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NEUROSCIENCE |
1 Department of Physiology, Sahlgrenska Academy, Göteborg University, 405 30 Göteborg, Sweden
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(Received 12 October 2006;
accepted after revision 18 January 2007;
first published online 25 January 2007)
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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The reasons behind considering interneurones in reflex pathways from group I and II muscle afferents as mediating uncrossed PT actions were twofold. One of these was that some crossed and uncrossed PT actions were found to be relayed by the same neurones (see the accompanying paper) and that the crossed PT actions were previously shown to be relayed by interneurones mediating reflex actions of group I and II afferents on feline motoneurones (Lundberg et al. 1962; Lundberg & Voorhoeve, 1962; Harrison & Jankowska, 1985; Davies & Edgley, 1994). At least some of these interneurones might thus contribute to the uncrossed PT actions. Another reason was that the uncrossed PT actions were found to be to a great extent relayed by ipsilaterally descending RS neurones and by interneurones that mediate disynaptic RS actions on motoneurones (see the accompanying paper, Stecina & Jankowska, 2007) and these interneurones include Ib interneurones (Takakusaki et al. 1989, 2001, 2003), interneurones in pathways from group II afferents (Lundberg et al. 1962; Davies & Edgley, 1994) and possibly also Ia interneurones (Hultborn & Udo, 1972).
The earliest disynaptic EPSPs and IPSPs following ipsilateral PT stimuli in motoneurones were evoked at latencies of 4.3–5.0 ms (Stecina & Jankowska, 2007). Interneurones mediating these PSPs should thus respond with action potentials at latencies not exceeding about 4.5 ms (taking into account some time for conduction along their axons and one synaptic delay) and EPSPs giving rise to these action potentials should be evoked at even shorter latencies. If only longer latency EPSPs were found in interneurones examined in this study, this would indicate that these interneurones might only contribute to later PT actions on motoneurones. In such a case other relay neurones would have to contribute to the earlier components.
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Methods |
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-chloralose (Rhône-Poulenc Santé, France; 5 mg kg–1; administered I.V. every 1–2 h, up to about 25 mg kg–1, and thereafter every 2–3 h up to about 55 mg kg–1). 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 experiments were terminated by a lethal dose of anaesthetic followed by formalin perfusion resulting in cardiac arrest. The effectiveness of synaptic transmission was increased by intravenous administration of 4-aminopyridine (4-AP) in doses of 0.1–0.2 mg kg–1, I.V. Atropine (0.05–0.2 mg kg–1
I.M.) and dexamethasone (1 mg kg–1
I.M.; Oradexon, Organon, Holland) were given at the beginning of the surgery in most of the experiments.
The interneurones were searched for in the lumbar 3rd to 6th (L3–L6) segments. Whenever possible interneurones were first analysed extracellularly, in particular to test their responses to stimuli applied to the lateral funiculi at the level of the thoracic 12–13 segments caudal to the contralateral hemisection. Neurones that were antidromically activated by such stimuli were eliminated from the analysis as being ascending tract cells, or long-axoned propriospinal neurones projecting outside the lumbosacral enlargement, rather than segmental interneurones. The interneurones were analysed for input from the ipsilateral and the contralateral medullary pyramidal tracts using 
150 µA (at which intensity no spread of current was previously detected to the other PT) and from several hindlimb muscle nerves (up to 5 times threshold, 5T). For the procedures of the placement, control of the current spread, and histological control of the stimulation sites, see the accompanying paper. The interneurones were investigated in two preparations: with the MLF intact or with the MLF transected at the level of caudal medulla (see Methods in the accompanying paper), in both with the spinal cord hemisected contralaterally. When the MLF was intact, indirect effects of PT stimuli might be mediated either by RS neurones with axons in the MLF or by other neurones; after transection of the MLF, by other neurones. The peripheral input was investigated in about two-thirds of these interneurones and they were classified as belonging to one of three populations using the following criteria. Interneurones classified as Ia inhibitory interneurones were located just outside the quadriceps (Q) motor nuclei at the border between the L4 and L5 segments, with input from near-threshold Q afferents. They followed stimuli applied at 400 Hz in extracellular recordings and their responses were depressed when the test stimuli were preceded by a stronger stimulation of either Q or sartorius nerves at 5–10 ms conditioning–testing intervals, compatible with effects of recurrent inhibition (see Hultborn et al. 1971). Interneurones classified as mediating reflex actions of either Ib or both Ia and Ib afferents were located within the intermediate zone at the border between the L5 and L6 segments, with short segmental latency (1.5–1.8 ms) input from group I afferents stimulated at 1.5–2T and showing typical patterns of convergence from extensor group I afferents, e.g. gastrocnemius–soleus, plantaris, flexor digitorum and halucis longus and/or quadriceps (see Eccles et al. 1957; Harrison & Jankowska, 1985). Interneurones in pathways from group II afferents were classified according to their input from group II afferents of the quadriceps and/or sartorius nerves when stimulated at 3–5T or from both group I and group II afferents of these nerves. They were located within the areas where field potentials from both group I and II afferents were evoked in the L3, L4 and L5 segments (Edgley & Jankowska, 1987; Jankowska et al. 2005b).
