J S Riddell

Publications of J S Riddell

• P boutons in lamina IX of the rodent spinal cord express high levels of glutamic acid decarboxylase-65 and originate from cells in deep medial dorsal horn.

  Authors: D I Hughes, M Mackie, G G Nagy, J S Riddell, D J Maxwell, G Szabó, F Erdélyi, G Veress, P Szucs, M Antal, A J Todd

  Proceedings of the National Academy of Sciences of the United States of America. 07/2005; 102(25):9038-43.

  Presynaptic inhibition of primary muscle spindle (group Ia) afferent terminals in motor nuclei of the spinal cord plays an important role in regulating motor output and is produced by a population ofPresynaptic inhibition of primary muscle spindle (group Ia) afferent terminals in motor nuclei of the spinal cord plays an important role in regulating motor output and is produced by a population of GABAergic axon terminals known as P boutons. Despite extensive investigation, the cells that mediate this control have not yet been identified. In this work, we use immunocytochemistry with confocal microscopy and EM to demonstrate that P boutons can be distinguished from other GABAergic terminals in the ventral horn of rat and mouse spinal cord by their high level of the glutamic acid decarboxylase (GAD) 65 isoform of GAD. By carrying out retrograde labeling from lamina IX in mice that express green fluorescent protein under the control of the GAD65 promoter, we provide evidence that the cells of origin of the P boutons are located in the medial part of laminae V and VI. Our results suggest that P boutons represent the major output of these cells within the ventral horn and are consistent with the view that presynaptic inhibition of proprioceptive afferents is mediated by specific populations of interneurons. They also provide a means of identifying P boutons that will be important in studies of the organization of presynaptic control of Ia afferents.

• Lack of evidence for significant neuronal loss in laminae I-III of the spinal dorsal horn of the rat in the chronic constriction injury model.

  Authors: E Polgár, S Gray, J S Riddell, A J Todd

  Pain. 10/2004; 111(1-2):144-50.

  Peripheral nerve injury leads to structural and functional changes in the spinal dorsal horn, and these are thought to be involved in the development of neuropathic pain. In the chronic constrictionPeripheral nerve injury leads to structural and functional changes in the spinal dorsal horn, and these are thought to be involved in the development of neuropathic pain. In the chronic constriction injury (CCI) model, abnormal 'dark' neurons and apoptotic nuclei have been observed in laminae I-III of the dorsal horn in the territory innervated by the injured sciatic nerve. These findings have been taken as evidence that there is significant neuronal death in this model, and it has been suggested that loss of inhibition resulting from death of GABAergic inhibitory interneurons contributes to the neuropathic pain. However, loss of neurons from the dorsal horn has not been directly demonstrated in neuropathic models, even though this issue is of considerable importance for our understanding of the mechanisms that underlie neuropathic pain. In this study, we have looked for evidence of neuronal death by using a stereological method (the optical disector) with NeuN-immunostaining, and examining spinal cords of naïve rats, and of rats that had undergone CCI or sham operations. All of the CCI animals showed clear signs of thermal hyperalgesia. However, the numbers of neurons in laminae I-III of the ipsilateral dorsal horn in these animals did not differ significantly from those on the contralateral side, nor from those of sham-operated or naïve animals. These results do not, therefore, support the suggestion that there is significant neuronal death in the dorsal horn in this model.

• Selective loss of spinal GABAergic or glycinergic neurons is not necessary for development of thermal hyperalgesia in the chronic constriction injury model of neuropathic pain.

  Authors: E Polgár, D I Hughes, J S Riddell, D J Maxwell, Z Puskár, A J Todd

  Pain. 08/2003; 104(1-2):229-39.

  GABA and glycine are inhibitory neurotransmitters used by many neurons in the spinal dorsal horn, and intrathecal administration of GABA(A) and glycine receptor antagonists produces behavioural signsGABA and glycine are inhibitory neurotransmitters used by many neurons in the spinal dorsal horn, and intrathecal administration of GABA(A) and glycine receptor antagonists produces behavioural signs of allodynia, suggesting that these transmitters have an important role in spinal pain mechanisms. Several studies have described a substantial loss of GABA-immunoreactive neurons from the dorsal horn in nerve injury models, and it has been suggested that this may be associated with a loss of inhibition, which contributes to the behavioural signs of neuropathic pain. We have carried out a quantitative stereological analysis of the proportions of neurons in laminae I, II and III of the rat dorsal horn that show GABA- and/or glycine-immunoreactivity 2 weeks after nerve ligation in the chronic constriction injury (CCI) model, as well as in sham-operated and nai;ve animals. At this time, rats that had undergone CCI showed a significant reduction in the latency of withdrawal of the ipsilateral hindpaw to a radiant heat stimulus, suggesting that thermal hyperalgesia had developed. However, we did not observe any change in the proportion of neurons in laminae I-III of the ipsilateral dorsal horn that showed GABA- or glycine-immunoreactivity compared to the contralateral side in these animals, and these proportions did not differ significantly from those seen in sham-operated or nai;ve animals. In addition, we did not see any evidence for alterations of GABA- or glycine-immunostaining in the neuropil of laminae I-III in the animals that had undergone CCI. Our results suggest that significant loss of GABAergic or glycinergic neurons is not necessary for the development of thermal hyperalgesia in the CCI model of neuropathic pain.

