiers in Neural Circuits.

[5]  A. Huberman,et al.  Divergent outputs of the ventral lateral geniculate nucleus mediate visually evoked defensive behaviors. , 2021, Cell reports.

[6]  M. Wegner,et al.  SoxD transcription factor deficiency in Schwann cells delays myelination in the developing peripheral nervous system , 2021, Scientific Reports.

[7]  Nicholas N. Foster,et al.  Organization of the inputs and outputs of the mouse superior colliculus , 2021, Nature Communications.

[8]  Xiaoqun Wang,et al.  Transcriptomic encoding of sensorimotor transformation in the midbrain , 2021, bioRxiv.

[9]  J. Sanes,et al.  Synaptic Specificity, Recognition Molecules, and Assembly of Neural Circuits , 2020, Cell.

[10]  M. Bickford,et al.  GABAergic cell types in the superficial layers of the mouse superior colliculus , 2020, The Journal of comparative neurology.

[11]  L. Masullo,et al.  Genetically Defined Functional Modules for Spatial Orienting in the Mouse Superior Colliculus , 2019, Current Biology.

[12]  Congping Shang,et al.  A subcortical excitatory circuit for sensory-triggered predatory hunting in mice , 2019, Nature Neuroscience.

[13]  Maximilian Haeussler,et al.  Single-cell genomics identifies cell type–specific molecular changes in autism , 2019, Science.

[14]  Allon M Klein,et al.  Scrublet: Computational Identification of Cell Doublets in Single-Cell Transcriptomic Data. , 2019, Cell systems.

[15]  Samantha Riesenfeld,et al.  EmptyDrops: distinguishing cells from empty droplets in droplet-based single-cell RNA sequencing data , 2019, Genome Biology.

[16]  Zhi-Li Huang,et al.  Superior Colliculus GABAergic Neurons Are Essential for Acute Dark Induction of Wakefulness in Mice , 2019, Current Biology.

[17]  Trygve E Bakken,et al.  Single-nucleus and single-cell transcriptomes compared in matched cortical cell types , 2018, PloS one.

[18]  Lai Guan Ng,et al.  Dimensionality reduction for visualizing single-cell data using UMAP , 2018, Nature Biotechnology.

[19]  A. Butte,et al.  Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage , 2018, Nature Immunology.

[20]  Christoph Hafemeister,et al.  Comprehensive integration of single cell data , 2018, bioRxiv.

[21]  Jianhua Cang,et al.  Visual Function, Organization, and Development of the Mouse Superior Colliculus. , 2018, Annual review of vision science.

[22]  Samuel L. Wolock,et al.  Scrublet: computational identification of cell doublets in single-cell transcriptomic data , 2018, bioRxiv.

[23]  Samuel D. Gale,et al.  Distinct cell types in the superficial superior colliculus project to the dorsal lateral geniculate and lateral posterior thalamic nuclei , 2018, Journal of neurophysiology.

[24]  P. May,et al.  Parvalbumin and GABA Microcircuits in the Mouse Superior Colliculus , 2018, Front. Neural Circuits.

[25]  Paul Hoffman,et al.  Integrating single-cell transcriptomic data across different conditions, technologies, and species , 2018, Nature Biotechnology.

[26]  Jiajing Zhang,et al.  Divergent midbrain circuits orchestrate escape and freezing responses to looming stimuli in mice , 2018, Nature Communications.

[27]  Shinya Ito,et al.  The Mouse Superior Colliculus: An Emerging Model for Studying Circuit Formation and Function , 2018, Front. Neural Circuits.

[28]  Sinisa Hrvatin,et al.  Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement , 2018, Proceedings of the National Academy of Sciences.

[29]  M. A. Basso,et al.  Circuits for Action and Cognition: A View from the Superior Colliculus. , 2017, Annual review of vision science.

[30]  Hongkui Zeng,et al.  Diverse Central Projection Patterns of Retinal Ganglion Cells. , 2017, Cell reports.