Analysis
Both original data and averages of 10–20 single records (with the time resolution of 30 or 40 µs per address) were stored. The latencies of the postsynaptic potentials evoked by stimulation of the PTs and the MLF were measured from the stimuli, those from the MLF being also measured from the descending volleys. They are expressed as means ± S.E.M. Differences between data sets were assessed for statistical significance by using Student's t test for paired or unpaired samples.
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Results |
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Interneurones with monosynaptic input from the ipsilateral PT
The main requirements for monosynaptically evoked EPSPs were that they were induced by single stimuli and that effects of successive stimuli in a train did not involve temporal facilitation (see Jankowska et al. 2003). With these constraints, evidence for uncrossed monosynaptic PT actions was found in only 12 interneurones. The evidence was strongest for EPSPs evoked in 8 interneurones that followed single stimuli as well as the 2nd and 3rd stimuli in a train, all at the same latencies and without temporal facilitation, as illustrated in Fig. 1A and B. In the remaining interneurones, EPSPs induced by the 2nd or 3rd stimuli were superimposed on much larger disynaptic EPSPs that were evoked at shorter latencies than those evoked by the 1st stimuli which precluded tests for temporal facilitation.
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EPSPs were classified as evoked disynaptically when they appeared only after the 2nd, 3rd or 4th stimulus in a train of ipsilateral PT stimuli and/or increased after successive stimuli (in contrast to monosynaptic EPSPs; see Jankowska et al. 2003). EPSPs fulfilling these criteria were more common than those classifiable as evoked monosynaptically. EPSPs evoked at 4.1–5 ms latencies (to the left of the 1st dotted line in Fig. 2C) were found in 13/30 and 8/14 of the interneurones in preparations in which the MLF was intact and transected, respectively. They are singled out because the range of their latencies was almost exactly that of latencies of EPSPs in motoneurones that were most reliably identified as evoked disynaptically (4.3–5 ms see Fig. 3A sample ‘a’ in Stecina & Jankowska, 2007). Longer latency EPSPs might have been evoked disynaptically or trisynaptically, although the longest ones were most likely evoked polysynaptically.
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Occlusion was demonstrated between near-maximal effects of PT and MLF stimuli. In the neurone illustrated in Fig. 3 and in two other interneurones it occurred between disynaptic EPSPs from the ipsilateral PT and monosynaptic EPSPs from the MLF because effects of the joint PT and MLF stimuli (H) were much smaller than the sum of effects of these stimuli (J) when applied separately (G and I). It showed thus that disynaptic PT actions on these neurones were to a great extent evoked via RS neurones. In five interneurones in which EPSPs were evoked by both PT and MLF stimuli, as in the interneurone illustrated in Fig. 4, the dominating effect of joint application of these stimuli was facilitation of their effects, especially when they were sub- or near-threshold. However, at higher stimulus intensities and at some critical intervals occlusion was also occurring. An example of facilitation of effects of subthreshold stimuli is shown in Fig. 5A–C. The site of the facilitation could not be decided with certainty, but the diagram in G shows that it could occur at the level of RS neurones as well as at the level of some so far unidentified spinal neurones. Facilitation at the level of RS neurones would be likely in view of indications that MLF stimuli evoke not only descending volleys and antidromic activation of RS neurones, but also synaptic excitation of either the same or other RS neurones via their medullary axon collaterals (Edgley et al. 2004; Jankowska et al. 2006).
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EPSPs evoked in the nine remaining interneurones were evoked at latencies that were much longer than latencies of EPSPs that were either monosynaptically or disynaptically evoked from the MLF. They are exemplified in Fig. 6 and represented by the data points to the right of the 2nd vertical dotted line in Fig. 2C. They might be compatible with EPSPs mediated via RS neurones that were fairly inefficiently activated by PT neurones or, more plausibly, via other neurones. However, since the latencies of disynaptic EPSPs evoked in preparations with the MLF intact and after its transection were similar (see two sets of diamonds in Fig. 2C), our results indicate that RS neurones with axons in the MLF are not the only source of even the shortest latency EPSPs (see Discussion for other possibilities).
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Given that both the corticospinal and reticulospinal tract fibres reaching lumbar segments are excitatory, any IPSPs evoked by these descending neuronal systems should be mediated by spinal inhibitory interneurones. IPSPs due to direct actions of ipsilaterally descending PT fibres on premotor inhibitory interneurones should thus be evoked disynaptically and, if they were mediated by the fastest conducting PT fibres, they might be evoked at similar latencies to disynaptic EPSPs evoked by stimulation of the MLF. In contrast, IPSPs relayed by RS neurones and inhibitory interneurones activated by them, should be evoked at least trisynaptically.