• Serotoninergic and noradrenergic axonal contacts associated with premotor interneurons in spinal pathways from group II muscle afferents.

  Authors: D J Maxwell, J S Riddell, E Jankowska

  The European journal of neuroscience. 05/2000; 12(4):1271-80.

  We investigated the possibility that monoaminergic axons make contacts with spinal interneurons which project to motor nuclei and are monosynaptically activated by group II muscle afferents.We investigated the possibility that monoaminergic axons make contacts with spinal interneurons which project to motor nuclei and are monosynaptically activated by group II muscle afferents. Interneurons in midlumbar spinal segments of adult cats were characterized electrophysiologically and intracellularly labelled with tetramethylrhodamine dextran. Serotoninergic and noradrenergic axons were identified with immunofluorescence in sections containing labelled cells. Contacts between monoaminergic axons and interneurons were investigated with three-colour confocal laser scanning microscopy and analysed with a computer reconstruction program. Cell bodies and dendritic trees of five cells were reconstructed and putative contacts were plotted. The average number of contacts formed by serotoninergic axons was 140 and the average number of noradrenergic contacts was 38. The majority (95%) of contacts were formed with dendrites; these were distributed over the entire dendritic tree, even on the most distal branches. These findings provide a morphological basis for the modulatory actions of monoamines on premotor spinal interneurons in pathways from group II muscle afferents.

• Interneurones in pathways from group II muscle afferents in the lower-lumbar segments of the feline spinal cord.

  Authors: J S Riddell, M Hadian

  The Journal of physiology. 01/2000; 522 Pt 1:109-23.

  Interneurones receiving excitatory input from group II muscle afferents of hindlimb nerves and located in the lower-lumbar (L6-L7) segments of the cat spinal cord were investigated using bothInterneurones receiving excitatory input from group II muscle afferents of hindlimb nerves and located in the lower-lumbar (L6-L7) segments of the cat spinal cord were investigated using both extracellular and intracellular recording. The interneurones were located mainly in the lateral parts of laminae IV-VII, dorsal and lateral to the main region in which interneurones with input from group I muscle afferents are located. Almost half the sample of interneurones (38 of 76) were characterized by an ipsilateral ascending projection within the lateral funiculus to the L4 level. The most powerful group II excitation was produced by afferents of the quadriceps and deep peroneal muscle nerves (which discharged 70-80% of extracellularly recorded neurones) while group II afferents of tibialis posterior, posterior biceps-semitendinosus and gastrocnemius soleus were also highly effective (discharging 45-55% of extracellularly recorded neurones). A proportion of intracellularly recorded group II EPSPs were monosynaptic. Seventy-five per cent of the extracellularly recorded interneurones were discharged by group II afferents of two or more muscle nerves and 43% by afferents of three or more nerves. Group I muscle afferents evoked small EPSPs in over one-quarter of the intracellularly recorded interneurones and virtually all were strongly excited by cutaneous afferents. Evidence of excitatory input from joint, interosseous and group III muscle afferents was also observed. The properties of the interneurones are compared with those of others in the lumbosacral segments and the possibility that they may function as last-order premotor interneurones is discussed.

• Field potentials generated by group II muscle afferents in the lower-lumbar segments of the feline spinal cord.

  Authors: J S Riddell, M Hadian

  The Journal of physiology. 01/2000; 522 Pt 1:97-108.

  The actions of group II muscle afferents projecting to the lower-lumbar (L6 and L7) segments of the cat spinal cord were investigated by recording the cord dorsum and focal synaptic field potentialsThe actions of group II muscle afferents projecting to the lower-lumbar (L6 and L7) segments of the cat spinal cord were investigated by recording the cord dorsum and focal synaptic field potentials evoked by electrical stimulation of hindlimb muscle nerves. Cord dorsum potentials recorded over the lower-lumbar segments were generally much smaller than those produced by group II afferents terminating within the midlumbar and sacral segments. Only group II afferents of tibialis posterior produced potentials with an amplitude (mean maximal amplitude 39 microV, n = 7) approaching that of potentials over other segments. Focal synaptic potentials (mean maximal amplitudes 135-200 microV) were evoked by group II afferents of the following muscle nerves, listed in order of effectiveness: quadriceps, tibialis posterior (throughout L6 and L7), gastrocnemius soleus, flexor digitorum longus, posterior biceps-semitendinosus and popliteus (mainly within L7). Field potentials were recorded in the dorsal horn (laminae IV-V) and also more ventrally in a region which included the lateral part of the intermediate zone (lateral to the large group I intermediate field potentials) and often extended into the ventral horn (laminae V-VII). The latencies of the group II potentials are considered compatible with the monosynaptic actions of the fastest conducting group II muscle afferents. The results are compared with morphological evidence on the pattern of termination of group II muscle afferents in the lower-lumbar segments and with previous descriptions of the actions of group II muscle afferents in midlumbar and sacral segments.

