Dorsolateral Funiculus Stimulation Research Articles

Electrically evoked locomotor activity in the turtle spinal cord hemi-enlargement preparation

We assessed the locomotor capacity of the left half of the spinal cord hindlimb enlargement in low-spinal turtles. Forward swimming was evoked in the left hindlimb by electrical stimulation of the right dorsolateral funiculus (DLF) at the anterior end of the third postcervical spinal segment (D3). Animals were held by a band-clamp in a water-filled tank so that hindlimb movements could be recorded from below with a digital video camera. Left hindlimb hip and knee movements were tracked while electromyograms (EMGs) were recorded from left hip and knee muscles. In turtles with intact spinal cords, electrical stimulation of the right D3 DLF evoked robust forward swimming movements of the left hindlimb, characterized by rhythmic alternation between hip flexor (HF) and hip extensor (HE) EMG discharge, with knee extensor (KE) bursts occurring during the latter part of each HE-off phase. After removing the right spinal hemi-enlargement (D8-S2), DLF stimulation still evoked rhythmic locomotor movements and EMG bursts in the left hindlimb that included HF-HE alternation and KE discharge. However, post-surgical movements and EMG bursts had longer cycle periods, and movements showed lower amplitudes compared to controls. These results show that (1) sufficient locomotor CPG circuitry resides within the turtle spinal hemi-enlargement to drive major components of the forward swim motor pattern, (2) contralateral circuitry contributes to the excitation of the locomotor CPG for a given limb, and (3) a sufficient portion of the descending DLF pathway crosses over to the contralateral cord anterior to the hindlimb enlargement to activate swimming.

Dorsal Horn Neurons Firing at High Frequency, But Not Primary Afferents, Release Opioid Peptides that Produce μ-Opioid Receptor Internalization in the Rat Spinal Cord

To determine what neural pathways trigger opioid release in the dorsal horn, we stimulated the dorsal root, the dorsal horn, or the dorsolateral funiculus (DLF) in spinal cord slices while superfusing them with peptidase inhibitors to prevent opioid degradation. Internalization of mu-opioid receptors (MOR) and neurokinin 1 receptors (NK1R) was measured to assess opioid and neurokinin release, respectively. Dorsal root stimulation at low, high, or mixed frequencies produced abundant NK1R internalization but no MOR internalization, indicating that primary afferents do not release opioids. Moreover, capsaicin and NMDA also failed to produce MOR internalization. In contrast, dorsal horn stimulation elicited MOR internalization that increased with the frequency, being negligible at <10 Hz and maximal at 500 Hz. The internalization was abolished by the MOR antagonist D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), in the presence of low Ca2+ and by the Na+ channel blocker lidocaine, confirming that it was caused by opioid release and neuronal firing. DLF stimulation in "oblique" slices (encompassing the DLF and the dorsal horn of T11-L4) produced MOR internalization, but only in areas near the stimulation site. Moreover, cutting oblique slices across the dorsal horn (but not across the DLF) eliminated MOR internalization in areas distal to the cut, indicating that it was produced by signals traveling in the dorsal horn and not via the DLF. These findings demonstrate that some dorsal horn neurons release opioids when they fire at high frequencies, perhaps by integrating signals from the rostral ventromedial medulla, primary afferents, and other areas of the spinal cord.

Metabotropic synaptic regulation of intrinsic response properties of turtle spinal motoneurones.

1. The effect of a brief train of electric stimuli in the dorsolateral funiculus on the intrinsic response properties of turtle motoneurones was investigated in transverse sections of the spinal cord in vitro. 2. Even when glutamatergic, GABAergic and glycinergic ionotropic synaptic transmission was blocked by antagonists of AMPA, NMDA, glycine and GABA receptors, dorsolateral funiculus (DLF) stimulation induced a facilitation of plateau potentials during current clamp and the underlying inward current in voltage clamp. This facilitation lasted more than 10 s. 3. The plateau potential and the facilitation by DLF stimulation was absent in the presence of 10 microM nifedipine. The DLF-induced facilitation was reduced by antagonists of 5-HT1A, group 1 metabotropic glutamate receptors and muscarine receptors. 4. These findings suggest that the intrinsic properties of spinal motoneurones are dynamically regulated by afferent synaptic activity. These afferents can be of spinal and extraspinal origin. Continuous regulation of intrinsic response properties could be a mechanism for motor flexibility.

