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NEUROSCIENCE |
1 Department of Physiology, Göteborg University, 405 30 Göteborg Sweden
2 Department of Anatomy, Cambridge University CB2 3DY, UK
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Abstract |
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(Received 27 April 2006;
accepted after revision 31 May 2006;
first published online 1 June 2006)
Corresponding author E. Jankowska: Department of Physiology, Medicinaregatan 11, Box 432, 405 30 Göteborg, Sweden. Email: elzbieta.jankowska{at}physiol.gu.se
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Introduction |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Methods |
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The experiments were performed on eight deeply anaesthetized cats weighing 2.9–4.7 kg. All experimental procedures were as previously described (Edgley et al. 2004; Jankowska et al. 2005a), and were approved by the local Ethics Committee (Göteborgs djurförsöksetiska nämnd) and followed NIH and EU guidelines for animal care. Briefly, anaesthesia was induced with sodium pentobarbital (40–44 mg kg–1, I.P.) and maintained with intermittent doses of 
-chloralose (Rhône-Poulenc Santé, France; 5 mg kg–1; administered every 1–2 h, up to 55 mg kg–1, I.V.). Additional doses of -chloralose were given when increases in continuously monitored blood pressure or heart rate were evoked by peripheral or central stimulation, or if the pupils dilated. During recordings, neuromuscular transmission was blocked by pancuronium bromide (Pavulon, Organon, Sweden; about 0.2 mg kg–1 h–1, I.V.) and the animals were artificially ventilated. The effectiveness of synaptic transmission was increased by intravenous application of 4-AP in doses 0.2–0.4 mg kg–1, I.V. The experiments were terminated by a lethal dose of pentobarbital resulting in cardiac arrest.
A laminectomy exposed the third to seventh lumbar (L3–L7), low thoracic (Th11–Th13) and the third cervical (C3) segments, and the spinal cord was hemisected on the right side at low thoracic level. A number of peripheral nerves were dissected free and mounted on stimulating electrodes. They included the quadriceps (Q) and sartorius (Sart) branches of the left and right femoral nerve and of the right gastrocnemius–soleus (GS) nerve (mounted in subcutaneous cuff electrodes), and sometimes branches of the left sciatic nerve: posterior biceps and semitendinosus (PBST), anterior biceps and semimembranosus (ABSM), GS, plantaris (PL), flexor digitorum and hallucis longus (FDL), and deep peroneal (DP) including extensor digitorum longus and anterior tibial nerves.
Stimulation
Axons of commissural interneurones located on the left side of the spinal cord were stimulated using tungsten electrodes placed within the right GS motor nuclei. The electrodes were introduced through a hole in the dura overlying the dorsal columns at the level of the caudal part of the L7 segment, and left at the depth at which the field potential evoked by stimulation of the GS nerve was maximal. Projections of the interneurones to these motor nuclei were demonstrated by their antidromic activation in response to stimuli of 10–100 µA. Stimulation of the lateral funiculi at the thoracic level (up to 1 mA) was used to identify and exclude any neurones projecting rostral to the lumbar enlargement. The peripheral nerves were stimulated at intensities up to five times threshold (5T) for group I afferents; the threshold was defined as stimulus intensity at which just visible afferent volleys appeared in records from the cord dorsum.