• Axoaxonic synapses on terminals of group II muscle spindle afferent axons in the spinal cord of the cat.

  Authors: D J Maxwell, J S Riddell

  The European journal of neuroscience. 07/1999; 11(6):2151-9.

  The purpose of the present study was to determine if terminals of identified group II muscle spindle afferents participate in axoaxonic synaptic arrangements and, if so, to investigate theThe purpose of the present study was to determine if terminals of identified group II muscle spindle afferents participate in axoaxonic synaptic arrangements and, if so, to investigate the transmitter content of presynaptic terminals in these arrangements. Group II muscle afferents supplying the gastrocnemius-soleus or semitendinosus muscles were identified in adult cats and stained intra-axonally with horseradish peroxidase. In total, three group II axons were labelled and processed for combined light and electron microscopy. Group II axons gave rise to collaterals which characteristically descended through the superficial dorsal horn and formed relatively sparse terminal arborizations in the dorsal horn (laminae IV and V) and more profuse arbors in the intermediate grey matter (laminae VI-VII). Forty boutons were examined through series of ultrathin sections and all but four were postsynaptic to other axon terminals. Occasionally, more than one axon was presynaptic to a single group II terminal. Immunogold studies showed that all axons in presynaptic apposition to group II boutons contained gamma-aminobutyric acid (GABA) and also that glycine was colocalized in the majority of these axons. This evidence suggests that transmission from group II muscle afferents is under strong presynaptic inhibitory control and that it is mainly the subgroup of GABAergic interneurons with colocalized glycine which mediate this inhibition. Seventeen group II boutons were components of synaptic triads where the presynaptic axoaxonic bouton formed a synapse with the same dendrite as the group II axon. Therefore, a proportion of the interneurons which form axoaxonic synapses with group II axons are also likely to have postsynaptic inhibitory actions on target neurons of group II afferents.

• Topographical organization of group II afferent input in the rat spinal cord.

  Authors: J S Riddell, M Hadian

  The Journal of comparative neurology. 06/1998; 394(3):357-73.

  The organization of neurons in the lumbar enlargement of the rat spinal cord processing information conveyed by group II afferents of hind-limb muscle nerves has been investigated by using cordThe organization of neurons in the lumbar enlargement of the rat spinal cord processing information conveyed by group II afferents of hind-limb muscle nerves has been investigated by using cord dorsum and intraspinal field potential recording. Group II afferents of different muscle nerves were found to evoke their strongest synaptic actions in specific segments of the lumbar cord. Group II afferents of quadriceps and deep peroneal nerves evoked potentials mainly at the rostral end of the lumbar enlargement (L1-rostral L3), whereas group II afferents of gastrocnemius-soleus and hamstring nerves evoked their main synaptic actions at the caudal end of the lumbar enlargement (L5). In the central lumbar segments (caudal L3-L4), the largest group II potentials were produced by afferents of tibialis posterior and, to a lesser degree, flexor digitorum longus. Field potentials evoked by group II afferents of quadriceps, tibialis posterior, and flexor digitorum longus were largest in the dorsal horn (up to 600 microV), but also occurred in the ventral horn where they were sometimes preceded by group I field potentials. In contrast, field potentials evoked by group II afferents of gastrocnemius-soleus and hamstring nerves were restricted to the dorsal horn. These results indicate that neurons in different segments of the rat lumbar spinal cord process information from group II afferents of different hind-limb muscles. Furthermore, the topographical organization of group II neuronal systems in the rat is similar in several respects to that in the cat and may therefore represent a general organizational feature of the mammalian spinal cord.

• Synaptic connections of dorsal horn group II spinal interneurons: synapses formed with the interneurons and by their axon collaterals.

  Authors: D J Maxwell, R Kerr, E Jankowska, J S Riddell

  The Journal of comparative neurology. 04/1997; 380(1):51-69.