Effects of electrical stimulation of the thoracic spinal cord on bladder and external urethral sphincter activity in the decerebrate cat

Electrical stimulation of the spinal cord above the sacral segments was used to produce coordinated micturition in the paralysed decerebrate cat. Stimulation of the superficial aspect of the dorsolateral funiculus (DLF) within the lower thoracic (T9-T13) segments produced a bladder contraction coordinated with decreased activity in the external urethral sphincter (EUS) branch of the pudendal nerve during which time fluid was expelled. In addition, a similar response was observed with DLF stimulation at the boundary of the L5/L6 segments. At the second cervical spinal segment, however, stimulation of a more lateral and ventral portion of the superficial spinal white matter was the only effective site for producing micturition. The spinal cord-evoked response was comparable to the micturition evoked by electrical stimulation of the pontine micturition centre (PMC) within the brainstem. A bilateral lesion of the dorsal columns (DC) and the dorsolateral funiculi (DLF) at the lower thoracic levels abolished reflex micturition evoked by bladder distension. However stimulation rostral to the lesion, within the PMC or thoracic DLF, continued to produce coordinated bladder and sphincter response during voiding. Stimulation caudal to the lesion produced a decrease in pudendal nerve activity but did not produce a void or bladder pressure change. This reduction in pudendal nerve activity could be abolished with a second lesion of the superficial DLF caudal to the stimulation site. It was concluded that stimulation of the thoracic dorsolateral funiculus activates both ascending and descending fibres which can influence the bladder and/or sphincter muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Descending excitation and inhibition of spinal cord lamina I projection neurons.

1. Lamina I cells were recorded in the lumbar dorsal horn of decerebrate rats. Their projecting axons were mainly located in the contralateral dorsolateral funiculus (DLF) in the upper cervical cord. 2. The effect on these cells of short and long trains of stimuli applied to the upper cervical DLF was examined by measuring the ongoing activity of the cells, their response to peripheral stimuli, and the size of their receptive fields. 3. The presence of tonic descending influences from brain stem to spinal cord was investigated by measuring the properties of the lamina I cells before and during block of descending impulses. 4. The results of DLF stimulation and of cord block show that substantial and prolonged excitation affected many cells, whereas some were inhibited for shorter periods of time. 5. The experiments were repeated with stimulation of the DLF caudal to chronic section to eliminate descending fibers. The results suggest that the changes of excitability in intact animals were partly produced by stimulation of descending fibers and partly by the invasion of collaterals activated by the antidromic stimulation of the axons projecting from the lamina I cells. 6. Although long trains of DLF stimuli generally excited lamina I cells, only inhibitions were seen in the deep dorsal horn. Moreover, stimulation rostral to an acute unilateral DLF lesion was without effect on lamina I cells but inhibited deep cells. 7. It is proposed that the lamina I cells might activate brain stem circuits, which in turn influence deep dorsal horn cells.

Relations between spinocervical and post‐synaptic dorsal column neurones in the cat.

1. In chloralose-anaesthetized cats single-unit micro-electrode recordings were made at the lumbosacral level either from axons in the dorsolateral funiculus and dorsal columns, identified as belonging to the spinocervical tract (s.c.t.) or post-synaptic dorsal column (p.s.d.c.) pathway respectively, or from neurones in the dorsal horn similarly identified. 2. Attempts were made to show that s.c.t. and p.s.d.c. neurones had axons that bifurcated, so that they sent branches into both the ipsilateral dorsolateral funiculus and the dorsal columns. That is, that some, or all, of the presumed s.c.t. or p.s.d.c. axons were common to both populations. In addition, the effects of stimuli applied to the ipsilateral dorsolateral funiculus at C3 and C1 on the resting discharges of p.s.d.c. neurones were examined in order to determine the effectiveness of the link between the s.c.t. and the p.s.d.c. pathway. 3. Thirty-three s.c.t. units (twenty-six axonal recordings and seven soma-dendritic recordings) and thirty p.s.d.c. units (twenty-four axonal and six soma-dendritic recordings) were examined for bifurcating axons by electrically stimulating the dorsolateral funiculus at C3 and the dorsal columns at C4. None of the p.s.d.c. units could be antidromically activated from the ipsilateral dorsolateral funiculus with stimulus strengths up to 40 V or seventy times threshold for antidromic activation from the dorsal columns. Similarly, twenty s.c.t. units could not be activated antidromically from the dorsal columns at stimulus strengths up to 30 V or thirty times threshold for their antidromic excitation from the dorsolateral funiculus. Thirteen s.c.t. units were antidromically activated from the cervical dorsal columns, eight at seventeen or more times threshold for their activation from the dorsolateral funiculus and five at between two and nine times threshold. All s.c.t. units that were activated antidromically from both the cervical dorsal columns and the dorsolateral funiculus showed similar latencies for the two responses. 4. Twenty-five p.s.d.c. units were examined for the effects of ipsilateral dorsolateral funiculus stimulation on their resting activity. In thirteen, clear evidence of facilitatory effects from C3 were observed, whereas similar results were seen in only six of these units when C1 was stimulated and the effects were less. The facilitation had a latency of 3-16 ms and lasted for 6-22 ms. In all but one of the twenty-five units, stimulation at both C1 and C3 produced profound inhibition of the resting discharge that began at between 8 and 26 ms and lasted for up to 300 ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Electrophysiological study of sympathoexcitatory structures of the bulbar ventrolateral surface as related to vasomotor regulation

