Circuit organization of the excitatory sensorimotor loop through hand/forelimb S1 and M1.

Naoki Yamawaki,Gordon Mg Shepherd,Martinna G Raineri Tapies,Austin Stults,Gregory A Smith

doi:10.7554/elife.66836

Abstract

Sensory-guided limb control relies on communication across sensorimotor loops. For active touch with the hand, the longest loop is the transcortical continuation of ascending pathways, particularly the lemnisco-cortical and corticocortical pathways carrying tactile signals via the cuneate nucleus, ventral posterior lateral (VPL) thalamus, and primary somatosensory (S1) and motor (M1) cortices to reach corticospinal neurons and influence descending activity. We characterized excitatory connectivity along this pathway in the mouse. In the lemnisco-cortical leg, disynaptic cuneate→VPL→S1 connections excited mainly layer (L) 4 neurons. In the corticocortical leg, S1→M1 connections from L2/3 and L5A neurons mainly excited downstream L2/3 neurons, which excite corticospinal neurons. The findings provide a detailed new wiring diagram for the hand/forelimb-related transcortical circuit, delineating a basic but complex set of cell-type-specific feedforward excitatory connections that selectively and extensively engage diverse intratelencephalic projection neurons, thereby polysynaptically linking subcortical somatosensory input to cortical motor output to spinal cord.

Highlights

Functions of the hand and forelimb depend on sensorimotor circuits spanning multiple levels of the central nervous system (Kleinfeld et al, 2006; Arber and Costa, 2018)
We targeted those projecting to cervical level 6 (C6) in particular, as C6 is prominently involved in sensorimotor functions of the hand
We developed a paradigm for this based on associated viruses (AAV)-hSyn-Cre for anterograde transneuronal labeling (Zingg et al, 2017) to express ChR2 in the cuneo-recipient subset of ventral posterior lateral (VPL) neurons (CuN-recVPL), together with retrograde tracer injections into either the forelimb M1 or the C6 spinal cord to label projection neurons in S1 (Figure 4A)

Summary

Introduction

Functions of the hand and forelimb depend on sensorimotor circuits spanning multiple levels of the central nervous system (Kleinfeld et al, 2006; Arber and Costa, 2018). The major nodes sequentially traversed in this transcortical pathway include the cuneate nucleus, ventral posterior lateral (VPL) nucleus of thalamus, the hand/forelimb-related primary somatosensory (S1) and motor (M1) cortices. The cellular-level synaptic connectivity linking the major nodes, whereby peripheral inputs are conveyed to corticospinal neurons in S1 and/or M1, remains largely uncharacterized for these hand-related circuits. Elucidation of this circuit organization will be an important step toward characterizing basic mechanisms underlying somatosensory-guided control of the hand and forelimb and related aspects of sensorimotor integration in motor cortex (Hatsopoulos and Suminski, 2011), and can potentially inform translational approaches to restore hand function in neurological conditions (Edwards et al, 2019)

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Conclusion