Inhibition of dorsal column by nuclei stimulation of trigeminal afferents in decerebrate—decerebellate cats

In decerebrate—decerebellate cats, stimulation of trigeminal afferents inhibited neurons in dorsal column (DC) nuclei driven by activation of DC input and produced primary afferent depolarization in DC primary afferent terminals. This inhibition was most likely mediated by a trigeminal—brainstem—DC nuclear loop.     

Characteristics of dorsal neck muscle afferent input to the cat frontal cortex before and after dorsal funiculus section

Electrical stimulation of a nerve branch to the biventer cervicis and complexus and of the suboccipital nerve to the rectus capitis dorsalis major and obliquus capitis caudalis muscles of the cat dorsal neck evoked field and single-cell activity in the frontal cortex at latencies of 5 to 46 ms. Inhibitory effects were also observed. Approximately 20% of the cells tested received their afferent input from electrophysiologically characterized group I afferent fibers, determined by recording threshold afferent volleys from the first and second dorsal rootlets. These cells had the shortest latencies (5 to 10 ms) and followed stimulus frequencies to as much as 2 Hz. The remainder of the neurons required intensities of stimulation greater than 1.5 times threshold for activation, and followed stimulus frequencies of 0.5 Hz or less. After unilateral dorsal funiculus transection, early evoked cell and field activity dependent on stimulation intensities of 1.1 to 1.3 times threshold was abolished in the contralateral frontal cortex. However, nerve stimulation with intensities of 1.8 to 3 times threshold was still effective in eliciting neuronal responses. Significant increase in mean cell latency was observed in coronal, in presylvian, and on the dorsal, but not the ventral, bank of the cruciate sulcus after the lesion. The results showed that the dorsal funiculus lesion resulted in selective removal of group I afferent input from the dorsal neck to the contralateral frontal cortex.     

Control of Impulse Conduction in Long Range Branches of Afferents by Increases and Decreases of Primary Afferent Depolarization in the Rat

It has been shown previously that impulses in axons of the descending branches of myelinated afferents in rat dorsal columns may suffer a blockade of transmission along their course in the dorsal columns. This paper tests the effect of the mechanism of primary afferent depolarization on the orthodromic movement of impulses in descending dorsal column primary afferent axons originating in the L1 dorsal root. Orthodromic impulses were recorded in the L5 and 6 dorsal columns after stimulation of the L1 dorsal root. Twenty-seven out of 82 axons (33%) suffered a temporary transmission block if primary afferent depolarization had been induced by L5 stimulation before the L1 stimulus. The tendency to block peaked at 10–15 ms and persisted for up to 30–40 ms. The number of single unit orthodromic impulses originating from the L1 root and recorded during a search of the dorsal columns 15 mm caudal to L1 increased by a factor of 3.1 after the systemic administration of bicuculline (1 mg/kg). The number of single unit orthodromic impulses originating from the L1 root and recorded in axons descending in the dorsal columns 20 mm caudal to the root increased by a factor of 8.7 after the systemic administration of picrotoxin (5 mg/kg). It is concluded that the transmission of impulses in the long range caudally running axons from dorsal roots to dorsal columns may be blocked during primary afferent depolarization and that conduction may be restored by the administration of GABA antagonists.     

The possibility of different effects of primary afferent depolarization on spinal reflexes]

Intensive depolarization of central primary afferent terminals evoked by strong stimulation of afferent nerves or dorsal root produces recurrent discharges which may be recorded as antidromic dorsal root reflexes. It is shown that the discharges are simultaneously propagating in the dorso-ventral direction and thus produce facilitation of spinal reflexes. The obtained results allow suggesting the existence of two types of influences of the primary afferent depolarization on the reflex transmission to the spinal cord.     

Evidence that some long‐lasting effects of direct current in the rat spinal cord are activity‐independent

The effects of trans‐spinal direct current (DC) stimulation (tsDCS) on specific neuronal populations are difficult to elucidate, as it affects a variety of neuronal networks. However, facilitatory and depressive effects on neurons processing information from the skin and from muscles can be evaluated separately when weak (0.2–0.3 μA) DC is applied within restricted areas of the rat spinal cord. The effects of such local DC application were recently demonstrated to persist for at least 1 h, and to include changes in the excitability of afferent fibres and their synaptic actions. However, whether these effects require activation of afferent fibres in spinal neuronal pathways during DC application, i.e. whether they are activity‐dependent or activity‐independent, remained an open question. The aim of the present study was to address this question by analysing the effects of local DC application on monosynaptic actions of muscle and skin afferents (extracellular field potentials) and afferent fibre excitability. The results revealed that long‐lasting post‐polarization changes evoked without concomitant activation of afferent fibres replicate changes evoked by stimuli applied during, before and after polarization. The study leads to the conclusion that the reported effects are activity‐independent. As this conclusion applies to the local effects of DC application in at least two spinal pathways and to the effects of both cathodal and anodal polarization, it indicates that some of the more widespread effects of trans‐spinal and trans‐cranial stimulation (both tsDCS and transcranial DC stimulation) may be activity‐independent. The results may therefore contribute to the design of more specific DC applications in clinical practice.     