The responses in T3–4, T10–11 and L2–3 white rami to stimulation of different zones of the bulbar ventrolateral surface were maximal when the region of about 4 mm laterally to the midline was stimulated. A weak surface stimulation of all these zones elicited only a long latency response consisting of three waves. A short latency response appeared when supramaximal stimuli were applied only to the intermediate zone—the region up to 6 mm rostrally to the hypoglossal nerve root level (zone S and caudal part of zone M). The data presented show that long and short latency responses are conducted from the intermediate zone to the spinal cord via dorsolateral funiculus fibres with a conduction velocity of about 5.6 ± 0.6m/s. In addition, a special descending sympathoexcitatory pathway oriented to T2 preganglionic neurons with a conduction velocity of about 12.3 ± 3.2m/s was demonstrated. Antidromic discharges of the output sympathoexcitatory neurons elicited by dorsolateral funiculus stimulation were found in the intermediate zone only at a depth of about 400–2000 μ M. Stimuli applied to different regions of the ipsilateral bulbar ventrolateral surface activate at least two groups of surface fibres (conduction velocities 6.7–8.0 and 2–3.2m/s) which, in turn, activate the output neurons with a rather constant delay of about 20 ms equal to a difference between the latencies of long and short latency white rami responses. The mechanism of delay formation seems to be concentrated in the intermediate zone and formed probably by a chain of interneurons. A possible scheme of neuronal organization of the bulbar ventrolateral sympathoexcitatory structures is presented and discussed. The descending tonic activation of spinal vasomotor neurons is formed by spontaneous discharges of antidromically identified output neurons with a mean firing rate of about 14.4 imp./s. Some neurons are reflexly activated within the time limits of the late somatosympathetic reflex response. Coagulation of the intermediate zone resulted in a profound fall of blood pressure, disappearance of pressor and late somatosympathetic reflexes, whereas the spinobulbospinal somatosomatic reflex remains unchanged. The baroreceptor inhibition is partly realized through the elements of sympathoexcitatory intermediate zone because the preferable inhibition of the long latency white rami response was demonstrated in the middle of R-R interval and during a sharp increase in the arterial pressure induced by vasoconstrictor drugs. Thus, the structures of the intermediate zone seem to play a key role in supporting of blood pressure level and organization of pressure reflexes. They are suggested to be the actual elements of the bulbar vasomotor center.

The functional development of descending inhibitory pathways in the dorsolateral funiculus of the newborn rat spinal cord

The postnatal development of descending inhibition in the spinal cord has been studied in the rat. Electrophysiological recordings were made in neonatal rat pups of the activity in single lumbar dorsal horn cells evoked by stimulation of the skin of the hindlimb. Descending inhibition was tested by observing the effect of stimulation of the dorsolateral funiculus (DLF) at thoracic level on the dorsal horn cell responses. In adults the DLF is known to contain descending axons from the brainstem which inhibit dorsal horn cell activity. Such inhibition was always observed in days 22–24 rat pups. At 18 days of age it was present but required higher-intensity stimulation to produce an effect. On day 12 only half the dorsal horn cells tested were inhibited by DLF stimulation and then only weakly. On day 9 no cells were inhibited. Application of horseradish peroxidase to DLF axons in the lumbar cord resulted in retrograde labelling of cells in the medulla, pons and midbrain. The labelling on day 6 was comparable to the adult. The results show that despite the early anatomical existence of a descending DLF pathway, there is no functional descending inhibition until days 10–12 of life. It is suggested that this is due to delayed maturation of crucial interneurones in the dorsal horn or to insufficient levels of 5-hydroxytryptamine or other neurochemicals in the descending DLF axon terminals.

