A repeated molecular architecture across thalamic pathways

Abstract

Thalamus is the central communication hub of the forebrain, providing cerebral cortex with inputs from sensory organs, subcortical systems, and cortex itself. Multiple thalamic regions send convergent information to each cortical region, but the organizational logic of thalamic projections has remained elusive. Through comprehensive transcriptional analyses of retrogradely labeled thalamic neurons in adult mice, we identify three major profiles of thalamic pathway. These profiles exist along a continuum that is repeated across all major projection systems, such as those for vision, motor control, and cognition. The largest component of gene expression variation in mouse thalamus is topographically organized with features conserved in humans. Transcriptional differences between these thalamic neuronal identities are tied to cellular features critical for function, such as axonal morphology and membrane properties. Molecular profiling therefore reveals covariation in properties of thalamic pathways serving all major input modalities and output targets, establishing a molecular framework for understanding thalamus. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Activity labeling in vivo using CaMPARI2 reveals electrophysiological differences between neurons with high and low firing rate set points

“…Recently, there has been a strong push to catalog and sort all of the neurons in various brain regions, or even the entire brain Gouwens et al, 2019;Phillips et al, 2019;Saunders et al, 2018;Sugino et al, 2019;Tasic et al, 2018;Zeisel et al, 2018Zeisel et al, , 2015, using various approaches to separate cells into classes. Most popular have been techniques that sort cells based on their transcriptional profile or projection targets, though efforts are ongoing to incorporate this anatomical and transcriptional data with electrophysiological data (Gouwens et al, 2019).…”

Core and Matrix Thalamic Sub-Populations Relate to Spatio-Temporal Cortical Connectivity Gradients

“…Whereas individual thalamic nuclei contain a blend of both cell-types, some nuclei are almost exclusively of the 'Matrix' type (these are known as 'intralaminar' nuclei; (Van der Werf et al, 2002). Of note, other schemes have been devised to parse the thalamus (Phillips et al, 2019), including the class of cortical region proposed to 'drive' activity in the glutamatergic relay nuclei (Sherman, 2007). However, these proposals are not considered in detail here.…”

Whole-body integration of gene expression and single-cell morphology

“…Several recent studies have succeeded to make this link for restricted sets of cells. For example, retrograde labelling of neurons prior to sequencing allows integration of partial projection information with transcriptomics Phillips et al, 2019;Tasic et al, 2018). Similarly, photoconversion of dyes in selected cells can be used as a method to correlate single-cell sequencing with live imaging techniques (Lee et al, 2019;Pfeffer and Beltramo, 2017).…”

“…Other techniques based on probe hybridisation or local sequencing provide expression information in situ, recovering the position of the cells interrogated (reviewed in (Lein et al, 2017)). Such spatial transcriptomics techniques can be correlated and complemented with single-cell transcriptomics Phillips et al, 2019;Qian et al, 2020), and recent developments using viral barcoding have also enabled the integration of long-range projection information in a brain-wide manner (Chen et al, 2019). However, these approaches only retrieve multimodal information for small subsets of cells and/or their scalability is not straight-forward beyond a set of tissue slices (Ortiz et al, 2019), though this could suffice for small organisms (Ebbing et al, 2018).…”