Shared and distinct transcriptomic cell types across neocortical areas

Abstract

18Neocortex contains a multitude of cell types segregated into layers and functionally distinct regions. To 19investigate the diversity of cell types across the mouse neocortex, we analyzed 12,714 cells from the 20 primary visual cortex (VISp), and 9,035 cells from the anterior lateral motor cortex (ALM) by deep single-21cell RNA-sequencing (scRNA-seq), identifying 116 transcriptomic cell types. These two regions represent 22 distant poles of the neocortex and perform distinct functions. We define 50 inhibitory transcriptomic cell 23 types, all of which are shared across both cortical regions. In contrast, 49 of 52 excitatory transcriptomic 24 types were found in either VISp or ALM, with only three present in both. By combining single cell RNA-25 seq and retrograde labeling, we demonstrate correspondence between excitatory transcriptomic types and 26 their region-specific long-range target specificity. This study establishes a combined transcriptomic and 27projectional taxonomy of cortical cell types from functionally distinct regions of the mouse cortex. 28 29 1

Whole cell patch clamp analysis of non-synaptic and synaptic signaling in rodent and human supragranular neocortex

“…The recent advent of high-throughput transcriptomic single cell profiling has enabled neuroscientist to classify neocortical neurons in a robust, scalable and unbiased way. (Tasic et al, 2016;Tasic et al, 2017;Zeisel et al, 2015). Although these results are still nascent, they are in line with earlier studies that report correlating electrophysiological, anatomical and molecular cell types (Gupta, Wang, and Markram, 2000;Kawaguchi, 1993;Kawaguchi and Kubota, 1996;Kawaguchi and Kubota, 1997;Kepecs and Fishell, 2014).…”

“…The pyramidal cells and other glutamatergic neuron types comprise the majority of the neocortical neurons, approximately 80-90%, (Tremblay, Lee, and Rudy, 2016). There are multiple subtypes of cortical pyramidal cells differing in their morphology, gene expression and projection profile (Spruston, 2008;Tasic et al, 2017). The pyramidal cell subtypes are arranged in layers giving the neocortex its typical laminar architecture.…”

“…Despite their relative scarcity, these interneurons display extremely diverse morphological, electrophysiological and molecular properties and, therefore, it was always tempting for neuroscientist to classify them on the basis of these characteristics (Cauli et al, 1997;DeFelipe, 1993;Gupta, Wang, and Markram, 2000;Kawaguchi and Kubota, 1997;Kepecs and Fishell, 2014;Tasic et al, 2016;Tasic et al, 2017). The recent advent of high-throughput transcriptomic single cell profiling has enabled neuroscientist to classify neocortical neurons in a robust, scalable and unbiased way.…”

“…Axon terminals initiating from these neurons surround the somata of large Purkinje cells, creating "basket-like structures" around their cell bodies. Hence, GABAergic interneurons in all brain regions that form a high fraction of axo-somatic synapses have, therefore, traditionally been classified as basket cells (Freund and Katona, 2007;Hendry and Jones, 1985;Kisvárday, Beaulieu, and Eysel, 1993;Somogyi et al, 1983) and thus basket cells are a heterogeneous population (Tasic et al, 2016;Tasic et al, 2017).…”

“…On the other hand axo-axonic cell comprise a unique and homogeneous class of cortical interneurons (Somogyi et al, 1998;Tasic et al, 2016;Tasic et al, 2017).…”