The precision of skilled forelimb movement has long been presumed to rely on rapid feedback corrections triggered by internally-directed copies of outgoing motor commands – but the functional relevance of inferred internal copy circuits has remained unclear. One class of spinal interneurons implicated in the control of mammalian forelimb movement, cervical propriospinal neurons (PNs), has the potential to convey an internal copy of pre-motor signals through dual innervation of forelimb-innervating motor neurons and pre-cerebellar neurons of the lateral reticular nucleus. We have examined whether the PN internal copy pathway functions in the control of goal-directed reaching. In mice, PNs include a genetically-accessible subpopulation of cervical V2a interneurons, and their targeted ablation perturbs reaching while leaving intact other elements of forelimb movement. Moreover, optogenetic activation of the PN internal copy branch recruits a rapid cerebellar feedback loop that modulates forelimb motor neuron activity and severely disrupts reaching kinematics. Our findings implicate V2a PNs as the focus of an internal copy pathway assigned to the rapid updating of motor output during reaching behavior.

It is generally accepted that the direct connection from the motor cortex to spinal motor neurons is responsible for dexterous hand movements in primates. However, the role of the 'phylogenetically older' indirect pathways from the motor cortex to motor neurons, mediated by spinal interneurons, remains elusive. Here we used a novel double-infection technique to interrupt the transmission through the propriospinal neurons (PNs), which act as a relay of the indirect pathway in macaque monkeys (Macaca fuscata and Macaca mulatta). The PNs were double infected by injection of a highly efficient retrograde gene-transfer vector into their target area and subsequent injection of adeno-associated viral vector at the location of cell somata. This method enabled reversible expression of green fluorescent protein (GFP)-tagged tetanus neurotoxin, thereby permitting the selective and temporal blockade of the motor cortex–PN–motor neuron pathway. This treatment impaired reach and grasp movements, revealing a critical role for the PN-mediated pathway in the control of hand dexterity. Anti-GFP immunohistochemistry visualized the cell bodies and axonal trajectories of the blocked PNs, which confirmed their anatomical connection to motor neurons. This pathway-selective and reversible technique for blocking neural transmission does not depend on cell-specific promoters or transgenic techniques, and is a new and powerful tool for functional dissection in system-level neuroscience studies.

. Dexterous finger movements in primate without monosynaptic corticomotoneuronal excitation.

From an evolutionary perspective, it is clear that basic motor functions such as locomotion and posture are largely controlled by neural circuitries residing in the spinal cord and brain-stem. The control of voluntary movements such as skillful reaching and grasping is generally considered to be governed by neural circuitries in the motor cortex that connect directly to motoneurons via the corticomotoneuronal (CM) pathway. The CM pathway may act together with several brain-stem systems that also act directly with motoneurons. This simple view was challenged by work in the cat, which lacks the direct CM system, showing that the motor commands for reaching and grasping could be mediated via spinal interneurons with input from the motor-cortex and brain-stem systems. It was further demonstrated that the spinal interneurons mediating the descending commands for reaching and grasping constitute separate and distinct populations from those involved in locomotion and posture. The aim of this review is to describe populations of spinal interneurons that are involved in the control of skilled reaching and grasping in the cat, monkey, and human.

In the rat, some findings have been taken to suggest the existence of monosynaptic corticomotoneuronal (CM) connections. Because this connection is believed to be largely responsible for the ability to make independent digit movements in primates and man, it has been inferred that the monosynaptic CM connection in the rat is likewise important for skilled prehension. Comparison of intra- and extracellular recordings from forelimb motoneurons in anesthetized rats, revealed no monosynaptic CM excitatory postsynaptic potentials (EPSPs). The fastest descending excitation in forelimb motoneurons was disynaptically mediated via a corticoreticulospinal pathway and slowly conducted excitation via corticospinal fibers and segmental interneurons. The findings stress the importance of di- and trisynaptic excitatory corticofugal pathways to forelimb motoneurons in the control of skillful digit movements.