Ipsilateral Dorsolateral Funiculus Research Articles

Paradoxical Sleep Deprivation Aggravates and Prolongs Incision-Induced Pain Hypersensitivity via BDNF Signaling-Mediated Descending Facilitation in Rats.

The mechanisms underlying the pronociceptive effect of paradoxical sleep deprivation (PSD) are not fully established. The modulation of BDNF signaling-mediated descending facilitation from the rostral ventromedial medulla (RVM) of brain stem has been demonstrated in persistent pain models of inflammatory pain, but not in incisional pain model. Recent study has shown that PSD increases the expression of brain-derived neurotrophic factor (BDNF) in the brainstem structure. Therefore, in the current study, we asked whether the BDNF signaling-mediated descending facilitation was involved in the PSD-induced pronociceptive effect on incisional pain and delay the recovery period of postoperative pain in rats. Our results found that a preoperative 24h PSD significantly aggravated the pain hypersensitivity after incision and prolonged the duration of postoperative pain. The lesions of ipsilateral dorsolateral funiculus partly reversed the PSD-induced pronociceptive effect on incisional pain. Interestingly, the 24h PSD, but not incision significantly enhanced the levels of BDNF protein expression in the RVM areas of rats. Furthermore, at 1day or 4days after incision, intra-RVM microinjection of a BDNF antibody partly reversed the PSD-induced pronociceptive effects in incisional rats, while it did not change the cumulative pain scores and paw withdrawal thresholds in rats receiving only plantar incision. These findings suggest that the preoperative PSD may aggravate and prolong the incision-induced pain hypersensitivity via BDNF signaling-mediated descending facilitation.

Differential input to dorsal horn dorsal spinocerebellar tract neurons in mid- and low-lumbar segments from upper cervical spinal cord in the cat

Previous studies showed that ipsilaterally projecting dorsal horn dorsal spinocerebellar tract (dh-DSCT) neurons located outside Clarke's column in mid- and caudal-lumbar segments of the spinal cord receive different afferent inputs. Here, we examined, using extracellular recordings in anaesthetized cats, whether there are also input differences to these populations of dh-DSCT neurons from: (a) the spinocervical tract (SCT), estimated by stimulation of the ipsilateral dorsolateral funiculus at cervical cord C3 and rostral C1, below and above the termination of SCT axons in the lateral cervical nucleus (LCN), and (b) descending/ascending fibres activated by electrical stimulation at rostral C1. Seventy percent (21/30) of the lower-lumbar (L6–L7) dh-DSCT neurons received significantly greater excitation from C3 than rostral C1, whereas only 17% (5/30) of the mid-lumbar (L5) dh-DSCT neurons had greater responses from C3 than rostral C1. Inhibition of background activity was seen in 30% of the lower-lumbar neurons, but only in 3% of mid-lumbar neurons. These findings suggest that lower-lumbar dh-DSCT neurons are much more likely, than mid-lumbar ones, to be influenced by the SCT and by systems descending from the brain, LCN and/or ascending systems. The experiments provide further evidence for differences in input to the subpopulations of dh-DSCT neurons.

Quantitative inter-segmental and inter-laminar comparison of corticospinal projections from the forelimb area of the primary motor cortex of macaque monkeys

Corticospinal projections from the forelimb area of the primary motor cortex to the C2–Th2 spinal cord segments were quantitatively analyzed using the high resolution anterograde tracer, biotinylated dextran amine (BDA), in rhesus monkeys ( n=5). The majority of descending axons were located in the contralateral dorsolateral funiculus (DLF) (85–98%), but a minor portion was observed in the ipsilateral DLF (1–12%) and ventromedial funiculus (VMF) (1–7%). In the gray matter, axon collaterals and terminal buttons were found mainly in the contralateral laminae VI–VII and IX and ipsilateral lamina VIII. The majority of projections to the contralateral gray matter originated from the contralateral DLF, but a minority originated from the ipsilateral DLF. Axons from the ipsilateral DLF were not found to project collaterals on the ipsilateral side, but directly entered the contralateral side after crossing the midline. On the other hand, projections to the ipsilateral lamina VIII were from the ipsilateral VMF, and commissural axons were from the contralateral DLF. Terminal buttons in the motoneuron pool in the contralateral lamina IX were found mainly at the C7–Th1 spinal cord segments, whereas the projections to the contralateral laminae VI–VII, ipsilateral lamina VIII, and commissural axons were also found in more rostral segments, abundantly at the C4–C8 segments, 1–3 segments rostral to the motoneuronal projections. These results suggest that cortical control of contralateral forelimb motoneurons accompanies regulation of interneuronal systems in the contralateral laminae VI–VII and the ipsilateral lamina VIII located a few segments rostral to the motoneurons.