Tungsten electrodes were placed in the left MLF (ipsilateral with respect to commissural interneurones) at the level of the inferior olive (Horsley-Clarke coordinates posterior 8–9, lateral 0.6–1.0 and horizontal –5 to –7) and either in both, or only in the right (contralateral) PT at the level of the superior olive (Horsley-Clarke coordinates posterior 5–6, lateral 0.7–1.2 and horizontal about –10.5).The electrodes were inserted through the cerebellum (at an angle of 35 deg) and left at sites from which maximal descending volleys were evoked at threshold stimulus intensities of 20 µA or less. The descending volleys were recorded monopolarly with a ball electrode in contact with the dura from the C3 and Th12 segments caudal to the hemisection. The stimulation sites were marked with electrolytic lesions at the end of the experiment and verified histologically (Fig. 1B and C). For activation of reticulospinal and corticospinal tract fibres, constant current cathodal stimuli (0.2 ms, 50–200 µA) were used. Near maximal stimuli applied in MLF were expected to activate a large proportion of ponto- and medullary reticulospinal tract fibres (see Jankowska et al. 2003). These stimuli could also activate the medial vestibulospinal tract fibres (which do not project caudally as far as the lumbar segments) but would not activate fibres of the lateral vestibular tract (Aoyama et al. 1971; Hongo et al. 1975). Effects of MLF stimuli in the lumbar segments could thus be attributed to reticulospinal fibres.
Descending volleys evoked by PT stimuli could be differentiated from those evoked by stimulation of the MLF by their longer latency in records from the C3 cervical segment and their considerable asynchrony at the Th12 level. By utilizing these differences it was possible to ensure that no spread of current occurred from the final position of the stimulating electrode in the PT to the MLF, even when stimulus intensity was 200 µA. As shown in Fig. 2A and B, when the electrode was correctly placed, neither short latency C3 volleys, nor any volleys at the Th12 level, were evoked from within the PT or from the area at least 1.8 mm above the dorsal border of the PT.
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Recording and analysis
Glass micropipettes filled with 2 M solution of potassium citrate (2–5 M
) were used for intracellular or extracellular recording, except in one experiment in which they were obtained with pipettes filled with a mixture of rhodamine-dextran and Neurobiotin, used for labelling and subsequent morphological and immunocytochemical analyses (Bannatyne et al. 2003). Some extracellular records were also obtained with glass micropipettes filled with a 2 M solution of sodium chloride (1–2 M). Both the original data and averages of 10–20 single records (with the time resolution of 20 or 30 µs per address) were stored on-line using a software sampling and analysis system designed by E. Eide, T. Holmström and N. Pihlgren (Göteborg University). Differences between samples of neurones were assessed for statistical significance using Student's t test (for paired and/or unpaired, normally distributed data).
Sampling
The sample of commissural interneurones analysed in this study included 29 intracellularly recorded interneurones located in the L3–L5 segments. Nine of these and nine other interneurones were also recorded extracellularly. They were concluded to be activated antidromically from the contralateral motor nuclei on the basis of a constant response latency (0.5–1.4 ms), most of which (in particular those < 1 ms) were in addition too short to allow a synaptic delay. Action potentials classified as evoked antidromically were collided by preceding synaptically evoked responses in extracellular records and appeared in an all-or-none fashion in intracellular records. The longest latencies of antidromic activation (1.2–1.4 ms) corresponded to conduction velocities of about 25–30 m s–1 and the shortest to velocities of 50 m s–1. The search was made for commissural interneurones with monosynaptic input from either the MLF or group II afferents, both ipsilateral with respect to the interneurones, at locations at which largest field potentials from both sources were recorded. At some of these locations field potentials were also evoked from either one or both PTs.
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Results |
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EPSPs were evoked by PT stimulation in the majority of commissural interneurones that had monosynaptic input from the MLF. When short trains of stimuli of 150 µA were used they were evoked from both the contralateral and the ipsilateral PT in more than 75% of these interneurones. As shown in Figs 3 and 4, distinct EPSPs followed successive PT stimuli, and the first step in the analysis was linking them to the individual stimuli. When an EPSP appeared after a second or third stimulus, the number of stimuli in the train was reduced to define which stimulus was responsible for it. The double-headed arrows in Fig. 3A indicate which of the stimuli evoked the successive EPSPs.