  Five dorsal horn interneurons with monosynaptic input from group II primary afferent fibres were physiologically characterized and intracellularly labelled with horseradish peroxidase. The cells wereFive dorsal horn interneurons with monosynaptic input from group II primary afferent fibres were physiologically characterized and intracellularly labelled with horseradish peroxidase. The cells were prepared for combined light and electron microscopy, and synaptic arrangements formed by axon collaterals of interneurons and synapses formed with their dendrites and somata were examined with the electron microscope. Immunogold reactions for gamma-aminobutyric acid, glycine and glutamate were performed to determine if these synapses were excitatory or inhibitory. Axon collaterals in lamina VI formed synapses with somata and dendrites of other neurons, and collaterals of one cell also formed axoaxonic synapses. It was concluded that one cell from the sample was inhibitory, whereas the remainder were probably excitatory. Dendrites and cell bodies of interneurons were contacted by several types of synaptic bouton. The first type of bouton displayed immunoreactivity for glutamate, the second type contained both gamma-aminobutyric acid and glycine, the third type contained glycine alone, and the fourth type contained gamma-aminobutyric acid alone. Some large glutamatergic boutons were postsynaptic to other boutons. Presynaptic boutons at these axoaxonic synapses always contained gamma-aminobutyric acid but a minority also contained glycine. The results of this study demonstrate the heterogeneity of dorsal horn group II interneurons and provide evidence that they include inhibitory and probably also excitatory neurons. Boutons originating from several chemically different classes of neuron are responsible for postsynaptic inhibition of these interneurons, and the presence of axoaxonic synapses indicates that their excitatory input is also controlled presynaptically.

• How effective is integration of information from muscle afferents in spinal pathways?

  Authors: E Jankowska, E V Perfilieva, J S Riddell

  Neuroreport. 11/1996; 7(14):2337-40.

  Integration of information forwarded by group I and group II muscle afferents to premotor interneurones was estimated from spatial facilitation in oligosynaptic (most likely disynaptic) reflexIntegration of information forwarded by group I and group II muscle afferents to premotor interneurones was estimated from spatial facilitation in oligosynaptic (most likely disynaptic) reflex pathways from these afferents. Indications for mutual facilitation of synaptic actions of group I and group II afferents have been found on both inhibitory and excitatory premotor interneurones but were easier to demonstrate in the inhibitory pathways. However, the facilitation appeared weak under our experimental conditions and depended critically upon the intensity and timing of the stimuli used to activate muscle afferents.

• Organization of neuronal systems mediating presynaptic inhibition of group II muscle afferents in the cat.

  Authors: J S Riddell, E Jankowska, J Huber

  The Journal of physiology. 04/1995; 483 ( Pt 2):443-60.

  1. The organization of neuronal systems mediating presynaptic control of transmission from group II muscle afferent fibres has been investigated by comparing the sources of presynaptic inhibition of1. The organization of neuronal systems mediating presynaptic control of transmission from group II muscle afferent fibres has been investigated by comparing the sources of presynaptic inhibition of fibres terminating in different segments of the spinal cord: fibres of the semitendinosus and lateral gastrocnemius muscle nerves terminating in the sacral segments and of the tibialis anterior and extensor digitorum longus muscle nerves terminating in the midlumbar segments. 2. Two measures of presynaptic inhibition were used: depolarization of the terminals of group II fibres (detected as changes in the excitability of single fibres to electrical stimuli) and a decrease in the effectiveness of their synaptic actions (detected as a decrease in the amplitude of monosynaptic field potentials evoked by group II muscle afferents). 3. Group II muscle afferents strongly depolarized all of the group II afferent fibres, while group I muscle afferents contributed to the depolarization of only a few. The majority of fibres were as effectively depolarized by cutaneous afferents as by the most effective muscle afferents. However, the effectiveness with which afferents of different nerves depolarized group II muscle afferent fibres in the sacral and midlumbar segments differed. The most effective afferents were those of nerves that provide the main input to dorsal horn interneurones in the same region of the spinal cord. The sources of depolarization of flexor and extensor fibres terminating in the same (sacral) segments were very similar. 4. The amplitudes of field potentials evoked by group II afferents were depressed by the same types of afferent as produced depolarization of group II afferent fibres. There was also a strong correlation between the effectiveness with which afferents of a given nerve induced depolarization of single fibres and depression of field potentials in the same segments. Since group II field potentials were depressed to a greater extent (by up to 90%) than group I field potentials (by no more than 20%) concurrently recorded in the intermediate zone of midlumbar segments, it appears that transmission from group II muscle afferents may be more strongly affected by presynaptic inhibition than that from group I muscle afferents. 5. The results suggest that the interneuronal systems responsible for the presynaptic control of transmission from group II muscle afferents have topographically restricted actions and an organization appropriate to a system of negative feedback control.

• Interneurones mediating presynaptic inhibition of group II muscle afferents in the cat spinal cord.

  Authors: E Jankowska, J S Riddell

  The Journal of physiology. 04/1995; 483 ( Pt 2):461-71.