The plot of latencies of IPSPs evoked by PT stimuli in Fig. 2B shows that most of the IPSPs were evoked at the same latencies as disynaptic EPSPs and may thus represent disynaptic IPSPs relayed by direct actions of fast uncrossed PT fibres and inhibitory interneurones. However, individual data points in Fig. 2B show a continuum rather than distinct groupings, thus not allowing the separation of those evoked disynaptically and trisynaptically. In addition, in some interneurones both short and long latency IPSPs were evoked, depending on the stimulus parameters. This is illustrated in Fig. 7A–C, where longer latency IPSPs were evoked by two or three stimuli while shorter latency IPSPs appeared after the 4th stimulus. As the shortest latencies were only 1.2 ms longer than those of IPSPs evoked from the MLF, they would be compatible with trisynaptic coupling via RS neurones while the longer latency IPSPs evoked in this particular interneurone could be attributed to disynaptic actions relayed by interneurones directly activated by PT fibres.
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Comparison of synaptic actions evoked from the ipsilateral and contralateral PTs
Postsynaptic actions evoked by stimulation of the ipsilateral PT were compared with those evoked from the contralateral PT in 11 interneurones in preparations with the MLF intact and in fourteen interneurones after transection of the MLF. The comparison was made using the same number of stimuli and at the same intensities (100–150 µA). In both preparations the effects of stimulation of the contralateral PT were similar to those described above. The dominant actions were disynaptic EPSPs (Fig. 4D–F). They were found in 11 interneurones in parallel with disynaptic EPSPs from the ipsilateral PT (e.g. Fig. 2C). Monosynaptic EPSPs, like those illustrated in Fig. 1D have been found in only three interneurones.
Latencies of both the monosynaptic EPSPs and the di- or trisynaptic PSPs evoked from the contralateral PT were within the same range as PSPs from the ipsilateral PT and no statistically significant differences were found between them. The ranges were 4.9–11.3 ms for monosynaptic EPSPs and 3.9–8.9 ms for di- or trisynaptic EPSPs, as compared to 4.1–9.9 ms and 4.1–8.3 ms for monosynaptic and di- or trisynaptic EPSPs from the ipsilateral PT. For IPSPs they were 4.4–5.5 ms (mean 5.08 ± 0.33 ms) as compared to 4.2–9.6 ms (mean 5.59 ± 0.31 ms) for those evoked from the ipsilateral PT.
Mutual facilitation was as effective between actions of contralateral PT and MLF stimuli as of ipsilateral PT and MLF stimuli (see above), with an example in Fig. 5D–F. Mutual facilitation has also been found between the effects of stimuli applied within the ipsilateral and the contralateral PTs, both when the MLF was intact (in 2 neurones tested) and when it was transected (in 3 neurones tested), as exemplified in Fig. 8.
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Peripheral input was investigated in 34 of the 44 interneurones with ipsilateral PT input. These have been subdivided according to whether they were excited by the lowest or higher threshold group I afferents and/or group II afferents, or inhibited by group II afferents (Table 1). They were considered as Ia inhibitory interneurones, as interneurones mediating either inhibitory or excitatory actions of group Ia and Ib afferents, or interneurones in excitatory or inhibitory pathways from group II afferents using criteria described in the last section of Methods. Records from one of the facultative Ia interneurones are shown in Fig. 9, from Ib interneurones in Figs 7 and 8 and from group II interneurones in Figs 3 and 5.
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Discussion |
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On timing of ipsilateral PT actions relayed by spinal interneurones
PT actions on motoneurones relayed by ipsilaterally descending RS and by spinal neurones could be evoked at similar latencies only if conduction velocities of PT neurones and RS neurones were similar. Maximal conduction velocity of RS neurones was estimated to be up to 110–130 m s–1 (see, e.g. Peterson et al. 1979; Floeter et al. 1993) while PT fibres were most frequently reported to conduct at up to 60–70 m s–1 (see Porter & Lemon, 1993). However, the estimates for PT fibres were often made from conduction times over very short conduction distances (between the cortex and the medulla) and apparently without having subtracted a utilization time for the generation of action potentials by electrical stimuli (which amounts to about 0.2 ms; see Jankowska & Roberts, 1972b) from the latencies of effects of these stimuli. More reliable, therefore, are estimates of maximal conduction velocities of crossed PT fibres of about 100 m s–1, or more, that were made for distances of at least 200–300 mm (Woolsey & Chang, 1947; Brookhart & Morris, 1948; Casale & Light, 1991; Edgley et al. 1997). With respect to uncrossed PT fibres, neither their conduction velocities nor the distribution of their diameters have been reported, although examples of these fibres in the macaque spinal cord (e.g. in Fig. 4 of Lacroix et al. 2004) suggest that they may be of similar sizes, and therefore have similar maximal conduction velocity as crossed PT fibres. Our estimates of conduction velocities of uncrossed PT fibres responsible for the earliest monosynaptic EPSPs were 75–85 m s–1 (see Fig. 2A); they were lower than those of RS fibres in the MLF, but overlapped with the range of 80–88 m s–1 for crossed PT neurones targeting the same area of the spinal grey matter as determined by Casale & Light (1991).