Presynaptic modulation of synaptic effectiveness of afferent and ventrolateral tract fibers in the frog spinal cord

In the isolated frog spinal cord, antidromic stimulation of motor nerves produces intraspinal field potentials with a characteristic spatial distribution. When recording from the ventral horn, there is a short latency (1–2 msec) response corresponding to activity generated by antidromic activation of motoneuron cell bodies and proximal dendrites. In addition, in the dorsal horn, a delayed wave (12–13 msec latency) corresponding in time with the negative dorsal root potential is also recorded. This wave (VR-SFP) is positive at the dorsal surface of the cord and inverts to negativity at more ventral regions. The negative VR-SFP is maximum between 300–500 μm depth from the dorsal surface and decays with increasing depth towards the motor nucleus. Six days after chronic section of the dorsal roots L7 to L9 in one side of the spinal cord, stimulation of the motor nerves on the deafferented side produces only the early response attributable to antidromic activation of motoneurons. No distinctive VR-SFPs are recorded at any depth within the cord. These findings are consistent with the interpretation that afferent fiber terminals are the current generators of the VR-SFP. The presynaptic and postsynaptic focal potentials recorded in the motor nucleus after stimulation of the ventrolateral tract, as well as the corresponding synaptic potentials electrotonically recorded from the ventral roots, are not depressed during conditioning stimulations which produce primary afferent depolarization. This contrasts with the depression of the presynaptic and post-synaptic focal potentials and synaptic potentials produced by stimulation of sensory fibers. It is concluded that, unlike the afferent fiber terminals, the terminals of the ventrolateral tract are not subjected to a presynaptic modulation of the type involving primary afferent depolarization.     

Ventral root potentials of the cat's sacrococcygeal segments evoked by stimulation of intact and transected dorsal roots

The latency and amplitude of reflex-evoked potentials in the sacrococcygeal ventral roots of acute spinalized cats were investigated. The characteristics of the potentials were examined in response to electrical stimulation of intact and acutely transected dorsal roots. We found that: the last sacral and caudal (coccygeal) segments of the cat's spinal cord are endowed with electrophysiologic characteristics that distinguish them from other spinal segments (e.g., L7-S1); afferent stimulation of the corresponding intact dorsal roots evokes in the ventral root of segment S2 a small monosynaptic response, whereas no monosynaptic response is seen in segment Ca6; acute transection of the dorsal roots provokes an increment of the monosynaptic response in all segments studied except for Ca6; rhizotomy provokes in Ca5 the appearance of polysynaptic responses to electrical stimulation of the corresponding dorsal root; and transection of the cutaneous afferent fibers of the coccygeal motoneurons resulted in an increment of monosynaptic and polysynaptic responses, indicating the removal of inhibitory effects.     

Many ventral root afferent fibers in the cat are third branches of dorsal root ganglion cells

The arrangement of the ventral root afferent fibers was investigated in anesthetized and paralyzed cats. Single unit activity was recorded from a fascicle of the distal stump of the cut S1 dorsal root. Activity was elicited by stimulating the distal stump of the cut S1 ventral root. Attempts were then made to collide this activity with that elicited by stimulation of the S1 spinal nerve. Single unit activity elicited by ventral root stimulation was recorded from a total of 33 axons. In 17 of these, the activity collided with that elicited by peripheral stimulation. These results indicate that more than half the sampled population of ventral root afferent fibers are branches of dorsal root ganglion cells that have at least 3 processes: one in the dorsal root, one in the ventral root and one in a peripheral nerve. In 10 of these units, the conduction velocity of each of 3 processes was determined using the collision technique. The conduction velocities differed in the processes of a given ganglion cell, with conduction in the ventral root process generally being the slowest. The change in conduction velocity along the length of the ventral root was examined by comparing latency differences for the unit activity elicited by ventral root stimulation at different sites in the same root separated by known distances. The conduction velocity was found not to be uniform along the course of the ventral root. In many cases, the conduction velocity slowed down as the fiber approached the spinal cord. We conclude from the present study that many ventral root afferent fibers are the third branches of dorsal root ganglion cells that also have processes in the dorsal root and in a peripheral nerve. The sizes of each of these 3 processes of the dorsal root ganglion cell may differ; the ventral root process tends to be the smallest and is usually unmyelinated. Furthermore, many of the ventral root afferent fibers may taper as they approach the spinal cord.     