Electrophysiological actions of the rubrospinal tract in the anaesthetised rat

The rubrospinal tract (RST) of the rat is widely used in studies of regeneration and plasticity, but the electrophysiology of its spinal actions has not been described. In anaesthetised rats with neuromuscular blockade, a tungsten microelectrode was located in the region of the red nucleus (RN) by combining stereotaxis with recording of antidromic potentials evoked from the contralateral spinal cord. Single stimuli through this electrode typically elicited two descending volleys in the contralateral dorsolateral funiculus (DLF) separated by about 1 ms, and one volley recorded from the ipsilateral DLF. Latencies of the ipsilateral and the early contralateral volley were similar. The activation of these volleys depended on the location of the stimulation site in or near the RN. Evidence is adduced to show that: (a) the late contralateral volley is carried by fibres of RST neurones, synaptically activated; (b) the early contralateral volley is mostly carried by RST fibres stimulated directly; (c) the ipsilateral volley is sometimes carried by RST fibres from the RN on the side contralateral to the stimulus; (d) otherwise, either early volley may derive from fibres in other tracts. Synaptic potentials related to the volleys were recorded within the cervical enlargement and their distribution plotted on cross-sections of the spinal cord. These measurements suggest that the great majority of RST terminations are on interneurones in the intermediate region contralateral to the RN. Direct synaptic actions on motoneurones are likely to be weak. Stimulation parameters appropriate for specific activation of the RST in future studies are suggested.

Stochastic Resonance within the Somatosensory System: Effects of Noise on Evoked Field Potentials Elicited by Tactile Stimuli

Stochastic resonance (SR) is commonly understood to be the enhancement, by noise, of the response of a system to a weak input signal. The aim of this study was to demonstrate the occurrence of SR in spinal and cortical evoked field potentials (EFPs) elicited by periodic tactile stimuli in the anesthetized cat. The electrodes were positioned in spinal and cortical somatosensory regions in which the largest negative EFPs were detected. The periodic tactile stimuli consisted of local skin displacements on the central pad of the hindpaw. Two series of experiments were performed. First, periodic tactile stimuli and the noisy tactile stimuli were applied with the same indenter. Second, noisy tactile stimuli were applied with an additional indenter placed on the glabrous skin of the third hindpaw digit. This last protocol ensured that the signal and noise were mixed not in the skin but in the somatosensory regions of the CNS. All cats showed distinct SR behavior at the spinal and cortical stages of the sensory encoding. Such SR was abolished in the cortical but not in the spinal recording after sectioning of the dorsal columns and the ipsilateral dorsolateral funiculus. This suggests that the spinal neurons may also contribute to the SR observed at the cortical level. To the best of our knowledge, this is the first documented evidence that such a remarkable phenomenon embodies electrical processes of the spinocortical somatosensory system itself.

Cortical neuronal ensembles driven by dorsal horn spinal neurones with spontaneous activity in the cat

Simultaneous recordings of cortical activity, recorded as the cortical local field potential (CLFP) in the contralateral posterior sigmoid gyrus, and the spinal activity, recorded as the cord dorsum potential (CDP) of the L6 lumbar segment, were made in the anaesthetized cat. The electrodes were positioned in somatosensory regions where the largest spontaneous negative CLFPs and CDPs were recorded. We found that spontaneous negative CLFPs were preceded by spontaneous negative CDPs with a mean latency of 14.4±3.5 ms. Amplitude of these spontaneous negative CLFPs was abolished after section of the dorsal columns and ipsilateral dorsolateral funiculus. It is concluded that the neurones of the primary somatosensory cortex can be driven by dorsal horn spinal neurones producing the spontaneous negative CDPs. This suggests very strongly that spontaneous neuronal activity in somatosensory regions of the brain is generated not only by ongoing activity of neurones located at supraspinal sites, but also by ongoing activity of spinal neurones.

Spino-bulbo-spinal pathway mediating vagal modulation of nociceptive-neuroendocrine control of inflammation in the rat.