Latencies of monosynaptic EPSPs evoked in the majority of interneurones of our sample were as long, or longer, than latencies of the earliest disynaptic EPSPs evoked in motoneurones (4.3–5 ms; see Fig. 3 in the accompanying paper). A major contribution of these interneurones to the earliest components of EPSPs evoked in motoneurones would thus seem unlikely. The ranges of latencies of monosynaptic EPSPs evoked from the ipsilateral PT (4.1–11.7 ms) and from the contralateral PT (6–11.3 ms, as found in the present study and by others) were similar. Of these, latencies of 6–8 ms of the earliest monosynaptic EPSPs evoked by stimulation of the contralateral motor cortex (Lundberg et al. 1962) would be equivalent to 5–7 ms latencies of EPSPs evoked from the medullary pyramids, given the conduction time longer by about 1 ms. They were found in interneurones with input from group II muscle afferents located in lower lumbar segments. Latencies of monosynaptic EPSPs evoked from the contralateral medullary PT in two other samples of interneurones were 4.7–6.6 ms in midlumbar interneurones (Davies & Edgley, 1994; S.A. Edgley, personal communication) and about 5.1–9.8 ms in lower lumbar interneurones (Harrison & Jankowska, 1985; see their Fig. 11). These were interneurones with input from group II and from group Ib afferents, respectively.
Latencies of disynaptic EPSPs evoked in interneurones were shorter (4.1–5.0 ms and 3.9–5.0 ms from the ipsilateral PT and the contralateral PT, respectively) but were similarly too long to allow the interneurones to mediate the earliest PT actions on motoneurones.
Which interneurones are likely to mediate the earliest actions of ipsilateral PT neurones on motoneurones?
Monosynaptic EPSPs from the ipsilateral PT were found in interneurones with input from group II muscle afferents, i.e. in the same subpopulation of interneurones in which monosynaptic EPSPs were found to be evoked from the contralateral PT (Lundberg et al. 1962; Davies & Edgley, 1994) but not in Ib interneurones in which monosynaptic input from the contralateral PT was found both previously (Harrison & Jankowska, 1985) and in one interneurone of the present study. In contrast, disynaptic EPSPs were evoked in all kinds of interneurones, indicating that all of these interneurones might mediate trisynaptic uncrossed PT actions to motoneurones. Some of these interneurones were coexcited by stimuli applied to the ipsilateral and the contralateral PT. Since the excitation from both the ipsilateral and the contralateral PT was usually disynaptic, this would be in keeping with its mediation by RS neurones coexcited by PT neurones from both hemispheres (He & Wu, 1985; Canedo & Lamas, 1993; Matsuyama & Drew, 1997; Kably & Drew, 1998). However, our data leave open the question as to which of these interneurones, other than Ia interneurones, actually acted on motoneurones as last-order premotor interneurones and whether uncrossed PT actions on inhibitory and excitatory interneurones are similar. Experiments aimed at answering this question will be reported separately.
The contribution of interneurones in reflex pathways from low threshold cutaneous afferents and from high threshold muscle, skin and joint afferents (flexor reflex afferents, FRA; Eccles & Lundberg, 1959) to the uncrossed PT actions remains another open question. It is well established that various populations of interneurones in reflex pathways from cutaneous afferents are targeted by contralateral PT neurones and they might be affected by ipsilateral PT neurones as well. However, interneurones monosynaptically excited by skin afferents are only exceptionally premotor interneurones (Fleshman et al. 1988; Hongo et al. 1989b); if they are not, they could mediate PT actions via a variety of other interneurones. Another complication is that premotor interneurones with input from cutaneous afferents are usually coexcited by muscle afferents and belong to their various categories (e.g. Ib interneurones, Harrison & Jankowska, 1985; or group II interneurones, Edgley & Jankowska, 1987). This may also be true for last-order FRA interneurones and for interneurones in which only cutaneous peripheral input was investigated (Hongo et al. 1989a,b).
With respect to other spinal neurones that might mediate uncrossed PT actions on motoneurones, of particular interest are two populations of propriospinal neurones. One of these are propriospinal neurones located between the C4 and Th2 segments. They were found to evoke monosynaptic EPSPs in hindlimb motoneurones and in view of their high conduction velocity, estimated to be about 100 m s–1 (Jankowska et al. 1973, 1974), they could mediate disynaptic PT actions as effectively and as quickly as RS neurones. However, sources of input to these neurones, in particular from uncrossed PT fibres, have not been investigated. Another population to consider are propriospinal neurones located in the C3–C5 segments, with potent input from a number of descending tract neurones and axons traced as far caudally as the lumbar segments (Illert et al. 1978; Alstermark et al. 1991). These were found to conduct at 62–124 m s–1 (Alstermark et al. 1991), i.e. within the required range of conduction velocities, but uncrossed PT actions on these neurones were not investigated and monosynaptic actions from the contralateral PT were reported to be fairly weak and were found in only a small proportion of these cells (Alstermark et al. 1987). Some of these neurones might belong to the population of the fast conducting propriospinal neurones described by Jankowska et al. (1973, 1974) but it has not been established whether they project more caudally than the L3–L5 segments, nor whether they have direct actions on motoneurones or premotor interneurones.
