Does a C3-C4 propriospinal system transmit corticospinal excitation in the primate? An investigation in the macaque monkey

Abstract

1. Synaptic responses to electrical stimulation of the contralateral pyramidal tract were measured in intracellular recordings from 206 upper limb motoneurones in ten chloralose-anaesthetized macaque monkeys. The objective was to search for evidence of a disynaptic excitatory pathway via C3-C4 propriospinal interneurones similar to that in the cat. 2. In monkeys with intact spinal cords, only a small proportion of motoneurones (19%) responded with late EPSPs to repetitive stimulation of the pyramid; only 3% had segmental latencies that were appropriate for a disynaptic pathway. 3. From previous studies in the cat, it was expected that a lesion to the dorsolateral funiculus (DLF) at C5 would interrupt the corticospinal input to the spinal segments supplying upper limb muscles, whilst leaving intact excitation transmitted via a C3-C4 propriospinal system, the descending axons of which travel in the ventral part of the funiculus. In five of the monkeys a lesion was made to the DLF at C5 which spared the ventrolateral columns. It severely reduced the monosynaptic EPSPs and disynaptic IPSPs evoked from the pyramidal tract that were present in the intact monkey spinal cord, and which might have masked the presence of disynaptic EPSPs. However, even after the lesion the proportion of motoneurones with such late EPSPs was still low (18%); 14% of motoneurones had EPSPs within the disynaptic range. 4. In addition, some EPSPs with relatively long segmental latencies (> 1.1 ms) were recorded before and after the C5 lesions, but since these effects could be evoked by single stimuli, had stable latencies and did not facilitate with repetitive shocks, it is likely that they represent monosynaptic EPSPs evoked by slowly conducting corticospinal fibres which survived the lesions. 5. In seven of the monkeys motoneurone responses to stimulation of the ipsilateral lateral reticular nucleus (LRN) were also tested. Most motoneurones showed EPSPs with short latencies (1.2-2.5 ms) and other properties characteristic of monosynaptic activation. This is consistent with the presence of collaterals of C3-C4 propriospinal neurones to the LRN, as demonstrated in the cat. 6. These short-latency EPSPs evoked from the LRN were just as common before (77%) as after (75%) the C5 lesion. They had small amplitudes both before (mean +/- s.d. 1.1 +/- 0.59 mV) and after (1.2 +/- 0.72 mV) the lesion. Unlike the situation in the cat, only a small proportion (16%) of motoneurones activated from the LRN showed late EPSPs after repetitive stimulation of the pyramid. 7. The results provide little evidence for significant corticospinal excitation of motoneurones via a system of C3-C4 propriospinal neurones in the monkey. The general absence of responses mediated by such a system in the macaque, under experimental conditions similar to those in which they are seen in the cat, show that extrapolation of results from the cat to the primate should be made with considerable caution.

Figure 1. Transmission of corticospinal inputs to cat forelimb motoneurones

Stimulation of corticospinal fibres in the pyramidal tract (PT) evokes disynaptic excitation in forelimb motoneurones (MN; cervical segments C6-Th1) via propriospinal neurones (PN) which are activated monosynaptically by corticospinal fibres. These neurones are located in upper cervical (C3-C4) segments and they project monosynaptically onto MNs. Since the axons of the PNs are located in the ventrolateral funiculus, a lesion (hatched area) of the lateral corticospinal tract (LCST) at C5 abolishes any corticospinal effects on motoneurones exerted at the segmental level, but leaves intact the disynaptic excitation from C3-C4 PNs. Stimulation of the lateral reticular nucleus (LRN) evokes monosynaptic excitation in motoneurones via ascending axons of the C3-C4 PNs which project to the LRN. The same approach has been taken for the experiments in the monkey.

