How to enhance ipsilateral actions of pyramidal tract neurons

Abstract

We have shown previously that ipsilateral pyramidal tract (PT) neurons facilitate the actions of reticulospinal neurons on feline motoneurons (Edgley et al., 2004), which indicates that they might assist the recovery of motor functions after injuries of contralateral corticospinal neurons. Nevertheless, stimulation of ipsilateral PT fibers alone only rarely evoked any synaptic actions in motoneurons. The aim of this study was to investigate possible ways of enhancing such actions and of inducing more effective excitation and inhibition of motoneurons. The effects of stimulation of the ipsilateral PT were investigated after eliminating the spinal actions of contralateral PT fibers by hemisecting the spinal cord at a low thoracic level and were estimated from intracellular records from hindlimb motoneurons. Two measures were used to enhance PT actions. The first was to increase the probability of activation of reticulospinal neurons by mutual facilitation of actions of ipsilateral and contralateral PT neurons. The second was to enhance synaptic transmission between PT neurons and reticulospinal neurons, and in pathways between the reticulospinal neurons and motoneurons via commissural interneurons, by systemic application of a K+ channel blocker, 4-aminopyridine (4-AP). The results show that under favorable conditions, ipsilateral PT neurons may induce EPSPs and IPSPs in hindlimb motoneurons, or even action potentials, via the reticulospinal pathway. This study strengthens previous conclusions that ipsilateral PT neurons can potentially replace, at least to some extent, the actions of injured contralateral PT neurons. It also suggests that 4-AP might improve the progress of the recovery.

Figure 1.

Mutual facilitation of actions from the two pyramids. A, B, Simplified diagrams of connections between pyramidal tract fibers and ipsilateral hindlimb motoneurons, via reticulospinal neurons and commissural interneurons [Edgley et al. (2004), modified from their Fig. 1]. Circles represent RS neurons, lamina VIII commissural neurons (VIII), and hindlimb motoneurons (MN) with which commissural interneurons form synaptic contacts. They show that both the left (L) and right (R) PT fibers may excite RS neurons projecting via the right medial longitudinal fascicle and that these neurons may be excited either monosynaptically or disynaptically (via other RS neurons). C, D, Reconstructions of the locations of the PT and MLF stimulating electrodes, as defined by the electrolytic lesions made at the end of the experiments. These are superimposed on representative sections of the brainstem cut in the plane of the electrode insertions. E-G, Intracellular records from a PBST motoneuron (top traces) and the associated records from the cord dorsum (bottom traces); averages of 20 records. In this and all other figures, the negativity is downward for microelectrode records and upward for records from the cord dorsum. Voltage calibration is for intracellular records.

Figure 2.

Enhancement of excitatory synaptic actions from pyramids after 4-AP. Intracellular records from GS (A-D) and Sart (E-H) motoneurons (top traces) and from the cord dorsum (bottom traces). Gray traces are control records. Black traces are records taken after systemic application of 4-AP (0.33 and 0.2 mg/kg); intracellular recordings were maintained from the same motoneurons. Dotted lines indicate onset of the earliest EPSPs or IPSPs evoked before and after 4-AP, respectively. Other indications are as in Figure 1.

Figure 3.

Relations between synaptic actions evoked from the MLF and from the left and right PTs. A-F, Descending volleys evoked by stimuli applied in the right MLF and in the left and right PTs. All were evoked by four stimuli, but only those after the fourth stimuli (at an expanded time base) are shown in A and B. Arrows indicate direct volleys at the C3 segmental level that are very small (from the MLF) or not detectable (from PTs) at a lumbar level. A, B, Dotted lines indicate delays of positive peaks of the first (direct) and the second and third (relayed) C3 PT volleys with respect to the direct MLF volleys. D-F, Dotted lines indicate delays between the first relayed PT and MLF volleys. G-L, Intracellular records from Q and Sart motoneurons (top traces) and corresponding records from the cord dorsum (bottom traces) in the same experiment. Note distinct EPSPs or IPSPs after individual second to fourth or third and fourth stimuli in G-I and J-L, respectively. Note also the similar delays of both the relayed PT volleys and PSPs evoked by PT stimuli with respect to PSPs from the MLF.

Figure 4.

Latencies and amplitudes of EPSPs and IPSPs evoked from the left and right PTs. A-C, F, Latencies of EPSPs (filled symbols) and IPSPs (open symbols) evoked from the left and right PTs stimulated separately or jointly and from the MLF. The data points show the latencies of PSPs evoked in individual motoneurons by different parameters of stimuli (with 1-5 tests per motoneuron). They are ranked from the shortest to the longest. D, E, Data points in A and B are subdivided, being ranked for EPSPs evoked by different numbers of stimuli (indicated below). A-C, Thick gray lines indicate ranges of latencies of EPSPs evoked from the MLF. Dotted lines indicate latencies of PT EPSPs (up to 2.5 ms longer than EPSPs from the MLF) that are compatible with being mediated by either the first or the second relayed volleys illustrated in Figure 3B. No statistically significant differences were found between latencies of EPSPs or IPSPs evoked by joint (C) and either left or right PT stimulation. These were 6.42 ± 0.25, 6.72 ± 0.9, and 6.07 ± 0.15 ms (mean ± SEM) from the effective stimulus, respectively. Differences between latencies of PSPs evoked from the left and right PTs were significant at p < 0.02. G-J, Histograms of amplitudes of EPSPs evoked by trains of near-maximal PT stimuli (4-5 before and 3-4 after application of 4-AP). Only motoneurons with action potentials >45 mV were used for the comparison. Student's t test does not indicate statistically significant differences between effects from the left and right PTs in G and I but does indicate highly statistically significant differences between effects evoked before and after application of 4-AP (see Results).