On networks of neurones mediating actions of ipsilateral PT neurones and their contribution to centrally initiated movements
Generally weak actions of stimuli applied in the ipsilateral PT on interneurones investigated in this study raise the question of whether these interneurones could contribute to ipsilateral PT actions in any essential way. The question is difficult to answer but estimating the role played by these interneurones, one should take into account that the effectiveness of their activation by uncrossed PT fibres ought to be higher under natural conditions than in reduced, anaesthetized preparations in which a great part of the input to the interneurones is eliminated. By leaving intact only the ipsilateral half of the spinal cord we deprived the interneurones of a considerable amount of background descending excitatory actions, including any evoked via collaterals of contralaterally descending corticospinal tract fibres (for review see Martin, 2005), or reticulospinal fibres (Matsuyama et al. 1993, 1999) and commissural interneurones activated by these fibres (Jankowska et al. 2005c; Cabaj et al. 2006). Additional lesions of the ipsilateral MLF further aggravated this situation. On the other hand, partial denervation of the hindlimbs and immobilization reduced input from the periphery. One should also consider that the state of the interneurones has deteriorated soon after their penetration (with an example in Fig. 9) and that both monosynaptically and disynaptically evoked EPSPs were originally larger than those illustrated. Thus even if the actions of uncrossed PT fibres on premotor interneurones of our sample were weaker than other synaptic actions, nerve impulses in PT fibres might activate these interneurones by acting on the top of other synaptic actions.
With respect to the disynaptic actions of ipsilateral PT neurones on interneurones, our results suggest that they are evoked similarly on motoneurones and, as indicated in Fig. 10, are collateral to actions on motoneurones, including actions of RS neurones and of currently unidentified ipsilaterally located spinal neurones. However, disynaptic collateral actions of interneurones of the populations analysed in this study would be unlikely because latencies of both monosynaptic and disynaptic excitation of these neurones were generally longer than those of the earliest actions of PT neurones on motoneurones.
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Mediation of PT actions via several parallel channels appears to be well suited for securing these actions by their joint activation. Because of different conduction velocities and transfer delays in the various pathways, nerve impulses initiated in even the fastest conducting PT neurones will reach motoneurones over a time period of several milliseconds rather than synchronously. As indicated in Table 1, the latencies of monosynaptic and di- or trisynaptic uncrossed PT actions span between 4 and more than 9 ms and the range of latencies of double crossed trisynaptic PT actions evoked via contralateral RS neurones and commissural interneurones is similar (4–7 ms; Jankowska et al. 2005a). Actions mediated by these four pathways may be further strengthened by neurones providing positive feedback and/or feed-forward input to their constituent neurones. For instance, activation of RS neurones by direct actions of PT fibres is followed by their re-activation via other medullary neurones excited by axon collaterals of RS neurones or other neurones, as found previously both under our experimental conditions (Fig. 1C in Edgley et al. 2004; Fig. 6 in Jankowska et al. 2006) and in other studies. Delayed activation of RS neurones would result in even more delayed activation of commissural interneurones and additional spinal interneurones which are in turn activated by them (Jankowska et al. 2005c; Cabaj et al. 2006). It may thus further strengthen and prolong their effects on motoneurones.
Strengthening and prolonging the earliest PT actions on motoneurones by even as little as 5–10 ms might play a role in triggering voltage-dependent persistent inward current and plateau potentials (Schwindt & Crill, 1980; Hounsgaard et al. 1988; Hultborn, 1999, 2003) and thereby for inducing sustained discharges required for tonic voluntary movements by relatively short lasting corticospinal commands. The critical level of depolarization needed for the persistent inward current has been defined but the critical duration of synaptic actions needed to reach such level of depolarization has apparently not. On the basis of published records it appears to be at least some 10 ms (see Fig. 6C and E in Schwindt & Crill, 1980). A delay of 20–40 ms appears to have been involved when plateau potentials and tonic discharges of a motoneurone were evoked by stimulation of corticospinal tract fibres (Fig. 4 in Hultborn et al. 2003), but it exceeded 100 ms (Fig. 1 in Lee & Heckman, 1996) when they were induced by muscle vibration. A similar range of delays in the appearance of plateau potentials was found in extensor motoneurones by stimulation of group I afferents during the extension phase of fictive locomotor activity in decerebrate cats (D. McCrea, personal communication). Doubling or tripling of the period of depolarization evoked in motoneurones by PT actions via several pathways with different overall conduction times might thus add to other mechanisms ensuring sustained motoneuronal responses (for references see Lundberg et al. 1987; Li et al. 2006).