Figure 10. Field potential and motoneurone responses to LRN stimulation

A, field potential responses to stimulation of the lateral reticular nucleus (LRN) with different stimulation intensities (500-10 μA). Note the characteristic slow negative potential (negativity down); an early sharp negativity of unknown origin was seen with the higher intensities (200 and 500 μA). Stimulation site is indicated on the section shown in B: track 2, depth: 4 mm. Five sweeps superimposed for each intensity. Threshold of the slow negativity was 20 μA. Calibration bar = 300 μV. B, reconstruction of 4 different stimulation tracks (1-4) in a saggital section through the medulla 3.75 mm lateral to the midline. Shaded area represents the most clearly defined caudal part of the LRN. Dashed line represents the probable limits of the more dispersed rostral extension of the nucleus (Walberg, 1952). IO = inferior olive, C = caudal, R = rostral. The short bars drawn across each track indicate the depths at which stimulation was tested (mostly between 3 and 5 mm below the surface of the medulla). C, depth-threshold curves for eliciting slow negative field potentials from the tracks and stimulation sites shown in B. The lowest threshold was usually reached within or just dorsal to the LRN. Vertical arrow in B indicates the rostro-caudal position of obex. Recordings made in the deep radial motor nucleus with a low impedance glass microelectrode. E and F, short-latency EPSPs evoked from the LRN (200 μA shock) in two different deep radial motoneurones recorded in monkeys with an intact spinal cord (identification of one motoneurone shown in D). Calibration bars: 20 mV in D and 1 mV in E and F.

Figure 2. Monosynaptic excitation of motoneurones from the PT in monkeys with an intact spinal cord

Monosynaptic EPSP in a brachialis motoneurone evoked by PT stimulation. In the specimen records A-E the upper traces display intracellular records of the motoneurone (5 sweeps superimposed), the lower traces records from the surface of the spinal cord at the level of the motoneurone. In this and subsequent figures the calibration bars apply to the intracellular records: 20 mV in A and 1 mV in B-E.A, antidromic identification. B-E, responses to single (B), double (C) and triple (D) PT stimulation at 200 μA. Arrow in B indicates the period of the recording shown at an expanded time scale in E. Segmental latency (onset of EPSP after arrival of corticospinal volley in the surface recording) is 0.9 ms. F and G, distribution of segmental latencies of EPSPs recorded in the sampled motoneurones in response to single (F) and triple (G) PT stimulation at 200 μA. Three categories of response are indicated: monosynaptic EPSPs (hatched columns, n= 84 in both F and G), late EPSPs evoked by single and repetitive PT shocks (open columns, n= 9 and 7 in F and G, respectively), and late EPSPs evoked only by repetitive shocks (black columns n= 16). Unresponsive motoneurones indicated by stippled columns to left of histogram.

Figure 3. Possible disynaptic excitation from the PT in a monkey with an intact spinal cord

Late, non-monosynaptic EPSP in a deep radial motoneurone (A-D) and a radial motoneurone (E-H) evoked by PT stimulation. A and E, antidromic identification. Responses to single (B, F) and triple (C, G) PT stimulation at 200 μA. Arrows in C and G indicate the periods of the recording shown at an expanded time scale in D and H. The segmental latencies of the late effects were 2.3 ms in D and 1.4 ms in H. Calibration bars: 20 mV in A and E, 1 mV in B-H.

Figure 4. Disynaptic inhibition from the PT in monkeys with an intact spinal cord

Responses in a triceps (A-E) and a biceps (F-J) motoneurone evoked by PT stimulation. A and F, antidromic identification. Responses to single (B, G), double (C, H) and triple (D, I) PT stimulation at 200 μA. Arrows in B and G indicate the periods of the recording shown at an expanded time scale in E and J. The segmental latency of the IPSP was 1.5 ms in both motoneurones. Calibration bars: 20 mV in A and F, 1 mV in B-E and G-J. K, distribution of segmental latencies of IPSPs recorded in the sampled motoneurones (n= 76) in response to single PT stimulation at 200 μA.

Figure 5. Schematic representation of the C5 lesions made in five monkeys

Corticospinal volley in the surface recording evoked by a single PT stimulus of 200 μA is shown before and immediately after the lesion; recordings taken from a site caudal to the lesion. Note the marked reduction of the negativity (upwards) of the corticospinal volley after lesion. There was a general correspondence between the extent of the lesion and the reduction in the volley. In addition the proportion of motoneurones, sampled in the segments caudal to the lesion, which were completely unresponsive to PT stimulation was generally greater in the cases with larger lesions. Percentages of unresponsive motoneurones in each case are given in the right panel, and correspond to data obtained for single (× 1) and repetitive (× 3) PT shocks.

Figure 6. Comparison of cord dorsum recordings in the cat and monkey

A, cat. Recordings of the corticospinal volley rostral (Vr) and caudal (Vc) to a lesion at C5 (average of 10 sweeps). A single shock (top trace) evoked a corticospinal axonal volley which was abolished by the lesion (see caudal recording, Vc). Repetitive shocks evoked an additional synaptic discharge (arrowed) of presumed propriospinal origin which survived the lesion. In the monkey (B), this synaptic volley was not seen; instead, a small positivity was recorded (arrowhead). The C5 lesion did reduce greatly the corticospinal axonal volley. Calibration bars: 100 μV.