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150 µA were on average 33 and 51% of those evoked by the third contralateral PT stimuli, and 42 and 61% of those evoked by the third ipsilateral PT stimuli. The smaller amplitudes of EPSPs evoked by the first two stimuli would explain why extracellularly recorded action potentials (see below) usually appeared only to the third or fourth stimulus. Extracellular field potentials (reflecting intracellular EPSPs) evoked by PT stimulation were recorded at 36 different locations. Like EPSPs evoked in individual commissural interneurones, distinct temporally facilitated field potentials were evoked by successive PT stimuli. They were usually detectable only after the second and third stimuli of a train (Fig. 3A), even at maximal stimulus intensity. This contrasted with field potentials evoked by MLF stimulation which were evoked by the first as well as the successive stimuli and were of similar amplitude in response to each stimulus (Fig. 3C). When evoked by stimuli not exceeding 150 µA, field potentials were induced from both the contralateral and ipsilateral PT at latencies 1.4–1.7 ms longer than latencies of field potentials evoked from the MLF (Fig. 5A; Table 2B, columns 5 and 6).
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In order to relate EPSPs evoked in commissural interneurones to either monosynaptic, disynaptic or polysynaptic activation of RS neurones by PT stimuli, we used recordings from the MLF to monitor activity in RS neurones. The records were obtained using the same electrode with which RS fibres were stimulated. In all five experiments in which this was done, the effects of PT stimuli were similar. The stimuli evoked first small triphasic volleys at about 0.5 ms latency (upward arrowheads in Fig. 6A and B), most probably reflecting action potentials in collaterals of PT fibres. These were followed by population potentials (at about 0.9 ms from the stimulus) on which asynchronous spike discharges were superimposed, especially after the second or third stimuli. The earliest discharges appeared at latencies of 1.1–1.6 ms from the stimuli, but less than 1 ms from the triphasic volleys, and could therefore have been due to monosynaptically evoked activation of RS neurones. These were followed by discharges evoked at about 2–3 ms and 5–10 ms latencies from the stimuli and attributable to disynaptically and polysynaptically evoked activation of RS neurones. PT stimuli could thus activate RS neurones monosynaptically, disynaptically and polysynaptically.
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A closer inspection of EPSPs evoked by PT stimulation revealed that the earliest components were often followed by components with onsets 1–2 ms later; such later components can be seen both in individual and averaged records (indicated by the fourth dotted line in Fig. 6E–H). We related, therefore, the two components of EPSPs evoked by PT stimuli to the earliest and most likely disynaptic discharges of RS neurones evoked by PT stimuli and compared their timing.
The earliest components of EPSPs evoked by PT stimuli had latencies (Table 2C, columns 2 and 3) that nearly equalled the sums of latencies of the earliest discharges recorded in the MLF and of latencies of EPSPs evoked from the MLF, as indicated to the right of the diagram in Fig. 6I. This is illustrated by the close correspondence between the delays of EPSPs of PT origin with respect to those evoked from the MLF in a commissural interneurone and the latencies of discharges of RS neurones in MLF (first two dotted lines in Fig 6A and B). The data in Table 2B, columns 5 and 6, show further that the longer latencies of EPSPs and field potentials of PT than of MLF origin (1.4–1.7 ms) match the 1.1–1.6 ms latencies of the earliest discharges of RS neurones recorded in the MLF. We propose, therefore, that the earliest EPSPs were induced via monosynaptically excited RS neurones.
The later components of EPSPs following the monosynaptic EPSPs might in a similar way be related to the disynaptically evoked discharges of RS neurones, and reflect trisynaptic rather than disynaptic coupling between PT neurones and commissural interneurones. One could expect longer latency activation when RS neurones are less excitable and when their activation by PT neurones requires summation of mono- and disynaptically evoked EPSPs. Polysynaptically evoked excitation of RS neurones (the late discharges in Fig. 6A and B) might also summate with early effects of the third and fourth PT stimuli and increase the effectiveness of the successive PT stimuli. Using the above arguments we may thus set the borderline between latencies of disynaptic and trisynaptic actions of PT stimuli plotted in Fig. 5B at about 5 ms from the stimuli, even if this borderline is somewhat arbitrary.