  1. To investigate whether dorsal horn interneurones with input from group II muscle afferents induce depolarization of sensory fibres, simultaneous recordings were made from single interneurones in1. To investigate whether dorsal horn interneurones with input from group II muscle afferents induce depolarization of sensory fibres, simultaneous recordings were made from single interneurones in the sacral segments and from sacral dorsal root filaments using the spike-triggered averaging technique. 2. The spike potentials of eighteen out of thirty-eight interneurones tested were followed by dorsal root potentials (DRPs). The DRPs occurred at latencies of 2 and 6-8 ms. Interneurones evoking DRPs at latencies of up to 2 ms are considered likely to be last-order interneurones in pathways of presynaptic inhibition, while those inducing DRPs at longer latencies are considered likely to be first-order interneurones. The former were activated by peripheral afferents with somewhat longer latencies than the latter. However, all interneurones were co-activated by group II muscle and cutaneous afferents, indicating that the depolarization of group II muscle afferents, which these afferents induce, may be mediated by the same interneurones. 3. DRPs evoked by electrical stimulation of peripheral nerves were recorded from both sacral and midlumbar dorsal root filaments. The amplitudes of these DRPs were closely related to the potency with which group II afferents of various nerves activate dorsal horn interneurones in the sacral and midlumbar segments and group II afferents contributed to them more effectively than group I afferents. The second stimulus in a train was more effective than the first, while a third stimulus had little additional effect, indicating that the interneurones involved are relatively easily activated. 4. Intraspinal stimuli applied within the dorsal horn, at the sites where the largest field potentials of group II origin were recorded, evoked distinct DRPs. However, the location of the first- and last-order interneurones in pathways of primary afferent depolarization (PAD) could not be differentiated by this approach because the same stimuli induced positive potentials, which masked the onset of DRPs and precluded localization of the sites from which DRPs might be evoked monosynaptically.

• Interneurones in pathways from group II muscle afferents in sacral segments of the feline spinal cord.

  Authors: E Jankowska, J S Riddell

  The Journal of physiology. 04/1994; 475(3):455-68.

  1. Properties of dorsal horn interneurones that process information from group II muscle afferents in the sacral segments of the spinal cord have been investigated in the cat using both intracellular1. Properties of dorsal horn interneurones that process information from group II muscle afferents in the sacral segments of the spinal cord have been investigated in the cat using both intracellular and extracellular recording. 2. The interneurones were excited by group II muscle afferents and cutaneous afferents but not by group I muscle afferents. They were most effectively excited by group II afferents of the posterior biceps, semitendinosus, triceps surae and quadriceps muscle nerves and by cutaneous afferents running in the cutaneous femoris, pudendal and sural nerves. The earliest synaptic actions were evoked monosynaptically and were very tightly locked to the stimuli. 3. EPSPs evoked monosynaptically by group II muscle afferents and cutaneous afferents of the most effective nerves were often cut short by disynaptic IPSPs. As a consequence of this negative feedback the EPSPs gave rise to single or double spike potentials and only a minority of interneurones responded with repetitive discharges. However, the neurones that did respond repetitively did so at a very high frequency of discharges (0.8-1.2 ms intervals between the first 2-3 spikes). 4. Sacral dorsal horn group II interneurones do not appear to act directly upon motoneurones because: (i) these interneurones are located outside the area within which last order interneurones have previously been found and (ii) the latencies of PSPs evoked in motoneurones by stimulation of the posterior biceps and semitendinosus, cutaneous femoris and pudendal nerves (i.e. the main nerves providing input to sacral interneurones) are compatible with a tri- but not with a disynaptic coupling. Spatial facilitation of EPSPs and IPSPs following synchronous stimulation of group II and cutaneous afferents of these nerves shows, however, that sacral interneurones may induce excitation or inhibition of motoneurones via other interneurones. 5. Comparison of the properties of group II interneurones in the sacral segments with those of previously studied group II interneurones in the midlumbar segments leads to the conclusion that these two populations of neurones are specialized for the processing of information from different muscles and skin areas. In addition, equivalents of only one of the two subpopulations of midlumbar interneurones have been found at the level of the pudendal nucleus: neurones with input from group II but not from group I muscle afferents. Neurones integrating information from group I and II muscle afferents and in direct contact with motoneurones thus seem to be scarce in the sacral segments.(ABSTRACT TRUNCATED AT 400 WORDS)

• Ascending tract neurones processing information from group II muscle afferents in sacral segments of the feline spinal cord.

  Authors: J S Riddell, E Jankowska, I Hammar, Z Szabo-Läckberg

  The Journal of physiology. 04/1994; 475(3):469-81.