[31]  J. B. Demb,et al.  Molecular features distinguish ten neuronal types in the mouse superficial superior colliculus , 2016, The Journal of comparative neurology.

[32]  K. Lesch,et al.  Cadherin-13, a risk gene for ADHD and comorbid disorders, impacts GABAergic function in hippocampus and cognition , 2015, Translational Psychiatry.

[33]  Xintian Hu,et al.  Processing of visually evoked innate fear by a non-canonical thalamic pathway , 2015, Nature Communications.

[34]  Samuel D. Gale,et al.  Distinct Representation and Distribution of Visual Information by Specific Cell Types in Mouse Superficial Superior Colliculus , 2014, The Journal of Neuroscience.

[35]  Peter Jonas,et al.  Fast-spiking, parvalbumin+ GABAergic interneurons: From cellular design to microcircuit function , 2014, Science.

[36]  G. Knott,et al.  Connexin 30 sets synaptic strength by controlling astroglial synapse invasion , 2014, Nature Neuroscience.

[37]  Y. Yanagawa,et al.  Cholinergic responses in GABAergic and non‐GABAergic neurons in the intermediate gray layer of mouse superior colliculus , 2012, The European journal of neuroscience.

[38]  Ben A. Barres,et al.  Regulation of synaptic connectivity by glia , 2010, Nature.

[39]  J. Sanes,et al.  Laminar Restriction of Retinal Ganglion Cell Dendrites and Axons: Subtype-Specific Developmental Patterns Revealed with Transgenic Markers , 2010, The Journal of Neuroscience.

[40]  Michael P Stryker,et al.  Roles of Ephrin-As and Structured Activity in the Development of Functional Maps in the Superior Colliculus , 2008, The Journal of Neuroscience.

[41]  A. Huberman,et al.  Architecture and Activity-Mediated Refinement of Axonal Projections from a Mosaic of Genetically Identified Retinal Ganglion Cells , 2008, Neuron.

[42]  P. Caroni,et al.  Characterization of BASP1‐mediated neurite outgrowth , 2008, Journal of neuroscience research.

[43]  C. Mason,et al.  Zic2 Regulates Retinal Ganglion Cell Axon Avoidance of ephrinB2 through Inducing Expression of the Guidance Receptor EphB1 , 2008, The Journal of Neuroscience.

[44]  Ian D. Thompson,et al.  Opposing Gradients of Ephrin-As and EphA7 in the Superior Colliculus Are Essential for Topographic Mapping in the Mammalian Visual System , 2005, Neuron.

[45]  M. Meredith,et al.  Chemoarchitecture of GABAergic neurons in the ferret superior colliculus , 2002, The Journal of comparative neurology.

[46]  R. Moore,et al.  Efferent projections of the intergeniculate leaflet and the ventral lateral geniculate nucleus in the rat , 2000, The Journal of comparative neurology.

[47]  V. Casagrande.  A third parallel visual pathway to primate area V1 , 1994, Trends in Neurosciences.

[48]  C. Jeon,et al.  The calcium binding proteins parvalbumin and calbindin‐D 28K form complementary patterns in the cat superior colliculus , 1992, The Journal of comparative neurology.

[49]  W. B. Spatz,et al.  Parvalbumin in rat superior colliculus , 1990, Neuroscience Letters.

[50]  E. Schon,et al.  Transthyretin , 1986, Neurology.

[51]  W M Cowan,et al.  An autoradiographic study of the efferent connections of the ventral lateral geniculate nucleus in the albino rat and the cat , 1974, The Journal of comparative neurology.

[52]  P. May.  The mammalian superior colliculus: laminar structure and connections. , 2006, Progress in brain research.

[53]  R. Mize,et al.  Neurochemical microcircuitry underlying visual and oculomotor function in the cat superior colliculus. , 1996, Progress in brain research.

[54]  R. Mize,et al.  The organization of GABAergic neurons in the mammalian superior colliculus. , 1992, Progress in brain research.

[55]  L E Mays,et al.  Signal transformations required for the generation of saccadic eye movements. , 1990, Annual review of neuroscience.