The connectome from the cerebral cortex to skeletal muscle using viral transneuronal tracers: a review

Abstract

Connectomics has developed from an initial observation under an electron microscope to the present well-known medical imaging research approach. The emergence of the most popular transneuronal tracers has further advanced connectomics research. Researchers use the virus trans-nerve tracing method to trace the whole brain, mark the brain nerve circuit and nerve connection structure, and construct a complete nerve conduction pathway. This review assesses current methods of studying cortical to muscle connections using viral neuronal tracers and demonstrates their application in disease diagnosis and prognosis.

Keywords: Connectomics; cerebral cortex; skeletal muscle; transneuronal tracers.

Figure 1

Timeline for the development of neurotropic viruses that are currently frequently used for neural loop tracing. These are herpes simplex virus, pseudorabies virus, rabies virus, adeno-associated virus, and vesicular stomatitis virus.

Figure 2

Schematic drawing of the peripheral autonomic innervation of the skeletal muscle. PRV injected into the flexor muscles of fingers, lumbar muscles, and gastrocnemius muscles was transported to the sympathetic ganglia (SG) (by the sympathetic pathway) and the ventral horn of the spinal cord (by the motor pathway), whereas PRV injected into the masseter muscles was transported to the trigeminal ganglia (TG) by the sympathetic pathway and the motor pathway.

Figure 3

Schematic drawing of the connectivity from the masticatory muscles to the cerebral cortex. When the virus is injected into the masticatory muscles, it is transported in the retrograde direction to infect the trigeminal ganglia (TG) (i.e., first-order neurons) that innervate the masticatory muscles. Then the virus is transported transneuronally in the retrograde direction to label the trigeminal subnucleus caudalis (Vc) (i.e., second-order neurons) that synapse onto the infected TG neurons. NTS, nucleus of the solitary tract; RVLM, rostral ventrolateral medulla. Schematic illustration of the orofacial and trigeminal nervous system came from Kim YS et al. Central terminal sensitization of TRPV1 by descending serotonergic facilitation modulates chronic pain. Neuron. 2014;81:873-887.

Figure 4

Schematic drawing of the connectivity from the gastrocnemius muscles to the cerebral cortex. When the PRV virus is injected into the gastrocnemius muscles, it is transported in the retrograde direction to infect the dorsal root ganglia (DRG) (i.e., first-order neurons) that innervate the gastrocnemius muscles. Then the virus is transported transneuronally in the retrograde direction to label spinal cord ventral horn and sympathetic preganglionic neurons (SPNs) (i.e., second-order neurons) that synapse onto the infected DRG neurons. DRG, dorsal root ganglia; Ins, interneurons; SPNs, sympathetic preganglionic neurons.