Direct and indirect connections with upper limb motoneurons from the primate reticulospinal tract

Abstract

Although the reticulospinal tract is a major descending motor pathway in mammals, its contribution to upper limb control in primates has received relatively little attention. Reticulospinal connections are widely assumed to be responsible for coordinated gross movements primarily of proximal muscles, whereas the corticospinal tract mediates fine movements, particularly of the hand. In this study, we used intracellular recording in anesthetized monkeys to examine the synaptic connections between the reticulospinal tract and antidromically identified cervical ventral horn motoneurons, focusing in particular on motoneurons projecting distally to wrist and digit muscles. We found that motoneurons receive monosynaptic and disynaptic reticulospinal inputs, including monosynaptic excitatory connections to motoneurons that innervate intrinsic hand muscles, a connection not previously known to exist. We show that excitatory reticulomotoneuronal connections are as common and as strong in hand motoneuron groups as in forearm or upper arm motoneurons. These data suggest that the primate reticulospinal system may form a parallel pathway to distal muscles, alongside the corticospinal tract. Reticulospinal neurons are therefore in a position to influence upper limb muscle activity after damage to the corticospinal system as may occur in stroke or spinal cord injury, and may be a target site for therapeutic interventions.

Figure 1.

Positioning of PT and MLF stimulating electrodes. A–D show histological verification of stimulation sites from one animal. A and C show whole brainstem sections with lesions at the tips of the MLF and PT electrodes, respectively. XII, Hypoglossal nucleus. The tip positions are visible in B and D, which show the regions marked by boxes from A and C at higher magnification. E–G show an example of the occlusion test used to aid positioning of MLF stimulating electrodes. All panels show epidural recordings from the dorsal surface of the cervical spinal cord. Brackets enclose volley responses. Arrows indicate point of stimulus delivery. E, Following a 300 μA stimulus delivered through MLF electrode. F, Following a 300 μA stimulus delivered through PT electrode. G, Following combined stimulation of PT and MLF with 400 μs separation (MLF first). The red trace shows arithmetic sum of E and F, while the black trace shows the recorded volley. The near perfect overlay indicates an absence of occlusion, strongly implying that the responses were mediated by independent fiber tracts. Calibrations in E apply to E–G. N values indicate number of stimuli.

Figure 2.

Cervical spinal motoneurons receive monosynaptic and disynaptic reticulospinal input. A–E, Example motoneuron projecting to forearm flexors that received disynaptic reticulospinal contacts. A, Antidromic activation from median nerve above the elbow (overlain single sweeps). B–D, Disynaptic reticulospinal EPSPs following single 300 μA MLF stimulus (B), train of three stimuli (C), and train of four stimuli (D). Each panel shows averaged intracellular records (top) with simultaneously recorded epidural volleys below. Vertical dashed lines highlight the segmental latency of the response. Calibrations in B apply to B–D. E, EPSP evoked in this cell following single 300 μA stimulus to PT. F–J, Example monosynaptic EPSPs evoked following reticulospinal activation in a spinal motoneuron also projecting to forearm flexors. Panels and plotting conventions are as in A–E. K–O, Example motoneuron projecting to thenar muscles which received powerful monosynaptic input from the reticulospinal tract. Panels and plotting conventions are as in A–E, except that responses to a train of two and three stimuli are shown in M and N, respectively.

Figure 3.

Population data. A–D, Histograms of incidence (left) and mean amplitude (right) of monosynaptic EPSPs from the PT (PT mono), monosynaptic EPSPs evoked from the MLF (MLF mono), and disynaptic EPSPs from the MLF (MLF di). The numbers above each column in the incidence plots give the raw numbers of motoneurons. Error bars in amplitude plots are SEM. Amplitudes of disynaptic EPSPs are measured from the response to the last of a train of three or four shocks.