Translating single-neuron axonal reconstructions into meso-scale connectivity statistics in the mouse somatosensory thalamus

Abstract

Characterizing the connectomic and morphological diversity of thalamic neurons is key for better understanding how the thalamus relays sensory inputs to the cortex. The recent public release of complete single-neuron morphological reconstructions enables the analysis of previously inaccessible connectivity patterns from individual neurons. Here we focus on the Ventral Posteromedial (VPM) nucleus and characterize the full diversity of 257 VPM neurons, obtained by combining data from the MouseLight and Braintell projects. Neurons were clustered according to their most dominantly targeted cortical area and further subdivided by their jointly targeted areas. We obtained a 2D embedding of morphological diversity using the dissimilarity between all pairs of axonal trees. The curved shape of the embedding allowed us to characterize neurons by a 1-dimensional coordinate. The coordinate values were aligned both with the progression of soma position along the dorsal-ventral and lateral-medial axes and with that of axonal terminals along the posterior-anterior and medial-lateral axes, as well as with an increase in the number of branching points, distance from soma and branching width. Taken together, we have developed a novel workflow for linking three challenging aspects of connectomics, namely the topography, higher order connectivity patterns and morphological diversity, with VPM as a test-case. The workflow is linked to a unified access portal that contains the morphologies and integrated with 2D cortical flatmap and subcortical visualization tools. The workflow and resulting processed data have been made available in Python, and can thus be used for modeling and experimentally validating new hypotheses on thalamocortical connectivity.