Despite their importance, not all of the available parallel pathways would be needed to allow PT neurones to act on ipsilateral motoneurones. It has been demonstrated that under favourable conditions, ipsilateral PT actions may be mediated by RS relays alone. For double crossed pathways this was shown by a negligible effect of lesions of both the right and left corticospinal tract fibres running within the dorsolateral funiculus (DLF) on the trisynaptic actions of PT neurones on motoneurones evoked via commissural interneurones (see Fig. 4 in Edgley et al. 2004). Since the lesions were made at a C2–C3 level, they eliminated the effects of PT fibres on both segmental interneurones and propriospinal neurones located caudal to the C3 segment. These lesions also had negligible effects on uncrossed disynaptic PT actions on ipsilateral motoneurones evoked via RS fibres descending within the ipsilateral MLF (see Fig. 4 in Edgley et al. 2004 and Fig. 3C and D in Jankowska & Edgley, 2006), especially when synaptic transmission was enhanced by 4-AP (Jankowska et al. 2005a). Another case of actions evoked by stimulation of the motor cortex after transection of medullary pyramids was reported by Hongo & Jankowska (1967). They found that monosynaptic reflexes were then facilitated under chloralose anaesthesia but not after an additional small dose of pentobarbital that weakens the activation of RS neurones by PT neurones, nor after lesions of deeper parts of the lateral funiculus including reticulospinal tract fibres. The facilitation was evoked from both the contralateral and the ipsilateral motor cortex (see Fig. 4 in Hongo & Jankowska, 1967).
Corticospinal actions might also be evoked without involving RS relays. This was indicated by the disappearance of facilitation of Ia reciprocal inhibition by crossed PT fibres after transection of the contralateral pyramid in preparations under pentobarbital anaesthesia (Lundberg & Voorhoeve, 1962), showing that the facilitation depended critically on PT fibres running within the caudal part of the medulla.
The neuronal organization of pathways between PT neurones and ipsilateral motoneurones summarized in Fig. 10 would be of importance not only for strengthening and prolonging PT actions on motoneurones, but also for gating actions evoked by PT neurones at the level of relay neurones in these various pathways. As shown repeatedly, e.g. by Drew and colleagues (Drew & Rossignol, 1990; Drew, 1991; Drew et al. 2002) and Fetz and colleagues (Fetz et al. 2000, 2002) the actions of both corticospinal and reticulospinal neurones are intricately linked to the patterned activity of spinal neuronal networks, in particular during movements requiring their proper coordination. Shaping of various patterns of movements may thus require a highly plastic use of spinal networks, involving both excitation and inhibition of relay neurones in these networks.
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References |
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Alstermark B, Lundberg A, Pinter M & Sasaki S (1987). Subpopulations and functions of long C3–C5 propriospinal neurones. Brain Res 404, 395–400.[CrossRef][Medline]
Brookhart JM & Morris RE (1948). Antidromic potential recordings from the bulbar pyramid of the cat. J Neurophysiol 11, 387–398.
Cabaj A, Stecina K & Jankowska E (2006). Same spinal interneurons mediate reflex actions of group Ib and II afferents and crossed reticulospinal actions. J Neurophysiol 95, 3911–3922.
Canedo A & Lamas JA (1993). Pyramidal and corticospinal synaptic effects over reticulospinal neurones in the cat. J Physiol 463, 475–489.
Casale EJ & Light AR (1991). The terminations of single, physiologically identified, somatosensory, corticospinal tract axons in the lumbar spinal cord of the cat. J Neurophysiol 66, 1738–1749.
Casale EJ, Light AR & Rustioni A (1988). Direct projection of the corticospinal tract to the superficial laminae of the spinal cord in the rat. J Comp Neurol 278, 275–286.[CrossRef][Medline]
Davies HE & Edgley SA (1994). Inputs to group II-activated midlumbar interneurones from descending motor pathways in the cat. J Physiol 479, 463–473.[Medline]
Drew T (1991). Functional organization within the medullary reticular formation of the intact unanesthetized cat. III. Microstimulation during locomotion. J Neurophysiol 66, 919–938.
Drew T, Jiang W & Widajewicz W (2002). Contributions of the motor cortex to the control of the hindlimbs during locomotion in the cat. Brain Res Rev 40, 178–191.[CrossRef][Medline]
Drew T & Rossignol S (1990). Functional organization within the medullary reticular formation of intact unanesthetized cat. II. Electromyographic activity evoked by microstimulation. J Neurophysiol 64, 782–795.
Dum RP & Strick PL (1996). Spinal cord terminations of the medial wall motor areas in macaque monkeys. J Neurosci 16, 6513–6525.