One of the consequences of the postulated collateral actions of RS neurones on other RS neurones would be that stimuli applied in the MLF should not only give rise to descending volleys but also to synaptically evoked activation of RS neurones. Monosynaptic actions of fibres stimulated in MLF on commissural interneurones should thus be followed by disynaptically evoked PSPs, as has indeed been found and is illustrated in Fig. 7. Records in Fig. 7A and B show the expected temporal facilitation of the second components of these EPSPs. Comparison of the timing of these components in Fig. 7B with the timing of the disynaptic and trisynaptic components of EPSPs evoked by PT stimuli in Fig. 7E shows a good match. Finally, comparison of the timing of EPSPs evoked by MLF stimuli that were too weak to activate fibres responsible for monosynaptic EPSPs in the interneurone illustrated in Fig. 7C, with the two components of EPSPs evoked by stronger stimuli in Fig. 7D, shows that the EPSP in Fig. 7C and the second component of the EPSP in Fig. 7D coincided. Following the same reasoning, one may conclude that even if PT stimuli are too weak to evoke monosynaptic activation of RS neurones, they may activate RS neurones disynaptically, via other brainstem neurones, and induce trisynaptic EPSPs in commissural interneurones via the same RS neurones.
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PT stimuli evoked IPSPs in practically all of the commissural interneurones in which IPSPs were evoked by MLF stimulation. However, in several interneurones the IPSPs of PT origin were less prominent than the IPSPs evoked from the MLF, as in interneurones illustrated in Figs 4 and 8, and often required at least two maximal PT stimuli to appear (Fig 8A and B). As in the case of the EPSPs, when stronger PT stimuli were used, IPSPs were evoked by earlier stimuli, and/or were larger (Fig. 8D and E).
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Coupling between PT neurones and commissural interneurones without monosynaptic input from the MLF
The subpopulation of nine commissural interneurones that were not monosynaptically excited from the MLF (Table 2D) appeared to include interneurones of two categories: interneurones with monosynaptic input from group II afferents (Jankowska et al. 2005b), and interneurones with monosynaptic input from group I and II afferents (Jankowska & Noga, 1990). However, group I input was tested from only a small selection of peripheral nerves and could not be excluded in the four interneurones in which only group II was found. All these interneurones will therefore be considered jointly.
Table 2 shows that stimulation of both the contralateral and ipsilateral PT evoked EPSPs and IPSPs in this subpopulation of commissural interneurones. However, two main differences have been found in PT actions on commissural interneurones lacking monosynaptic input from the MLF and those described above. Firstly, EPSPs evoked in these commissural interneurones appeared at latencies more than 1 ms longer than those in interneurones with monosynaptic MLF EPSPs (Table 2D). However, these latencies exceeded latencies of EPSPs evoked from the MLF to the same extent as in interneurones with monosynaptic input from the MLF.
Secondly, latencies of IPSPs evoked in them did not exceed latencies of the EPSPs, latencies of the IPSPs being similar to the latencies of IPSPs evoked in interneurones with monosynaptic EPSPs from the MLF. It appears thus that IPSPs evoked in the two subpopulations of commissural interneurones might be mediated by the same interneurones and be related to monosynaptically rather than disynaptically evoked PT excitatory actions on RS neurones.
Extracellularly recorded responses
Extracellular records were obtained from 18 commissural interneurones, nine of which were subsequently penetrated. They were activated more effectively by MLF stimuli (first to third stimulus) than by PT stimuli (third to fifth stimulus). Activation of these interneurones thus required temporal facilitation to a greater extent when they were evoked from PTs than from the MLF.
The spikes had a tendency to coincide with the peak or the declining phases of field potentials evoked by the same stimuli, but their latencies varied greatly, as illustrated in Fig. 10A–C. However, the minimal latencies exceeded latencies of EPSPs evoked by the same stimuli in the subsequently penetrated neurones by 0.99 ± 0.30 ms for those from the contralateral PT, 0.53 ± 0.20 ms from the ipsilateral PT, and 0.29 ± 0.03 ms from the ipsilateral MLF, as illustrated in Fig. 10G–I. The earliest action potentials are thus compatible with monosynaptic activation of commissural interneurones from the MLF and disynaptic from the PTs.