  1. Ascending tract neurones located in the dorsal horn of sacral segments of the spinal cord have been investigated by extracellular and intracellular recording in the anaesthetized cat. The aim was1. Ascending tract neurones located in the dorsal horn of sacral segments of the spinal cord have been investigated by extracellular and intracellular recording in the anaesthetized cat. The aim was to determine whether information from group II afferents that terminate within the sacral segments is conveyed to supraspinal structures and which types of neurones are involved. 2. A considerable proportion of ascending tract neurones found in the dorsal horn in the same segments as the pudendal (Onuf's) motor nucleus were excited by group II muscle afferents. The great majority (93%) of these neurones had axons ascending in ipsilateral funiculi. Spinocervical tract neurones constituted the largest proportion (82%) of such neurones, while very few spinocerebellar tract and propriospinal neurones and no postsynaptic dorsal column neurones were found among them. 3. In addition to activation by group II muscle afferents all of the neurones were strongly excited by cutaneous afferents. The most potent excitation was evoked by afferents of the posterior biceps-semitendinosus and gastrocnemius muscle nerves and by afferents of the cutaneous femoris, sural and pudendal nerves. The latencies of intracellularly recorded excitatory potentials were indicative of a high incidence of monosynaptic coupling between the afferents and ascending tract neurones. 4. The highly effective monosynaptic excitation of spinocervical tract neurones in the sacral segments by group II afferents is in contrast to the weak disynaptically mediated actions of group II afferents on such neurones in the L6-L7 segments but comparable to the actions of group II afferents on ascending tract neurones in the midlumbar segments. 5. Both the patterns of peripheral input and the latencies of synaptic actions in ascending tract neurones were similar to those in interneurones at the same locations (accompanying report). Similar information is therefore likely to be processed by both categories of neurones. 6. The role of sacral spinocervical tract neurones as a system for transmitting information from group II muscle afferents to supraspinal centres and the potential contribution of this system to the perception of limb position are discussed.

• Morphology of interneurones in pathways from group II muscle afferents in sacral segments of the cat spinal cord.

  Authors: E Jankowska, J S Riddell, Z Szabo-Läckberg, I Hammar

  The Journal of comparative neurology. 12/1993; 337(3):518-28.

  The morphology of 12 sacral interneurones with peripheral input from group II muscle afferents was analyzed after intracellular injection of horseradish peroxidase (HRP). The neurones were located inThe morphology of 12 sacral interneurones with peripheral input from group II muscle afferents was analyzed after intracellular injection of horseradish peroxidase (HRP). The neurones were located in Rexed's laminae III-V overlying the pudendal (Onuf's) motor nucleus. The interneurones had medium sized elongated somata and dendrites projecting radially. All of the interneurones were funicular neurones and fell into two categories depending on whether their axons ran within the dorsal part of the lateral funiculus (DLF; n = 7) or within the ventral funiculus, or the ventral part of the lateral funiculus (VF or VLF; n = 4). The latter were located more rostrally. Within the DLF similar proportions of stem axons and secondary axonal branches descended and ascended. Within the VF and VLF all of the axons ascended. Collaterals of axons running in the DLF arborized primarily within the dorsal horn and the intermediate zone; none were found to approach the motor nuclei. In contrast, collaterals of axons running in the VF/VLF arborized in both the intermediate zone and the ventral horn and passed close to the motor nuclei. We conclude that sacral interneurones with group II input are morphologically nonhomogenous and that only those located most rostrally might have direct actions upon motoneurones. Both the axonal projections and the input (from group II but not from group I muscle afferents and from skin afferents) of sacral interneurones indicate that they are homologous to dorsal horn group II interneurones in the midlumbar segments. They appear, however, to form part of more local neuronal networks than their midlumbar counterparts.

• Primary afferent depolarization of myelinated fibres in the joint and interosseous nerves of the cat.

  Authors: E Jankowska, J S Riddell, D A McCrea

  The Journal of physiology. 08/1993; 466:115-31.

  1. Changes in the excitability of the intraspinal terminals of fibres in the posterior knee joint and interosseous nerves were used as a measure of primary afferent depolarization (PAD) which is1. Changes in the excitability of the intraspinal terminals of fibres in the posterior knee joint and interosseous nerves were used as a measure of primary afferent depolarization (PAD) which is associated with presynaptic inhibition of transmission from afferent fibres. These were estimated from changes in the intensity of electrical stimuli required to activate the fibres in 50% of trials. In order to avoid the inclusion of group I muscle afferents which contaminate the joint and interosseal nerves, the analysis was restricted to fibres conducting at less than 75 m s-1 and/or displaying patterns of PAD which differed from those of group Ia and Ib muscle afferents in lower lumbar segments of anaesthetized cats. PAD was evoked by electrical stimulation of ipsilateral hindlimb nerves. 2. PAD of fibres in the posterior knee joint nerve was induced from group I (Ia and Ib) and group II muscle afferents and cutaneous afferents but not by stimulation of the joint or the interosseous nerves. The most effective stimuli were those applied to the superficial peroneal, sural, quadriceps and posterior biceps and semitendinosus nerves. 3. PAD of fibres in the interosseous nerve was also induced by stimulation of group I (Ia and Ib) and group II muscle afferents and cutaneous afferents and, in addition, by stimulation of joint and interosseous nerves. The most effective stimuli were those applied to the superficial peroneal, quadriceps, flexor digitorum longus and posterior biceps and semitendinosus nerves. 4. Individual fibres of the joint and the interosseous nerves were depolarized by only some of the conditioning stimuli. Even the most effective stimuli did not produce PAD in all of the fibres tested. Individual fibres of the joint and the interosseous nerves were depolarized by diverse combinations of afferents of different functional types and of different peripheral nerves. The differences in the sources of PAD were not associated with the conduction velocities and hence are unlikely to be related to differences in the receptor origin of the tested fibres. The diversity in the sources of PAD of individual fibres is interpreted as providing a high degree of differentiation in the control of transmission from receptors in joints and interosseal membranes.