Figure 7. Monosynaptic excitation of motoneurones from the PT in monkeys with a C5 lesion

Monosynaptic EPSP in a deep radial motoneurone (A-E) and late EPSP in brachialis motoneurone (F-J) evoked by PT stimulation of 200 μA. A and F, antidromic identification. Responses to single (B, G), double (C, H) and triple (D, I) PT stimulation. Arrows in B and G indicate the periods of the recording shown at an expanded time scale in E and J. The segmental latencies of the effects were 0.9 ms in E and 1.4 ms in J. Calibration bars: 20 mV in A and F, 1 mV in B-E and G-J.K and L, distribution of segmental latencies of EPSPs recorded in the sampled motoneurones in response to single (K, n= 90) and triple (L, n= 90) PT stimulation at 200 μA. Key as in Fig. 2

Figure 9. Amplitude distribution of EPSPs evoked from the PT before and after the C5 lesion

Responses to 200 μA PT stimulation before (A, B) and after (C, D) a C5 lesion. A and C, amplitudes of monosynaptic and late EPSPs evoked by single PT stimulation before (A) and after (C) the lesion. B and D, amplitudes of late EPSPs that were evoked by repetitive PT stimulation before (B) and after (D) lesion.

Figure 8. Possible disynaptic excitation from the PT in monkeys with a C5 lesion

Late non-monosynaptic EPSP in a deep radial motoneurone (A-E) and in a biceps motoneurone (F-J) evoked by PT stimulation of 200 μA. A and F, antidromic identification. Responses to single (B, C), double (C, H) and triple (D, I) PT stimulation at 200 μA. Arrows in D and I indicate the periods of the recording shown at an expanded time scale in E and J. The segmental latencies of the late effects were 1.8 ms in E and 1.6 ms in J. Calibration bars: 20 mV in A and F, 1 mV in B-E and G-J.

Figure 13. Proportion of responses to PT and LRN stimulation in motoneurones recorded before and after a C5 lesion

Response categories for PT data: monosynaptic EPSP, with a segmental latency < 1.2 ms; late EPSP, segmental latency of (>= 1.2 ms and evoked by PT × 3 but not by PT × 1 (black columns are late EPSPs in the disynaptic range, 1.3-1.9 ms). IPSP, recorded in motoneurones with or without preceding EPSP. Total number of motoneurones tested for each condition given at base of each column. The C5 lesion caused a large reduction in the proportion of EPSPs and IPSPs evoked from the PT, but there was little effect on either the late EPSPs from the PT, or on effects from the LRN.

Figure 12. Comparison of motoneurone responses to stimulation of the PT and LRN after the C5 lesion

A-D, biceps motoneurone with an EPSP from the LRN and a late EPSP at a disynaptic latency from the PT. The LRN-evoked EPSP had a latency of 1.5 ms (A). Single PT stimuli did not evoke any effects (C), but triple shocks produced a late EPSP, with a segmental latency of 1.6 ms (D). All stimulation intensities were 200 μA. Calibration bars in all panels: 1 mV. E-H, responses in a median motoneurone to single (E and G) and triple (F and H) stimuli delivered to the LRN (E and F) and PT (G and H) with 200 μA shocks. The EPSP from the LRN had a latency of 1.4 ms. A later EPSP (arrowed) was evoked by repetitive stimulation (F). Neither single nor repetitive PT stimulation evoked any response in this motoneurone.

Figure 11. Properties of EPSPs evoked from the LRN before and after the C5 lesion

A, distribution of absolute latencies of EPSPs recorded in monkeys before (upper histogram) and after a C5 DLF lesion from 43 and 67 motoneurones, respectively, in response to single LRN stimuli of 200 μA. One motoneurone yielded both an early and a late EPSP. Stippled columns at extreme left: motoneurones unresponsive to LRN (no EPSP). The black columns represent those motoneurones with late EPSPs evoked by repetitive (3 ×) but not single PT stimuli. B, distribution of rise times of EPSPs evoked by stimulation of the LRN at 200 μA in 39 motoneurones before the lesion (upper histogram) and in 62 motoneurones after it. EPSPs were not contaminated by ensuing IPSPs. C, distribution of EPSP amplitudes in these same motoneurones.