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Discussion |
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-motoneurones (Bannatyne et al. 2003; Butt & Kiehn, 2003; Matsuyama et al. 2004). However, not all PSPs evoked by PT stimulation in hindlimb motoneurones were found to be evoked at latencies compatible with trisynaptic coupling (Jankowska et al. 2005a) and the longer latencies of other PSPs might involve additional neuronal relays at either brainstem or spinal levels. Additional brainstem relays would be in keeping with the finding that reticulospinal neurones are excited by PT neurones not only directly but also indirectly (Peterson et al. 1974; Ito & McCarley, 1987; Canedo & Lamas, 1993) and also with disynaptic excitation of commissural interneurones by MLF stimuli (Krutki et al. 2003) which could be explained either by re-excitation of RS neurones via their brainstem target neurones or by involvement of additional spinal relays. Longer latency PSPs evoked by PT stimuli could also reflect actions of slower conducting corticoreticular (Peterson et al. 1974; Matsuyama & Drew, 1997) and/or reticulospinal neurones (He & Wu, 1985; Mitani et al. 1988a), or of a relatively inefficient synaptic activation of RS neurones and commissural interneurones. Whether any other commissural interneurones, in addition to those with input from RS neurones and/or from group II muscle afferents analysed in the present study, mediate PT actions to motoneurones remains still an open question. However, as indicated in the next section they would be unlikely to contribute to the shortest latency PT actions. Mode of excitation of commissural interneurones by PT stimuli
Our estimates of the timing of PT actions on commissural interneurones required first finding which particular stimulus in a train was responsible for the PT actions, as illustrated in Figs 3, 8 and 9. These were usually the third or fourth stimuli for action potentials, and the first or second stimuli for EPSPs and IPSPs. The minimal latencies of these PSPs of PT origin were then measured and compared with minimal latencies of PSPs evoked from the MLF and related to the timing of effects of PT neurones on reticulospinal neurones (monitored by recording from fibres running in the MLF). Taken together, the results led to the conclusion that latencies of PSPs evoked by PT stimuli that were less than 2 ms longer than those of PSPs evoked by MLF stimuli are compatible with actions mediated by RS neurones that were monosynaptically activated by PT stimuli. In turn, this led to the conclusion that contralateral as well as ipsilateral PT fibres may provide disynaptic input to commissural interneurones with monosynaptic input from the MLF. However, the earliest components of EPSPs evoked from either PT were often followed by later components, especially after the third or fourth stimuli, which are more effective in indirectly activating reticulospinal neurones. It cannot therefore be resolved whether disynaptic EPSPs of PT origin are sufficient to induce action potentials in commissural interneurones or whether summation of di- and trisynaptically evoked EPSPs and/or of late actions of the earlier PT stimuli is needed for the EPSPs to reach action potential threshold. The most reasonable conclusion might be that disynaptically mediated excitation of commissural interneurones by PT neurones contributes to trisynaptic PT actions on motoneurones on a background of PT effects mediated by additional supraspinal relay neurones.
This conclusion is in agreement with several sets of previous data, e.g. the range of latencies (2.4–30 ms) of spike activation in RS neurones by cortical stimuli reported by Peterson et al. (1974) shows that the earliest of these latencies were only slightly longer than latencies of indirect volleys recorded in MLF in our study (2 ms), even though they involved a longer conduction distance. The ranges of latencies of EPSPs evoked in reticulospinal neurones by single stimuli (0.8–1.6 and 1.7–2.4 ms) in the study of Peterson et al. (1974) show an even closer correspondence. Of particular interest for identifying the reticular relays of corticospinal actions is that EPSPs likely to be evoked mono- and disynaptically were found in RS neurones in both pontine and medullary nuclei (Peterson et al. 1974), that EPSPs evoked at shortest latencies (< 2 ms) were found primarily in the fastest conducting RS neurones (He & Wu, 1985). It is also of relevance that both corticospinal neurones and other PT neurones were found to evoke monosynaptic EPSPs in RS neurones, while disynaptic EPSPs followed activity of the latter, but not of the former (Canedo & Lamas, 1993).