Response of ventrobasal thalamic neurons activated by dorsal and dorsolateral funiculi: an intracellular study.

Intracellular responses to stimulation of the dorsal column (DC) and dorsolateral funiculus (DLF) were recorded in cells of the thalamic ventrobasal complex (VB) in anesthetized cats, with the dorsal funiculi either intact or isolated. The responsiveness of VB neurons was tested using graded stimulation, paired-shock, and interaction techniques. Of the 60 VB neurons thoroughly studied, 50 responded to stimulation of the DC with excitatory postsynaptic potentials (EPSPs) followed by inhibitory postsynaptic potentials (IPSPs); half of these 50 neurons responded to stimulation of the DLF with the same pattern, whereas no IPSPs could be elicited in the remaining neurons. The majority of EPSPs could be fractionated into unitary components during graded electrical stimulation. The number of such components observed was greater after DLF than after DC stimulation. In most neurons, the DLF-evoked EPSPs were smaller in amplitude than the DC-evoked EPSPs. Paired-shock stimulation facilitated the DLF excitatory responses. The amplitude of IPSPs induced by DLF stimulation was significantly smaller than that evoked by DC stimulation, and DC stimulation reduced the excitatory response to subsequent DLF stimulation. The data support the known dominance of the DC pathway in the cat.

Descending influences on receptive fields and activity of single units recorded in laminae 1, 2 and 3 of cat spinal cord

Units (108) were isolated in laminae 1,2 and 3 in segments L7-Sl of decerebrate cat spinal cord. For each unit, the size and nature of its receptive field (RF) was delineated. Then the dorsolateral funiculus (DLF) was stimulated for 1 sec with 10 or 50 Hz, 0.1 msec square waves and the response characteristics of the unit were again examined. Of the 108 units, 55 were excited or facilitated, 6 were inhibited (all in lamina 3) and 47 were unaffected. While some of the excited units responded only during the stimulus train, the majority showed prolonged excitation or facilitation lasting over one minute. The excited units were predominantly those responding to pressure or to brush, touch and pressure. Of the pressure units, 73% were excited or facilitated in contrast to only 29% of the brush/touch units. Most of the excited units showed expansion of their RFs. While many units of this type show ongoing variations of excitability and RF size, the evoked responses reported were sufficiently time-locked to the stimulus for it to be apparent that they were caused by the DLF stimulation. The unit's responses still occurred when the DLF was stimulated caudal to a complete cord transection so that the effects did not pass through the brain stem. The major effect of descending systems or of DLF stimulation previously reported on the large cells of laminae 1,4 and 5 has been inhibition. Here we report that a major descending influence on many units of laminae 1,2 and 3 is excitatory. Therefore it is suggested that a population of small interneurons in the superficial laminae could contribute to the descending inhibition of large dorsal horn neurons.

Responses of identified spinal neurones to acetylcholine applied by micro-electrophoresis.

