<p>Neural circuit function is shaped both by the cell types that comprise the circuit and the connections between them<sup><CitationRef CitationID="CR1">1</CitationRef></sup>. Neural cell types have previously been defined by morphology<sup><CitationRef CitationID="CR2">2</CitationRef>,<CitationRef CitationID="CR3">3</CitationRef></sup>, electrophysiology<sup><CitationRef CitationID="CR4">4</CitationRef></sup>, transcriptomic expression<sup><CitationRef CitationID="CR5">5</CitationRef>,<CitationRef CitationID="CR6">6</CitationRef></sup>, connectivity<sup><CitationRef AdditionalCitationIDS="CR8" CitationID="CR7">7</CitationRef>–<CitationRef CitationID="CR9">9</CitationRef></sup> or a combination of such modalities<sup><CitationRef AdditionalCitationIDS="CR11" CitationID="CR10">10</CitationRef>–<CitationRef CitationID="CR12">12</CitationRef></sup>. The Patch-seq technique enables the characterization of morphology, electrophysiology and transcriptomic properties from individual cells<sup><CitationRef AdditionalCitationIDS="CR14" CitationID="CR13">13</CitationRef>–<CitationRef CitationID="CR15">15</CitationRef></sup>. These properties were integrated to define 28 inhibitory, morpho-electric-transcriptomic (MET) cell types in mouse visual cortex<sup><CitationRef CitationID="CR16">16</CitationRef></sup>, which do not include synaptic connectivity. Conversely, large-scale electron microscopy (EM) enables morphological reconstruction and a near-complete description of a neuron’s local synaptic connectivity, but does not include transcriptomic or electrophysiological information. Here, we leveraged morphological information from Patch-seq to predict the transcriptomically defined cell subclass and/or MET-type of inhibitory neurons within a large-scale EM dataset. We further analysed Martinotti cells—a somatostatin (<i>Sst</i>)-positive<sup><CitationRef CitationID="CR17">17</CitationRef></sup> morphological cell type<sup><CitationRef CitationID="CR18">18</CitationRef>,<CitationRef CitationID="CR19">19</CitationRef></sup>—which were classified successfully into <i>Sst</i> MET-types with distinct axon myelination and synaptic output connectivity patterns. We demonstrate that morphological features can be used to link cell types across experimental modalities, enabling further comparison of connectivity to gene expression and electrophysiology. We observe unique connectivity rules for predicted <i>Sst</i> cell types.</p>

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Connectomics of predicted Sst transcriptomic types in mouse visual cortex

  • Clare R. Gamlin,
  • Casey M. Schneider-Mizell,
  • Matthew Mallory,
  • Leila Elabbady,
  • Nathan Gouwens,
  • Grace Williams,
  • Alice Mukora,
  • Rachel Dalley,
  • Agnes L. Bodor,
  • Derrick Brittain,
  • JoAnn Buchanan,
  • Daniel J. Bumbarger,
  • Emily Joyce,
  • Daniel Kapner,
  • Sam Kinn,
  • Gayathri Mahalingam,
  • Sharmishtaa Seshamani,
  • Marc Takeno,
  • Russel Torres,
  • Wenjing Yin,
  • Philip R. Nicovich,
  • J. Alexander Bae,
  • Manuel A. Castro,
  • Sven Dorkenwald,
  • Akhilesh Halageri,
  • Zhen Jia,
  • Chris Jordan,
  • Nico Kemnitz,
  • Kisuk Lee,
  • Kai Li,
  • Ran Lu,
  • Thomas Macrina,
  • Eric Mitchell,
  • Shanka Subhra Mondal,
  • Shang Mu,
  • Barak Nehoran,
  • Sergiy Popovych,
  • William Silversmith,
  • Nicholas L. Turner,
  • William Wong,
  • Jingpeng Wu,
  • Szi-chieh Yu,
  • Jim Berg,
  • Tim Jarsky,
  • Brian Lee,
  • H. Sebastian Seung,
  • Hongkui Zeng,
  • R. Clay Reid,
  • Forrest Collman,
  • Nuno Maçarico da Costa,
  • Staci A. Sorensen

摘要

Neural circuit function is shaped both by the cell types that comprise the circuit and the connections between them1. Neural cell types have previously been defined by morphology2,3, electrophysiology4, transcriptomic expression5,6, connectivity79 or a combination of such modalities1012. The Patch-seq technique enables the characterization of morphology, electrophysiology and transcriptomic properties from individual cells1315. These properties were integrated to define 28 inhibitory, morpho-electric-transcriptomic (MET) cell types in mouse visual cortex16, which do not include synaptic connectivity. Conversely, large-scale electron microscopy (EM) enables morphological reconstruction and a near-complete description of a neuron’s local synaptic connectivity, but does not include transcriptomic or electrophysiological information. Here, we leveraged morphological information from Patch-seq to predict the transcriptomically defined cell subclass and/or MET-type of inhibitory neurons within a large-scale EM dataset. We further analysed Martinotti cells—a somatostatin (Sst)-positive17 morphological cell type18,19—which were classified successfully into Sst MET-types with distinct axon myelination and synaptic output connectivity patterns. We demonstrate that morphological features can be used to link cell types across experimental modalities, enabling further comparison of connectivity to gene expression and electrophysiology. We observe unique connectivity rules for predicted Sst cell types.