Considering that all commissural interneurones with monosynaptic input from RS neurones (but not those with disynaptic input) were disynaptically excited from PTs suggests that the earliest (trisynaptic) PT actions on hindlimb motoneurones are mediated primarily via the former. However, commissural interneurones without monosynaptic input from RS neurones (e.g. commissural interneurones which mediate crossed reflexes from group I and II muscle afferents; see Jankowska & Noga, 1990; Jankowska et al. 2005b) could contribute to later PT actions and these might be further enhanced by nerve impulses induced during muscle stretches and/or contractions as sensory feedback. Involvement of all these mutually enhancing sources of input to reticulospinal neurones and commissural interneurones should be of particular use for recovery of functions after central injuries when the effectiveness of activation of PT neurones and of their actions on RS neurones is reduced.
Even though all of the reported results support the mediation of the excitatory actions of PT neurones on commissural interneurones by RS neurones, it should be considered that RS neurones are not the only neurones via which PT neurones may excite commissural interneurones.
One alternative route of PT actions might be via vestibulospinal neurones in view of the demonstration that neurones in the lateral vestibular nucleus provide both monosynaptic and disynaptic input to commissural interneurones (Krutki et al. 2003) as well as the evidence for direct cortico-vestibular projections from the areas 6, 3 and 2a (Wilson et al. 1999). However, Wilson et al. (1999) suggested that cortical neurones activate vestibulospinal neurones polysynaptically rather than monosynaptically and, if so, vestibulospinal neurones might contribute to the later but not the earliest PT actions on commissural interneurones.
Other alternative relay neurones mediating PT actions on commissural interneurones might be spinal interneurones that are monosynaptically excited by PT neurones and have commissural neurones as their target cells. So far we have no direct evidence either for or against this possibility. However, we might consider that conduction velocity of the PT fibres is lower than of the RS tract fibres. For the fastest conducting PT neurones (with conduction velocity of about 60 m s–1; Lloyd, 1941) the conduction time to midlumbar segments would thus be about 1.5 times longer than for RS neurones (conducting at 90–100 m s–1). For slower conducting PT neurones (e.g. conducting at about 30 or 20 m s–1) it would be about 3–4 times longer. After subtracting about 0.5 ms for the latent period of generation of action potentials in the stimulated axons and one synaptic delay from the latencies of the PSPs, the conduction time along axons of RS neurones would amount to about 2.5 ms. By multiplying it by 1.5 and 3 and adding 0.5 ms, the fastest and slower conducting PT fibres might be predicted to act monosynaptically at latencies of 4.25 and 8 ms, respectively, and disynaptically at latencies of about 5.25 and 9 ms (making allowance for about 1 ms for conduction time along axons of the interposed interneurones and one additional synaptic delay). The earliest pyramidal volleys might thus reach the lumbosacral enlargement and exert monosynaptic actions at latencies of about 4 ms, which is in keeping with the original observations of Lloyd (1941). Disynaptic actions via spinal interneurones would then be expected after an additional millisecond (about 5 ms), and later actions over several milliseconds. Latencies of the earliest disynaptic excitatory PT actions (about 5 ms) would thus be within the range of latencies of later components of EPSPs evoked in commissural interneurones by PT stimuli and would allow these components to be evoked disynaptically via spinal neurones, rather than trisynaptically via RS neurones. However, this would require that some interneurones exciting commissural interneurones are activated by PT fibres at latencies of 4–5 ms, whilst the shortest reported latencies of monosynaptic EPSPs evoked from the contralateral motor cortex in spinal interneurones were of 6–8 ms (Lundberg et al. 1962) and latencies of responses of unspecified dorsal horn and intermediate zone interneurones much longer (9–20 ms; Lloyd, 1941). Until any suitable spinal relay neurones are found, the most plausible explanation of the di- and trisynaptic actions of PT neurones on commissural interneurones will remain that they are mediated primarily via RS neurones.