Stimulation of nociceptors by intradermal capsaicin produces depression of bradykinin (BK)-induced synovial plasma extravasation (PE) that is markedly enhanced by subdiaphragmatic vagotomy. This depression is mediated by the adrenal medullae, a propriospinal pathway between the afferent nociceptive input and preganglionic neurones projecting to the adrenal medullae, and a spino-bulbo-spinal pathway. Here we investigated the role of spinal ascending and descending pathways in the interaction between noxious and vagal afferent inputs, leading to inhibition of BK-induced PE mediated by the adrenal medullae. Nociceptors in the paw were activated by capsaicin and depression of BK-induced PE was measured in rats with intact or cut subdiaphragmatic vagus nerves. After cutting the dorsolateral funiculus (DLF) contralateral to the stimulated hindpaw (segmental level C5/C6 and T8/T9), depression of BK-induced PE was weak or absent both in rats with intact vagus nerves and in vagotomised rats, suggesting that an ascending excitatory pathway was interrupted. After cutting the DLF ipsilateral to the stimulated hindpaw, depression of BK-induced PE was already markedly enhanced, even in the absence of vagotomy. Ipsilateral DLF lesion (L2/L3) below the level of the spinal output to the adrenal medullae produced the same effect, suggesting interruption of a descending inhibitory pathway that relays the effect of vagal activity to the level of the capsaicin-induced nociceptive input. Contralateral and ipsilateral hemisection of the spinal cord (C5/C6) produced the same changes as the corresponding DLF lesions. Ipsi- or contralateral lesion of the dorsal funiculus at the spinal level T8/T9 had no effect on depression of BK-induced PE generated by cutaneous noxious stimulation of the forepaw. We suggest that noxious stimulation activates an ascending pathway of the spino-bulbo-spinal excitatory circuit which projects through the DLF contralateral to the nociceptive input, and that the inhibitory pathway which is activated by vagal afferent activity projects through the DLF ipsilateral to the nociceptive input.

Lesions of the dorsolateral funiculus block supraspinal opioid delta receptor mediated antinociception in the rat

Previous experiments have demonstrated that [D-Ala 2,Glu 4]deltorphin (DELT) produces δ-receptor mediated antinociceptive effects when microinjected into the rat lateral ventricle and ventral medial medullary reticular formation (MRF), but not in the periaqueductal grey region (PAG). The present experiments were undertaken to further characterize the role of δ opioid agonists microinjected into the MRF and to explore the possibility of a descending pain modulatory system which might be linked to supraspinal δ opioid receptors. Rats received formalin into the dorsum of the right hindpaw and flinching responses were recorded. DELT given intracerebroventricularly (i.c.v.), intrathecally (i.th.) or into the MRF before formalin produced a dose-dependent and δ opioid receptor-mediated attenuation of both the first and second phases of the formalin-induced foot flinch response. DELT given i.c.v., i.th., or into the MRF also blocked formalin-induced increase in Fos-like immunoreactivity (FLI) in the dorsal horn of lumbar spinal cord ipsilateral to the formalin injection. Unilateral lesioning of the ipsilateral dorsolateral funiculus (DLF) did not alter nociceptive responses to formalin alone, but blocked the antinociceptive effect of DELT administered into the MRF; DELT was fully active in sham-DLF lesioned rats. Additionally, rats with DLF lesions did not show decreases in formalin-induced FLI in the ipsilateral lumbar spinal cord after injection of DELT into the MRF. These data suggest that δ opioid receptors in the MRF may be involved in activation of a descending inhibitory pain pathway projecting through the DLF to modulate tonic nociceptive input at the spinal level.

Interrelations of opioids with monoamines in descending inhibition of nociceptive transmission at the spinal level: an immunocytochemical study

This study was designed to reexamine a previous proposal of whether the opioid-like substances (OLS) being acting mainly as an intrinsic spinal mediator in the descending inhibition of nociception of the bulbospinally projecting NE-ergic, and/or 5-HT-ergic terminals in the dorsal horn by using an immunocytochemical method. The effects of intrathecal (i.t.) phentolamine (Ph), cyproheptadine (Cyp), and naloxone (Nal), administered separately or coadministered by two of them, on the expression of Fos-like-immunoreactive (FLI) neurons were observed on both sides of the lumbar dorsal horn of rats, in which equal volumes of formalin were injected into two hindpaws and the ipsilateral dorsolateral funiculus (DLF) was transected at the thoracic level antecedently. The results showed: (1) when rats were pretreated with i.t. saline, the number of nociceptive FLI neurons was significantly lowered 44% ( p<0.01) on the side of the lumbar dorsal horn with intact DLF compared to the opposite side with sectioned DLF; (2) when rats were separately pretreated with i.t. Ph, Cyp and Nal, the reduction of FLI neurons on the DLF-intact side were decreased by 27% ( p<0.01), 21% ( p<0.01), and 25% ( p<0.01), respectively; (3) when rats were pretreated with combined i.t. Ph+Cyp, the reduction on the intact side was eliminated almost completely (4%); (4) when rats were pretreated with combined i.t. Ph+Nal, the reduction on the intact side was 21% ( p<0.01); and (5) when rats were pretreated with i.t. Cyp+Nal, the reduction on the intact side was 9.1%. These results suggest that: (1) nearly all the suppressive action exerted by the DLF-descending fibers are produced by the release of either NE or 5-HT as neurotransmitters at the spinal level; (2) most of the opioid-like substances act as an intrinsic spinal mediator mainly for the descending NE-ergic, but in a lesser extent for the 5-HT-ergic terminals in the dorsal horn circuitry; and (3) some OLS-ergic interneurons may only be activated by local nociceptive input.