Eccles JC, Eccles RM & Lundberg A (1957). Synaptic actions in motoneurones caused by impulses in Golgi tendon afferents. J Physiol 138, 227–252.
Eccles R & Lundberg A (1959). Synaptic actions in motoneurones by afferents which may evoke the flexion reflex. Arch Ital Biol 97, 199–221.
Edgley SA, Eyre JA, Lemon RN & Miller S (1997). Comparison of activation of corticospinal neurons and spinal motor neurons by magnetic and electrical transcranial stimulation in the lumbosacral cord of the anaesthetized monkey. Brain 120, 839–853.
Edgley SA & Jankowska E (1987). An interneuronal relay for group I and II muscle afferents in the midlumbar segments of the cat spinal cord. J Physiol 389, 647–674.
Edgley SA, Jankowska E & Hammar I (2004). Ipsilateral actions of feline corticospinal tract neurons on limb motoneurons. J Neurosci 24, 7804–7813.
Fetz EE, Perlmutter SI & Prut Y (2000). Functions of mammalian spinal interneurons during movement. Curr Opin Neurobiol 10, 699–707.[CrossRef][Medline]
Fetz EE, Perlmutter SI, Prut Y, Seki K & Votaw S (2002). Roles of primate spinal interneurons in preparation and execution of voluntary hand movement. Brain Res Rev 40, 53–65.[CrossRef][Medline]
Fleshman JW, Rudomin P & Burke RE (1988). Supraspinal control of a short-latency cutaneous pathway to hindlimb motoneurons. Exp Brain Res 69, 449–459.[Medline]
Floeter MK, Sholomenko GN, Gossard JP & Burke RE (1993). Disynaptic excitation from the medial longitudinal fasciculus to lumbosacral motoneurons: modulation by repetitive activation, descending pathways, and locomotion. Exp Brain Res 92, 407–419.[Medline]
Harrison PJ & Jankowska E (1985). Sources of input to interneurones mediating group I non-reciprocal inhibition of motoneurones in the cat. J Physiol 361, 379–401.
He XW & Wu CP (1985). Connections between pericruciate cortex and the medullary reticulospinal neurons in cat: an electrophysiological study. Exp Brain Res 61, 109–116.[Medline]
Hongo T & Jankowska E (1967). Effects from the sensorimotor cortex on the spinal cord in cats with transected pyramids. Exp Brain Res 3, 117–134.[Medline]
Hongo T, Kitazawa S, Ohki Y, Sasaki M & Xi MC (1989a). A physiological and morphological study of premotor interneurones in the cutaneous reflex pathways in cats. Brain Res 505, 163–166.[CrossRef][Medline]
Hongo T, Kitazawa S, Ohki Y & Xi MC (1989b). Functional identification of last-order interneurones of skin reflex pathways in the cat forelimb segments. Brain Res 505, 167–170.[CrossRef][Medline]
Hounsgaard J, Hultborn H, Jespersen B & Kiehn O (1988). Bistability of -motoneurones in the decerebrate cat and in the acute spinal cat after intravenous 5-hydroxytryptophan. J Physiol 405, 345–367.
Hultborn H (1999). Plateau potentials and their role in regulating motoneuronal firing. Prog Brain Res 123, 39–48.[Medline]
Hultborn H, Denton ME, Wienecke J & Nielsen JB (2003). Variable amplification of synaptic input to cat spinal motoneurones by dendritic persistent inward current. J Physiol 552, 945–952.
Hultborn H, Jankowska E & Lindstrom S (1971). Recurrent inhibition of interneurones monosynaptically activated from group Ia afferents. J Physiol 215, 613–636.
Hultborn H & Udo M (1972). Convergence in the reciprocal Ia inhibitory pathway of excitation from descending pathways and inhibition from motor axon collaterals. Acta Physiol Scand 84, 95–108.[Medline]
Illert M, Lundberg A, Padel Y & Tanaka R (1978). Integration in descending motor pathways controlling the forelimb in the cat. 5. Properties of and monosynaptic excitatory convergence on C3–C4 propriospinal neurones. Exp Brain Res 33, 101–130.[Medline]
Jankowska E, Cabaj A & Pettersson LG (2005a). How to enhance ipsilateral actions of pyramidal tract neurons. J Neurosci 25, 7401–7405.
Jankowska E & Edgley SA (2006). How can corticospinal tract neurons contribute to ipsilateral movements? A question with implications for recovery of motor functions. Neuroscientist 12, 67–79.
Jankowska E, Edgley SA, Krutki P & Hammar I (2005b). Functional differentiation and organization of feline midlumbar commissural interneurones. J Physiol 565, 645–658.
Jankowska E, Hammar I, Slawinska U, Maleszak K & Edgley SA (2003). Neuronal basis of crossed actions from the reticular formation upon feline hindlimb motoneurons. J Neurosci 23, 1867–1878.