Stimulation of the MLR inhibits the discharge of dorsal horn neurons responsive to muscular contraction

We found that electrical stimulation of the mesencephalic locomotor region (MLR) inhibited the discharge of deep dorsal horn neurons receiving group III afferent input from the triceps surae muscles. In contrast, contraction of these muscles induced by electrical stimulation of the tibial nerve activated these dorsal horn neurons. Our findings show that descending central motor commands can inhibit dorsal horn interneurons receiving input from group III afferents during exercise.     

Tuning of spinal networks to frequency components of spike trains in individual afferents

Cord dorsum potentials (CDPs) evoked by primary afferent fiber stimulation reflect the response of postsynaptic dorsal horn neurons. The properties of these CDPs have been shown to vary in accordance with the type of primary afferent fiber stimulated. The purpose of the present study was to determine the relationships between frequency modulation of the afferent input trains, the amplitude modulation of the evoked CDPs, and the type of primary afferent stimulated. The somata of individual primary afferent fibers were impaled in the L7 dorsal root ganglion of alpha-chloralose-anesthetized cats. Action potentials (APs) were evoked in single identified afferents via the intracellular microelectrode while simultaneously recording the response of dorsal horn neurons as CDPs, or activity of individual target interneurons recorded extracellularly or intracellularly. APs were evoked in afferents using temporal patterns identical to the responses of selected afferents to natural stimulation of their receptive fields. Two such physiologically realistic trains, one recorded from a hair follicle and the other from a slowly adapting type 1 receptor, were chosen as standard test trains. Modulation of CDP amplitude in response to this frequency-modulated afferent activity varied according to the type of peripheral mechanoreceptor innervated. Dorsal horn networks driven by A beta afferents innervating hair follicles, rapidly adapting pad (Krause end bulb), and field receptors seemed "tuned" to amplify the onset of activity in single afferents. Networks driven by afferents innervating down hair follicles and pacinian corpuscles required more high-frequency activity to elicit their peak response. Dorsal horn networks driven by afferents innervating slowly adapting receptors including high-threshold mechanoreceptors exhibited some sensitivity to the instantaneous frequency, but in general they reproduced the activity in the afferent fiber much more faithfully. Responses of synaptically coupled dorsal horn neurons belonging to either hair follicle or SA1 fiber-driven networks to frequency-modulated input were in agreement with the CDP results, confirming that CDP amplitude modulation is a true reflection of EPSP amplitude modulation in at least a subset of dorsal horn neurons comprising the network.     

Increased renal interstitial hydrostatic pressure causes c-fos expression in the rat''s spinal cord dorsal horn

To describe a sympathetic afferent circuit, interstitial hydrostatic pressure in the left kidney was increased in anesthetized rats for 1.5 h to activate renal mechanoreceptor afferents. Following renal afferent stimulation, the number of immunocytochemically stained cells for the immediate early gene c-fos was increased within the dorsal horn of the spinal cord. Relative to the surgical control procedure, increasing renal interstitial hydrostatic pressure produced more immunocytochemically stained cells per tissue section in laminae I and II of the dorsal horn both ipsilateral and contralateral to the stimulated kidney in the three most caudal thoracic spinal segments. Further, the number of c-fos immunocytochemically stained cells per section in the dorsal horn ipsilateral to the stimulated kidney was 28% greater than the number of stained cells contralateral to it. The staining patterns in the dorsal horns of stimulated and control animals were similar with most labeled cells in laminae I and II. These results indicate that (1) c-fos immunocytochemical staining may be useful for tracing specific sympathetic afferent pathways, (2) sensory pathways affected by increased renal interstitial hydrostatic pressure include spinal neurons located at lower thoracic levels, and (3) some of this sympathetic afferent pathway is located contralateral to the stimulated kidney. Neurons in the contralateral dorsal horn activated by renal stimulation may mediate renorenal reflexes.     