Pharmacological evidence for a periaqueductal gray–nucleus raphe magnus connection mediating the antinociception induced by microinjecting carbachol into the dorsal periaqueductal gray of rats

A previous study demonstrated that microinjection of carbachol (CCh) into the dorsal periaqueductal gray matter (dPAG) of rats increases the latency for the tail flick reflex. Several other studies have implicated the raphe magnus (NRM) and the reticularis paragigantocellularis (NRPG) nuclei as relay stations through which descending pathways from the PAG project to the spinal cord via the dorsolateral funiculus (DLF). In the present study, the effects of microinjecting CCh into the dPAG on the tail flick test were examined in rats in which the ipsilateral DLF was previously lesioned, or saline or lidocaine (2%) was microinjected into the NRM or ipsilateral NRPG. The DLF lesion did not change the baseline threshold of the animals in the test, but abolished the CCh-induced increase in the tail flick latency from the dPAG. The neural block of the NRM or NRPG with lidocaine also did not change significantly the latency for the tail flick reflex. The increase in the tail flick latency produced by CCh from the dPAG was not changed by the neural block of the NRPG, but was significantly reduced by the neural block of the NRM. These results are interpreted as indicative that the central antinociceptive mechanisms activated by CCh from the dPAG depend on a descending pathway that projects to the spinal cord via DLF utilizing at least the NRM, but not the NRPG, as an intermediary relay station.

Indications for coupling between feline spinocervical tract neurones and midlumbar interneurones.

The possibility of collateral segmental actions of spinocervical tract (SCT) neurones upon interneurones with input from cutaneous and group II muscle afferents was investigated in deeply anaesthetized cats. To this end, intracellular and/or extracellular recordings were made from 35 dorsal horn and 15 intermediate zone interneurones in midlumbar segments of the spinal cord and effects of stimulation of the ipsilateral dorso-lateral funiculus (DLF) at C3 and C1 levels, i.e. below and above the lateral cervical nucleus where axons of SCT cells terminate, were compared. The stimuli applied at the C3 segment were within the range of stimuli (50-100 microA) required for antidromic activation of SCT neurones in the same experiment. Those applied at the C segment (200-500 microA) were at least 3 times stronger than C3 stimuli. Under the same experimental conditions, long ascending and descending tract neurones (dorsal spino-cerebellar and rubro-spinal tract neurones) with axons in the DLF were activated at similar thresholds from the C and C3 segments. Intracellular recordings were made from 29 interneurones of which 19 (65%) were dorsal horn and 10 (35%) were intermediate zone interneurones. Excitatory postsynaptic potentials (EPSPs) evoked by single stimuli applied at the C3 segment, but not the C segment, were found in 14 (48%) of those interneurones; their latencies (3.0-5.7 ms) and frequency following with only minimal temporal facilitation were as required for potentials being evoked monosynaptically by the fastest conducting SCT neurones. Extracellular recordings were made from 30 interneurones (24 dorsal horn and 6 intermediate zone interneurones), and in these neurones spike potentials induced from the C3, but not from the C segment, were evoked only by short trains of stimuli. However, their latencies from the first effective stimulus (4.3-5.4 ms) were compatible with mono- or oligosynaptically mediated collateral actions of SCT neurones. They were found in 10 (33%) of the 30 investigated interneurones. Similar effects of C3 stimuli were found in similar proportions of dorsal horn interneurones and intermediate zone interneurones. Indications were also found for synaptic actions evoked by C3 stimuli that could not be attributed to direct collateral actions of SCT neurones. In some intracellularly recorded dorsal horn interneurones, short-latency EPSPs were evoked from the C3 segment by the 2nd or 3rd stimulus in the train, but not by single stimuli. In other dorsal horn and intermediate zone interneurones, inhibitory postsynaptic potentials (IPSPs) were evoked from the C3 segment at minimal latencies (2.7-3.2 ms), which might be too short to allow their mediation via SCT neurones. We conclude that SCT neurones might be used to forward information from muscle group II and cutaneous afferents not only to neurones in the lateral cervical nucleus and via them to thalamus and cerebral cortex but also to interneurones in spinal reflex pathways. Thereby reflex actions evoked from group II and cutaneous afferents might be co-ordinated with responses mediated by supraspinal neurones. We conclude also that dorsal horn and intermediate zone mid-lumbar interneurones might contribute to the previously reported di-and poly-synaptic excitation or inhibition of postsynaptic dorsal column (PSDC), spinothalamic tract (STT) and spinomesencephalic tract (SMT) neurones by collateral actions of SCT cells. Thereby these interneurones might contribute to the co-ordination of responses mediated by various populations of supraspinal neurones.