Jankowska E, Krutki P & Matsuyama K (2005c). Relative contribution of Ia inhibitory interneurones to inhibition of feline contralateral motoneurones evoked via commissural interneurones. J Physiol 568, 617–628.
Jankowska E, Lundberg A, Roberts WJ & Stuart D (1974). A long propriospinal system with direct effect on motoneurones and on interneurones in the cat lumbosacral cord. Exp Brain Res 21, 169–194.[Medline]
Jankowska E, Lundberg A & Stuart D (1973). Propriospinal control of last order interneurones of spinal reflex pathways in the cat. Brain Res 53, 227–231.[CrossRef][Medline]
Jankowska E & Roberts W (1972a). Synaptic actions of single interneurones mediating reciprocal Ia inhibition of motoneurones. J Physiol 222, 623–642.
Jankowska E & Roberts WJ (1972b). An electrophysiological demonstration of the axonal projections of single spinal interneurones in the cat. J Physiol 222, 597–622.
Jankowska E, Stecina K, Cabaj A, Pettersson L-G & Edgley SA (2006). Neuronal relays in double-crossed pathways between feline motor cortex and ipsilateral hindlimb motoneurons. J Physiol 575, 527–541.
Kably B & Drew T (1998). Corticoreticular pathways in the cat. I. Projection patterns and collaterization. J Neurophysiol 80, 389–405.
Lacroix S, Havton LA, McKay H, Yang H, Brant A, Roberts J et al. (2004). Bilateral corticospinal projections arise from each motor cortex in the macaque monkey: a quantitative study. J Comp Neurol 473, 147–161.[CrossRef][Medline]
Lee RH & Heckman CJ (1996). Influence of voltage-sensitive dendritic conductances on bistable firing and effective synaptic current in cat spinal motoneurons in vivo. J Neurophysiol 76, 2107–2110.
Li WC, Soffe SR, Wolf E & Roberts A (2006). Persistent responses to brief stimuli: feedback excitation among brainstem neurons. J Neurosci 26, 4026–4035.
Lundberg A, Malmgren K & Schomburg ED (1987). Reflex pathways from group II muscle afferents. 3. Secondary spindle afferents and the FRA: a new hypothesis. Exp Brain Res 65, 294–306.[Medline]
Lundberg A, Norrsell U & Voorhoeve P (1962). Pyramidal effects on lumbo-sacral interneurones activated by somatic afferents. Acta Physiol Scand 56, 220–229.[Medline]
Lundberg A & Voorhoeve P (1962). Effects from the pyramidal tract on spinal reflex arcs. Acta Physiol Scand 56, 201–219.[Medline]
Martin JH (2005). The corticospinal system: from development to motor control. Neuroscientist 11, 161–173.[Abstract]
Matsuyama K & Drew T (1997). Organization of the projections from the pericruciate cortex to the pontomedullary brainstem of the cat: a study using the anterograde tracer Phaseolus vulgaris-leucoagglutinin. J Comp Neurol 389, 617–641.[CrossRef][Medline]
Matsuyama K, Kobayashi Y, Takakusaki K, Mori S & Kimura H (1993). Termination mode and branching patterns of reticuloreticular and reticulospinal fibers of the nucleus reticularis pontis oralis in the cat: an anterograde PHA-L tracing study. Neurosci Res 17, 9–21.[CrossRef][Medline]
Matsuyama K, Mori F, Kuze B & Mori S (1999). Morphology of single pontine reticulospinal axons in the lumbar enlargement of the cat: a study using the anterograde tracer PHA-L. J Comp Neurol 410, 413–430.[CrossRef][Medline]
Peterson BW, Pitts NG & Fukushima K (1979). Reticulospinal connections with limb and axial motoneurons. Exp Brain Res 36, 1–20.[CrossRef][Medline]
Porter R & Lemon RN (1993). Corticospinal Function and Voluntary Movement. Clarendon Press, Oxford.
Rexed B (1954). A cytoarchitectonic atlas of the spinal cord in the cat. J Comp Neurol 100, 297–379.[CrossRef][Medline]
Schwindt PC & Crill WE (1980). Properties of a persistent inward current in normal and TEA-injected motoneurons. J Neurophysiol 43, 1700–1724.
Stecina K & Jankowska E (2007). Uncrossed actions of feline corticospinal tract neurones on hindlimb motoneurones evoked via ipsilaterally descending pathways. J Physiol 580, 119–132.
Takakusaki K, Kohyama J & Matsuyama K (2003). Medullary reticulospinal tract mediating a generalized motor inhibition in cats. III. Functional organization of spinal interneurons in the lower lumbar segments. Neuroscience 121, 731–746.[CrossRef][Medline]
Takakusaki K, Kohyama J, Matsuyama K & Mori S (2001). Medullary reticulospinal tract mediating the generalized motor inhibition in cats: parallel inhibitory mechanisms acting on motoneurons and on interneuronal transmission in reflex pathways. Neuroscience 103, 511–527.[CrossRef]