1. The responses of identified cells in the cat Clarke's column and dorsal horn to micro-electrophoretically applied cholinomimetics and anti-cholinergic substances have been investigated. 2. Both antidromically identified (DSCT neurones) and synaptically activated neurones from the region of the Clarke's column of the spinal cord were excited by ACh. However, the proportion of ACh excited cells was greater in units synaptically activated by ipsilateral dorsolateral funiculus stimulation (78%) than in DSCT neurones (50%). In addition, about 55% of neurones activated either antidromically or synaptically by ipsilateral dorsal column stimulation were excited by ACh. 3. In contrast to a relatively weak excitatory potency on the DSCT neurones (maximum firing frequency did not exceed 130% of the control activated by ipsilateral dorsolateral funiculus stimulation (maximum firing frequency reached 430% of the control level). 4. ACh has a relatively quick and rapidly reversible excitatory effect on Clarke's column neurones and some types of dorsal horn interneurones, which can be obtained also with nicotine. However, the action of nicotine is frequently delayed in onset and recovery. This excitatory action of ACh can be blocked or markedly depressed by dihydro-beta-erythroidine. These results and those obtained with acetyl-beta-methylcholine and atropine seem to suggest that the receptors mediating excitation of the cholinoceptive spinal cells activated either antidromically or synaptically by ipsilateral dorsolateral funiculus stimulation besides predominantly nicotinic have also weak muscarinic properties. 5. Desensitization with repeated applications of ACh and nicotine has been observed in both DSCT neurones and units antidromically activated by ipsilateral dorsal column stimulation. 6. About 11% of units antidromically activated by ipsilateral dorsolateral funiculus stimulation were depressed by ACh. In addition, the depressant effect of ACh was more frequently encountered in the cells unresponsive either to the dorsolateral funiculus or dorsal column stimulation. ACh depression was also seen in units activated either antidromically or synaptically by ipsilateral dorsal column stimulation. In contrast, none of the units synaptically activated by the ipsilateral dorsolateral funiculus stimulation were depressed by ACh. The same was true for spinal neurones receiving convergent peripheral inputs activated either antidromically or synaptically by ipsilateral dorsolateral or dorsal column stimulation. 7. The findings that ACh depression of all tested DSCT neurones is blocked by atropine and readily evoked by acetyl-beta-methylcholine indicates that receptors mediating the effect are of muscarinic type.

Descending influences on spinocervical tract cell discharges evoked by non-myelinated cutaneous afferent nerve fibres

Units (180) were isolated in laminae 1, 2 and 3 in segments L7-S1 of decerebrate cat spinal cord. For each unit, the size and nature of its receptive field (RF) was delineated. Then the dorsolateral funiculus (DLF) was stimulated for 1 sec with 10 or 50 Hz, 0.1 msec square waves and the response characteristics of the unit were again examined. Of the 108 units, 55 were excited or facilitated, 6 were inhibited (all in lamina 3) and 47 were unaffected. While some of the excited units responded only during the stimulus train, the majority showed prolonged excitation or facilitation lasting over one minute. The excited units were predominantly those responding to pressure or to brush, touch and pressure. Of the pressure units, 73% were excited or facilitated in contrast to only 29% of the brush/touch units. Most of the excited units showed expansion of their RFs.While many units of this type show ongoing variations of excitability and RF size, the evoked responses reported were sufficiently time-locked to the stimulus for it to be apparent that they were caused by the DLF stimulation. The units' responses still occurred when the DLF was stimulated caudal to a complete cord transection so that the effects did not pass through the brain stem.The major effect of descending systems or of DLF stimulation previously reported on the large cells of laminae 1, 4 and 5 has been inhibition. Here we report that a major descending influence on many units of laminae 1, 2 and 3 is excitatory. Therefore it is suggested that a population of small interneurons in the superficial laminae could contribute to the descending inhibition of large dorsal horn neurons.

Propriospinal pathways in the dorsolateral funiculus and their effects on lumbosacral motoneuronal pools

Propriospinal pathways descending in the dorsolateral funiculus (DLF), which link middle lumbar with lower lumbar and sacral segments, were studied in cats in terms of effects evoked by activation of these pathways in lumbosacral motoneuronal pools. Selective activation of propriospinal fibers was achieved by preceding (12–16 days before) ipsilateral hemisection of the spinal cord in upper lumbar segments and subsequent degeneration of long descending fibers. Under such conditions stimulation of DLF evoked a mass discharge descending with a conduction velocity of about 40 m/sec in the DLF. This volley exerted a considerable conditioning influence upon monosynaptic test reflex discharges of motoneurons. Moderate DLF stimulation facilitated discharges evoked from flexor muscle afferents and inhibited discharges from extensor afferents. The duration of conditioning effects was about 15–20 msec. With increased strength of DLF stimulation secondary prolonged inhibition of both flexor and extensor reflexes was added to initial reciprocal effects. Segmental delay of propriospinal action upon motoneurons did not exceed 0.8–1.0 msec, and was identical for facilitation and inhibition. This indicates the possibility of a monosynaptic nature of both effects. DLF stimulation evoked postsynaptic potentials in motoneurons: predominantly EPSPs in flexor units and IPSPs or mixed PSPs in extensor units. Latency values of both EPSPs and IPSPs agree with the suggestion concerning the monosynaptic nature of at least part of these actions. Strong frequency potentiation is a special feature of ‘propriospinal’ PSPs. The functional significance of propriospinal pathways in DLF and their probable participation in transmission of activity from descending pathways to motoneurons are discussed.