Supraspinal inhibition of nociceptive dorsal horn neurones in the anaesthetized rat: tonic or dynamic?

1. Tonic inhibition of sensory spinal neurones is well known to descend from the rostroventral medulla. It is not clear if this inhibition is dynamically activated by peripheral noxious stimuli. 2. Transection of the ipsilateral dorsolateral funiculus (DLF) removed a descending inhibition of multireceptive spinal neurones and disproportionally prolonged the after-discharge component of their response to a noxious cutaneous stimulus. 3. Microinjection of GABA or tetracaine into the medullary nucleus gigantocellularis pars alpha (GiA) similarly prolonged the after-discharge in response to noxious stimuli. 4. Recordings of GiA cells, initially using minimal surgery, revealed that many had low levels of spontaneous activity and responded vigorously to noxious stimuli applied to any part of the body surface. One hour after the surgery necessary to expose the spinal cord, GiA cells had a high firing rate but responded weakly to noxious stimuli. 5. The response of GiA cells to noxious stimuli was abolished by transection of only the DLF contralateral to the stimulus. 6. It is concluded that the inhibition of multireceptive dorsal horn neurones from GiA is dynamically activated by noxious cutaneous stimuli via a projection in the contralateral DLF. Surgical exposure of the spinal cord tonically activates this inhibition and masks the dynamic component.

Stretch Hyperreflexia of Triceps Surae Muscles in the Conscious Cat after Dorsolateral Spinal Lesions

Resistive force and electromyograms from triceps surae muscles were measured during dorsiflexion of both ankles of awake cats before and after interruption of one dorsolateral funiculus (DLF). DLF lesions produced ipsilateral increases in dynamic and static reflex force that persisted over 66 weeks. The increase in dynamic reflex force was velocity sensitive, as demonstrated by a greater effect for 60 degrees /sec than for 10 degrees /sec dorsiflexion. Also, the lesions increased dynamic force to a greater extent than static force (increased dynamic index). Background force (recorded immediately before each reflex response) was elevated ipsilaterally. However, increases in reflex force were observed when preoperative and postoperative background forces were matched within 10% and were associated with equivalent resting levels of electromyographic (EMG) activity. Resistive reflex force was significantly correlated with EMG responses to dorsiflexion and was not determined by nonreflexive mechanical stiffness of the muscles. Contralateral background and reflex force and associated EMG activity were decreased slightly, comparing preoperative and postoperative records. Clinical testing revealed ipsilateral postoperative increases in extensor tone, increased resistance to hindlimb flexion, hypermetria during positive support responses, and appearance of the Babinski reflex. However, the most reliable tests of DLF lesion effects were the quantitative measures of dynamic and static reflex amplitude. The enhancement of stretch reflexes is suggestive of spasticity. However, hyperactive stretch reflexes, hypertonicity, and the Babinski reflex were observed soon after interruption of the ipsilateral DLF, in contrast to a gradual development of positive signs that is characteristic of a more broadly defined spastic syndrome from large spinal lesions. Also, other signs that often are included in the spastic syndrome, including clonus, increased flexor reflex activity, and flexor spasms, did not result from DLF lesions. Thus, unilateral DLF lesions provide a model of spasticity but produce only several components of a more inclusive spastic syndrome.

Anterior pretectal nucleus facilitation of superficial dorsal horn neurones and modulation of deafferentation pain in the rat.