Inhibition of commissural interneurones
In the majority of commissural interneurones, inhibition was evoked in parallel by contralateral PT and ipsilateral MLF stimuli, indicating that PT neurones activate reticulospinal neurones with inhibitory as well as excitatory actions. Since there are no indications for projections of inhibitory reticulospinal neurones to the lumbar segments (Grillner et al. 1968; Wilson & Yoshida, 1968, 1969; Peterson, 1979) and the minimal latencies of IPSPs are about 1 ms longer than of EPSPs, these IPSPs should be mediated by spinal inhibitory neurones activated by reticulospinal neurones. Theoretically, these inhibitory interneurones might include inhibitory commissural interneurones (Bannatyne et al. 2003) and the inhibition be considered as an expression of inhibitory interactions between commissural interneurones. However, this is unlikely because commissural interneurones with input from RS neurones appear to lack local axon collaterals (Bannatyne et al. 2003; Matsuyama et al. 2004) via which they might act before they cross. Inhibition should thus be mediated by other, so far unidentified, inhibitory interneurones, possibly including both intermediate zone and ventral horn interneurones contacted by reticulospinal fibres (Takakusaki et al. 1989, 2001; Davies & Edgley, 1994).
The sequences of IPSPs preceding EPSPs would be particularly well suited for feed-forward modulation of actions of commissural interneurones, especially when the IPSPs are evoked at lower thresholds than the EPSPs. They could thus set the balance between descending and peripheral inputs to commissural interneurones and increase the relative importance of the excitatory input from muscle afferents. Small amplitude IPSPs of PT origin would more effectively interfere with similarly small EPSPs of PT origin than with much larger EPSPs from group II afferents. The IPSPs might nevertheless add to other means of weakening reflex actions from muscle afferents by reticulospinal neurones while assisting in movements induced by descending commands (see Lundberg, 1982; Noga et al. 1992; Riddell et al. 1993).
Relative importance of contralateral and ipsilateral PT neurones for PT actions mediated by commissural interneurones
As summarized in Tables 1 and 2, EPSPs evoked from the contralateral PT were found in a smaller proportion of commissural interneurones than from the ipsilateral PT when either single maximal stimuli or trains of submaximal stimuli were used. Furthermore, these EPSPs were smaller and were more often evoked at latencies exceeding those evoked from the MLF by more than 1.6 ms, i.e. more likely trisynaptically than disynaptically. These differences were noted when the stimuli were near maximal but did not exceed (unless stated otherwise) 150 µA and therefore were likely to affect primarily, if not exclusively, fibres in only one PT, and were even more marked when weaker stimuli were tested. However, even though excitatory actions from the contralateral PT were evoked less readily, effects of stimuli applied in the ipsilateral and contralateral PT were generally similar and were enhanced when stimuli likely to encroach over the other PT (200 µA) were used. These results are thus compatible with the mediation of PT actions by RS neurones coexcited by fibres from the left and the right PT. They are also in support of the proposal that RS neurones and commissural interneurones might mediate movements that are initiated by contralateral as well as by ipsilateral PT neurones and that they provide a means for replacing the actions of PT neurones damaged on one side of the body by the actions of intact PT neurones. However, since the actions of PT neurones from one hemisphere would be weaker than normal when not assisted by the actions of PT neurones from the other hemisphere, enhancement of synaptic actions from the remaining PT fibres either pharmacologically (Jankowska et al. 2005a), or by other procedures, might be of critical importance for the recovery of motor functions. The probability of recovery will also depend on the integrity of connections between intact PT fibres and RS neurones, and between the RS neurones and commissural interneurones.
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Author's present address
A. Cabaj: Department of Neurophysiology, Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland.
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