• A relay for input from group II muscle afferents in sacral segments of the cat spinal cord.

  Authors: E Jankowska, J S Riddell

  The Journal of physiology. 07/1993; 465:561-80.

  1. A neuronal relay for input from group II afferents of hindlimb muscle nerves has been found in the previously little explored sacral segments of the cat spinal cord. 2. Electrical stimulation of1. A neuronal relay for input from group II afferents of hindlimb muscle nerves has been found in the previously little explored sacral segments of the cat spinal cord. 2. Electrical stimulation of group II muscle afferents of a number of nerves evoked negative potentials on the surface (cord dorsum potentials) and population postsynaptic potentials (field potentials) within the sacral segments. The largest potentials were evoked by stimulation of the posterior biceps-semitendinosus and triceps surae nerves which evoke much smaller potentials in other segments. Group II afferents of other nerves, notably those which have their main relay within the middle lumbar segments, were much less effective. 3. The sites at which cord dorsum and field potentials evoked by group II muscle afferents were recorded varied in relation to the external topography of the L7-S2 spinal segments but were consistent in their location relative to the pudendal motor nucleus (Onuf's nucleus). Potentials evoked by group II afferents of the posterior biceps and semitendinosus nerves peaked at a level corresponding to the rostral half of Onuf's nucleus and potentials evoked by afferents of the gastrocnemius nerves peaked just rostral to this nucleus. The largest field potentials (of 0.5-1.0 mV) were recorded within the dorsal horn. Field potentials in the intermediate zone were much smaller (< 0.3 mV) and were seen less frequently. 4. Evidence was obtained that the dorsal horn field potentials are to a great extent evoked monosynaptically by the fast conducting fraction of group II muscle afferents: (i) they were evoked at short latencies (2.4-2.7 ms from the stimulus; 1.3-1.7 ms from group I components of afferent volleys and 0.5-0.7 ms from group II components of these volleys), (ii) the conduction times of impulses in the fastest conducting fraction of group II afferents, between the sacral segments (where these impulses were induced by intraspinal stimuli) and the peripheral nerves, were only about 0.5 ms shorter than the latencies of field potentials recorded at the site of intraspinal stimulation and evoked by stimulation of the same peripheral nerves and, (iii) the field potentials followed repetitive stimuli without temporal facilitation. 5. Negative cord dorsum and field potentials were also evoked by small stretches of the semitendinosus and triceps surae muscles. Although they were smaller than potentials evoked by electrical stimulation of sensory fibres and appeared at longer latencies, their presence is consistent with a contribution of muscle spindle afferents to the actions of group II muscle afferents within the sacral segments.(ABSTRACT TRUNCATED AT 400 WORDS)

• Depolarization of group II muscle afferents by stimuli applied in the locus coeruleus and raphe nuclei of the cat.

  Authors: J S Riddell, E Jankowska, E Eide

  The Journal of physiology. 03/1993; 461:723-41.

  1. Electrical stimuli applied in the locus coeruleus/subcoeruleus (LC/SC) and raphe nuclei produce a profound depression of transmission in reflex pathways from group II muscle afferents. The present1. Electrical stimuli applied in the locus coeruleus/subcoeruleus (LC/SC) and raphe nuclei produce a profound depression of transmission in reflex pathways from group II muscle afferents. The present experiments were performed to determine whether presynaptic inhibitory mechanisms contribute to these effects. 2. Changes in the excitability of afferent terminals to electrical stimuli have been used as an indication of primary afferent depolarization (PAD) produced by conditioning stimuli applied within the LC/SC and raphe nuclei and, for comparison, in the nucleus ruber. Group II afferents originating from ankle flexor muscles and terminating in the midlumbar segments were used for testing. 3. Clear changes in excitability were observed in fourteen of nineteen group II fibres in which the effects of conditioning stimuli applied in the LC/SC were tested and in twelve of seventeen fibres in which the effects of stimuli applied within the raphe nuclei were tested. By comparison, only one of the twelve fibres tested with conditioning stimuli applied to the nucleus ruber was found to be influenced. These effects matched those of the same conditioning stimuli on field potentials evoked by group II afferents at the location at which the terminals of group II fibres were stimulated. 4. Stimuli applied in the LC/SC and in the raphe nuclei both produced a mean decrease in threshold stimulus current of 19%. These effects are comparable to those produced by the most effective volleys in peripheral afferent which, in the same fibres, produced a mean decrease in threshold stimulus current of 24%. 5. In all cases (twelve) in which the effects of stimuli applied in the LC/SC and raphe nuclei were tested on the same group II fibre, either both or neither were found to be effective. This strengthens previous indications that some populations of neurones might be activated by stimuli applied in each of these regions of the brain. 6. In contrast to group II afferents, group Ia afferents investigated in the same experiments were only exceptionally affected. Of seven fibres tested with stimuli applied in the LC/SC, six with stimuli applied in the raphe nuclei and seven with stimuli applied in the nucleus ruber, only one fibre showed any clear change in threshold and this was a single fibre which was similarly affected by stimuli in all three sites. 7. It is concluded that presynaptic inhibitory mechanisms contribute to the depression of transmission in spinal reflex pathways from group II muscle afferents produced by stimulation in the LC/SC and raphe nuclei.