1. Functional relationships between the anterior pretectal nucleus (APTN) and nociceptive dorsal horn neurones were investigated electrophysiologically in the anaesthetized rat. The effects of APTN lesions were assessed behaviourally in a model of deafferentation pain. 2. Cells in the dorsal and rostral parts of the APTN were excited orthodromically by electrical stimulation of the ipsilateral dorsolateral funiculus or the contralateral dorsal columns, and by noxious and innocuous cutaneous stimuli. 3. Electrical stimulation of the APTN excited nociceptive lamina I spinal neurones. These cells all projected rostrally in the contralateral dorsolateral funiculus. Identical APTN stimulation also inhibited multireceptive spinal neurones which lay deep in the dorsal horn. These particular cells were shown to project to the brain in the ventrolateral funiculus. 4. It is proposed that noxious stimuli excite spinal lamina I projection neurones which send excitatory axons to the brain, including the APTN. The APTN inhibits deep multireceptive neurones, to reduce the perception of noxious stimuli. The discharge of spinal lamina I neurones, however, will be sustained by the noxious stimulus and by facilitation from the APTN. A sustained descending inhibition of this nature would reduce responses to prolonged injury. 5. The involvement of the APTN in responses to a chronic pain state was examined by comparing the behaviour of animals with bilateral lesions of the APTN with normal controls. Lesions of the APTN strongly enhanced the autotomy behaviour triggered by sectioning of the dorsal roots. 6. These observations support the suggestion that the APTN reduces the debilitating effects of prolonged injury.

Dorsal horn projection targets of ON and OFF cells in the rostral ventromedial medulla.

1. The rostral ventromedial medulla (RVM) participates in the modulation of nociceptive transmission by spinal cord neurons. Previous anatomic studies have demonstrated that RVM neurons project to laminae I, II, and V of the dorsal horn; laminae VII and VIII of the intermediate and ventral horns; the intermediolateral column; and lamina X. The RVM contains at least three physiologically defined classes of neurons, two of which, the ON and the OFF cells, have been implicated in nociceptive modulation. Because these cells classes are intermingled in the RVM, it has not been possible to determine the spinal laminar projection targets of ON and OFF cells by anatomic methods. Therefore in the current study we employed antidromic microstimulation methods to determine the laminar projections of two of the three classes of RVM neurons, the ON and the OFF cells. 2. In lightly anesthetized (with methohexital sodium) rats, single-unit extracellular recordings were made from 48 RVM neurons that were physiologically characterized as ON (30) or OFF (18) cells. The recording locations of 45 of these neurons were recovered. Thirty-seven were found in the nucleus raphe magnus and eight were located near its dorsal and lateral borders. 3. Thirty-two physiologically identified RVM neurons (18 ON and 14 OFF cells) were antidromically activated from the cervical spinal cord using a monopolar stimulating electrode. The stimulating electrode was moved systematically in the white matter until antidromic activation could be produced with currents of < or = 20 microA (6.1 +/- 0.7 microA, mean +/- SE). The points from which minimum currents were required to antidromically activate the neurons were located mainly in the ipsilateral dorsolateral funiculus (DLF) (27 of 32). In a few cases, lowest antidromic threshold currents were found near the border between the DLF and ventrolateral funiculus (VLF) or, rarely, in the VLF itself. In these cases, the cell recordings were found to be near the dorsal boundary of the RVM. 4. While one electrode was used to stimulate the parent axon in the lateral funiculus, a second was used to explore the gray matter for the presence of collateral branches. The identification of a branch was initially determined by an increase in antidromic latency. At the same rostrocaudal plane of the spinal cord, stimulation of the DLF induced an antidromic spike that invaded the neuron earlier than the antidromic spike elicited by stimulation in the gray matter. Collateral branches were confirmed by establishing that the location of the minimum threshold point for antidromic activation of the neurons from the second electrode was in the gray matter, that the minimum current required to antidromically activate the neuron from that point was too low to activate the parent axon in the DLF, and that a collision occurred between the spikes induced by the two stimulating electrodes. 5. In 17 cases, physiologically identified RVM neurons (10 ON and 7 OFF cells) were antidromically activated from the gray matter of the cervical spinal cord using a current of 8.4 +/- 2.1 (SE) microA. Minimum threshold points for antidromic activation were found in laminae I-II (3 ON and 4 OFF cells), lamina V (5 ON and 6 OFF cells), and regions ventral to the lateral reticulated area (3 ON and 2 OFF cells) of the gray matter. As indicated by these numbers, some neurons were antidromically activated from more than one gray matter region. In general, all OFF cells and 9 of 10 ON cells were antidromically activated from low threshold points in either laminae I-II or lamina V. 6. In six cases, neurons were activated from separate points located in two or three different laminae of the gray matter. Three OFF cells were activated from laminae I-II and V, one OFF cell and one ON cell were activated from lamina V and from more ventral points, and one ON cell was activated from laminae I-II and from points ventral to lamina V.

Effects of upper cervical spinal cord stimulation on neurons in the lumbosacral enlargement of the cat: spinothalamic tract neurons

Extracellular microelectrode recordings were made from deep spinothalamic tract neurons in the lumbosacral spinal cord of cats anaesthetized with chloralose and paralyzed with gallamine triethiodide. The effects of upper cervical spinal cord stimulation were tested on 43 spinothalamic tract neurons, by stimulation of the ipsilateral dorsolateral funiculus at C3 and rostral C1 using five or six shocks at 333 Hz. The strength of cervical stimulation was adjusted so that the C3 shock was above threshold for antidromic activation of spinocervical tract neurons but the same strength of shock applied at C1 was below threshold for the same neurons. Four of the 43 spinothalamic cells (9%) were not influenced by upper cervical stimulation. The remaining 39 spinothalamic tract cells (91%) were all excited from the upper cervical cord. Twenty-seven of these (63%) were excited more strongly from C3 than from C1, 4 (9%) were excited more strongly from C1 than from C3, and the remaining eight cells (19%) showed no significant differences between their responses to stimulation at C1 and C3. There were no obvious differences between those spinothalamic tract neurons showing differential effects from C1 and C3 and those showing no such effects. The neuronal systems possibly responsible for the differential effects from C3 and C1 on spinothalamic tract neurons are discussed. We conclude that the most likely candidate system for the greater excitation from C3 compared with C1 is the subset of spinocervical tract neurons with axon collaterals in the lumbosacral enlargement and that the spinothalamic tract is a further ascending path, in addition to the postsynaptic dorsal column path, that receives excitatory input from spinocervical axon collaterals. The greater excitation from C1 compared with C3 is interpreted as due to excitation from C1 and a mixture of excitation and inhibition from C3. The responsible neuronal systems seem likely to be either the spinocervical neurons with axon collaterals operating on the spinothalamic tract via inhibitory interneurons, or cells in the lateral cervical nucleus with axons descending to the lumbosacral cord.

Raphe magnus and reticulospinal actions on primary afferent depolarization of group I muscle afferents in the cat.

1. In the anaesthetized cat, electrical stimulation of the bulbar reticular formation produced a short latency (2.1 +/- 0.3 ms) positive potential in the cord dorsum. In contrast, stimulation of the nucleus raphe magnus with strengths below 50 microA evoked a slow negative potential with a mean latency of 5.5 +/- 0.6 ms that persisted after sectioning the contralateral pyramid and was abolished by sectioning the ipsilateral dorsolateral funiculus. 2. The field potentials evoked by stimulation of the bulbar reticular formation and of the nucleus raphe magnus had a different intraspinal distribution, suggesting activation of different sets of segmental interneurones. 3. Stimulation of these two supraspinal nuclei produced primary afferent depolarization (PAD) in single Ib fibres and inhibited the PAD elicited by group I volleys in single Ia fibres. The inhibition of the PAD of Ia fibres produced by reticulospinal and raphespinal inputs appears to be exerted on different interneurones along the PAD pathway. 4. It is concluded that, although reticulospinal and raphespinal pathways have similar inhibitory effects on PAD of Ia fibres, and similar excitatory effects on the PAD of Ib fibres, their actions are conveyed by partly independent pathways. This would allow their separate involvement in the control of posture and movement.

Distribution of spinal cord projections from the medullary subnucleus reticularis dorsalis and the adjacent cuneate nucleus: A phaseolus vulgaris‐ leucoagglutinin study in the rat

The distribution and organization of descending spinal projections from the dorsal part of the caudal medulla were studied in the rat following injections of Phaseolus vulgaris-leucoagglutinin into small areas of the subnucleus reticularis dorsalis (SRD) and the adjacent cuneate nucleus (Cu). The caudal aspect of the Cu projected only to the dorsal horn of the ipsilateral cervical cord via the dorsal funiculus. These projections were mainly to laminae I, IV, and V. More ventrally located reticular structures projected to the full length of the cord. Fibers originating from the SRD travelled through the ipsilateral dorsolateral funiculus and terminated within the deep dorsal horn and upper layers of the ventral horn, mainly in laminae V-VII. Fibers originating from subnucleus reticularis ventralis (SRV) travelled ipsilaterally through the lateral and ventrolateral funiculi and bilaterally through the ventromedial funiculus. These fibers terminated within the ventral horn. The density of labeling within the gray matter varied at different levels of the cord was as follows: cervical > sacral > thoracic > lumbar. The reciprocal connections between the caudal medulla and the spinal cord suggest that the former is an important link in feedback loops that regulate spinal outflow.