• Gating of transmission to motoneurones by stimuli applied in the locus coeruleus and raphe nuclei of the cat.

  Authors: E Jankowska, J S Riddell, B Skoog, B R Noga

  The Journal of physiology. 02/1993; 461:705-22.

  1. Neuronal systems activated by stimulation in the region of the locus coeruleus/subcoeruleus (LC/SC) and raphe nuclei have previously been shown to depress transmission from group II muscle1. Neuronal systems activated by stimulation in the region of the locus coeruleus/subcoeruleus (LC/SC) and raphe nuclei have previously been shown to depress transmission from group II muscle afferents in regions of the midlumbar spinal segments in which premotor interneurones are located. The aim of the present investigation was to determine the extent to which such depression is paralleled by depression of the reflex actions of group II afferents on motoneurones. 2. The effects of short trains of conditioning electrical stimuli applied within the LC/SC and raphe nuclei were examined on postsynaptic potentials (PSPs) evoked by group I and group II muscle afferents in hindlimb motoneurones. The effects were examined over a wide range of conditioning-test intervals but particular emphasis was placed on the effects produced at long intervals (> 100 ms) since such effects are more likely to be mediated by the descending noradrenergic and serotonergic neurones of the LC/SC and raphe nuclei which are of slow conduction velocity. In addition, conditioning stimuli alone evoked PSPs in motoneurones (with latencies of 7-15 ms and a duration of 50-80 ms) and effects evoked at short conditioning-test intervals might therefore have been secondary to changes in motoneurone membrane properties. 3. At conditioning-test intervals between 100 and 350 ms synaptic actions of group II origin were strongly and consistently depressed. Both EPSPs and IPSPs were affected, two-thirds of those tested being reduced in amplitude by 50% or more. A similar depression was exerted on PSPs evoked from the quadriceps and deep peroneal nerves mediated predominantly by interneurones located in the midlumbar segments and on PSPs evoked from the hamstring and triceps surae nerves mediated by interneurones located in more caudal segments. It is thus concluded that neuronal systems activated by stimuli applied in the LC/SC and raphe nuclei are capable of gating transmission in all those interneuronal pathways which mediate the reflex actions of group II afferents on motoneurones in anaesthetized animals.

• A group II-activated ascending tract of lumbosacral origin in the cat spinal cord.

  Authors: P J Harrison, J S Riddell

  The Journal of physiology. 07/1990; 425:379-90.

  1. Electrophysiological investigations have revealed a population of ascending tract neurones originating in the lumbosacral enlargement, with input from group II muscle afferents of the cat1. Electrophysiological investigations have revealed a population of ascending tract neurones originating in the lumbosacral enlargement, with input from group II muscle afferents of the cat hindlimb. 2. Single-unit microelectrode recordings were made in the lateral funiculus at L6, from the axons of thirty-four ascending tract neurones. All of the axons were antidromically activated by stimulation of the ipsilateral lateral funiculus at Th13 and, whenever tested (eight units), at C1. 3. Conduction velocities of the axons, between the L6 and Th13 segment, ranged from 33 to 92 m s-1 (mean 61 m s-1). 4. All of the ascending tract neurones were discharged following electrical stimulation of muscle nerves at group II strength, but not by weaker stimuli in the group I range. Most of the investigated neurones were excited by group II afferents of more than one muscle nerve. In addition, a proportion of the units tested could also be discharged by cutaneous and by joint afferents. 5. Responses to natural stimuli were investigated in eighteen ascending tract neurones discharged by electrical stimulation of group II afferents in the gastrocnemius-soleus (GS) and plantaris (P1) nerves which were dissected free in continuity with their muscles. Seven units were spontaneously active. Eight units responded to isometric contraction of the GS/P1 muscles with a discharge occurring mainly on the falling phase of muscle tension. Nine units increased their discharge frequency in response to stretching of the muscles and five units responded to mechanically probing the muscles with a blunt instrument. 6. The final termination sites of this group of ascending tract neurones has yet to be determined. Initial attempts (three units) to antidromically activate the neurones from the cerebellum have been unsuccessful. Other likely areas of termination in the brain stem are considered.