Lumbosacral spinal neurons in the cat that are candidates for being activated by collaterals from the spinocervical tract

Lumbosacral spinal neurons activated via the spinocervical tract were stained by intracellular injection of horseradish peroxidase in cats anaesthetized with chloralose and paralysed with gallamine triethiodide. The neurons were activated orthodromically by single shock stimulation of the ipsilateral dorsolateral funiculus at the second to third cervical segment, but not from the rostral part of the first cervical segment. Twenty nine cells were recovered from the histological material and subsequently reconstructed from transverse sections. Sixteen cells (55%) had axons that projected ipsilaterally to the lateral funiculus and their somata were located in two regions of the spinal cord, one group in the dorsal horn (laminae IV-V) and the other in the intermediate gray matter (laminae VI-VII). The axons of 10 of these cells gave off collaterals, and in seven of them the collaterals ramified in the grey matter deep to the cell body. The axons of five cells (17%) projected medially towards the central canal, four crossing the mid line in the ventral white commissure and ascending in the contralateral ventral funiculus. Only one of these cells had an axon collateral that crossed into the contralateral dorsal horn. Of the remaining eight cells, three had no obvious long axons but had many local axon collaterals, the axons of three cells were not stained, one had an axon projecting towards the ipsilateral ventral funiculus and one was a motoneuron and its axon projected into a ventral root. A feature of the dendritic trees of many cells was their wide spread in the mediolateral and/or the dorsoventral directions, although no dendrites reached dorsally into lamina II. Twenty-two cells (76%) were excited by moving hairs and by noxious pinch, three (10%) by hair movement alone, two (7%) by noxious pinch and pressure, and for two cells (7%) no receptive field could be found. It is concluded that not only postsynaptic dorsal column neurons receive input from the spinocervical tract but also other cells in the dorsal and ventral horns and the intermediate gray matter. Possible identities for these cells are discussed.

Nucleus Z: a somatosensory relay to motor thalamus.

1. It was the aim of this study to show that nucleus Z of the cat medulla acts as a relay between the spinal cord and the ventral lateral (VL) nucleus of the motor thalamus. For this purpose, extracellular recordings were made from neurons that were antidromically identified by stimulation in the rostral thalamus, particularly VL, and orthodromically activated by electrical stimulation of the spinal cord and/or natural stimulation of the hindlimb. The electrophysiological work was complemented by anatomic work. Here, wheat germ agglutinin-horseradish peroxidase (WGA-HRP) was injected into nucleus Z and the termination sites of bulbothalamic projections were anterogradely labeled. 2. A total of 120 neurons were antidromically identified as projecting to thalamus: 101 to VL and 19 outside VL. The recording sites in nucleus Z were marked by dye injection or by electrolytic lesion. They were confined to a small region (roughly 1 mm in diameter), 2.8-3.7 mm rostral to obex, 2.9-3.8 mm lateral from the midline, and from the surface of the medulla to a depth of 1 mm. The antidromic latencies ranged between 0.8 and 3.2 ms, with no difference in latencies associated with location of neurons in nucleus Z or thalamic projection sites. 3. Injection of WGA-HRP labeled fibers and axon terminals in the contralateral thalamus. Terminal labeling was densest in the lateral parts of the mid- and caudal region of the VL nucleus and, to a lesser extent, in the adjacent rostrodorsal part of the ventro-posterior lateral (VPL) nucleus. The sites of terminal labeling in VL corresponded with location of antidromic stimulation sites. 4. Orthodromic activation of nucleus Z neurons was tested in response to electrical stimulation of the ipsilateral dorsolateral funiculus (which includes the dorsal spinocerebellar tract) and/or the dorsal columns. All neurons responded to stimulation of the dorsolateral funiculus (45/45). The responsiveness of 44 neurons was tested to stimulation of the dorsal columns. Only 8 of 44 tested responded with a discharge. The orthodromic latencies of unitary discharges ranged from 1.1 to 4.4 ms to stimulation of the dorsolateral funiculus, and from 1.1 to 4.9 ms to stimulation of the dorsal columns. Most responses are likely to be monosynaptic. Differences in latencies were not associated with location of recording sites or thalamic projection sites of nucleus Z neurons. 5. The responsiveness of many neurons (n = 84) was tested to natural stimulation of the ipsilateral hindlimb (which provides the sensory input to nucleus Z).(ABSTRACT TRUNCATED AT 400 WORDS)