Depression of afferent-induced primary afferent depolarization at the lumbar spinal cord following concussive head injury

Afferent-induced primary afferent depolarization (PAD) was depressed for 2-5 min following concussive head injury in the cat, as assessed by dorsal root potentials and augmentation of antidromic dorsal root potentials, both evoked by stimulation of adjacent dorsal roots. These changes in PAD were abolished by spinal cord transection but not affected by midpontine transection. Spontaneous dorsal root potentials, resting amplitudes of antidromic dorsal root potentials and reductions of antidromic dorsal root potentials following tetanic root stimulation were not substantially altered by injury. These findings suggest that concussive head injury depresses spinal interneuronal transmission by neurally mediated processes involving the bulbar brainstem.     

The effects of electrical stimulation of A and C visceral afferent fibres on the excitability of viscerosomatic neurones in the thoracic spinal cord of the cat

Single unit electrical activity has been recorded from viscerosomatic neurons in the lower thoracic spinal cord of decerebrate spinalized cats. The responses of the cells to electrical stimulation of afferent fibres in the splanchnic (SPLN) nerve and the effects of repetitive stimulation of somatic and visceral afferent C-fibres have been studied. Four groups of viscerosomatic neurones could be distinguished according to the type of visceral afferent input of the cells: (1) A-only cells (32.9%), driven only by stimulation of A delta afferent fibres in the SPLN nerve; (2) C-only cells (3%), driven only by stimulation of C afferent fibres in the SPLN nerve; (3) A + C cells (45.7%), driven by both A delta and C afferent fibres in the SPLN nerve; and (4) A + C? cells (18.6%), driven by A delta visceral afferents and showing signs of responsiveness to C-fibres though lacking a distinct response volley to visceral C-fibre activation. Two cells of the A + C group and located in lamina I of the dorsal horn responded to SPLN nerve stimulation in a manner consistent with the afferent fibre composition of the nerve, that is, showed evidence of strong monosynaptic links with SPLN afferent C-fibres and weaker responses to SPLN A delta afferents. Excitability changes of viscerosomatic neurones ('wind up', 'wind down' and changes in background activity) were also observed in the majority of neurones following electrical stimulation of somatic and of visceral afferent C-fibres.(ABSTRACT TRUNCATED AT 250 WORDS)     

Laminar distributions of 2-deoxyglucose uptake in the rat spinal cord following electrical stimulation of the sciatic nerve

The 2-deoxyglucose method was employed to study the functional organization of afferent axons in the dorsal horn of the rat spinal cord. Stimulation of axons in the sciatic nerve with conductionvelocities > 17m/s produced activity predominantly in the deep laminae of the dorsal horn. In contrast, stimulation of the entire population produced activity throughout the dorsal horn. The results are discussed in relation to the functional organization of the rat dorsal horn.     

Role of cervical neurons in propriospinal inhibition of thoracic dorsal horn neurons.

We previously reported that electrical or glutamate stimulation of the cervical spinal cord elicits a 40-60% decrease in renal sympathetic nerve activity (RSA) in the anesthetized rats. This sympatho-inhibition was possible, however, only after transection of the spinal cord at C1 or GABAergic inhibition of neurons in the rostral ventrolateral medulla. We postulated that cervical neurons inhibit RSA by inhibiting the activity of spinal interneurons that are antecedent to sympathetic preganglionic neurons (SPNs), and that these interneurons may be, in turn, excited by afferent signals. In this study, we tested the hypothesis that cervical neurons can inhibit visceroceptive thoracic spinal neurons. We recorded the spontaneous and evoked activity of 45 dorsal horn neurons responsive to splanchnic stimulation before, during, and after chemical or electrical stimulation of the cervical spinal cord in chloralose-anesthetized spinal rats. Cervical spinal stimulation that inhibited RSA also inhibited the spontaneous and/or evoked activity of 44 dorsal horn neurons. In addition to inhibiting splanchnic-evoked neuronal responses, cervical stimulation also inhibited responses, in the same neurons, evoked by noxious heat or light brushing of receptive dermatomes. We concluded that cervical neurons participate in propriospinal inhibition of afferent transmission and that this inhibitory system may be involved in controlling the access of afferent information to SPNs.     

Dynorphin A: in vivo release in the spinal cord of the cat

The antibody microprobe technique was used to study the release of immunoreactive dynorphin A within the lower lumbar spinal cord of anaesthetised cats. A basal release was observed in the dorsal horn, centered in the region of lamina I, but was abolished by spinal cord transection at the thoracolumbar junction. Release of dynorphin A in the lamina I region was evoked by high-frequency electrical stimulation of unmyelinated primary afferent fibres, whereas stimulation of myelinated (including A delta) afferents was ineffective. Evidence was also obtained for release in laminae V-VI and at the spinal cord surface. These results suggest that in the lumbar spinal cord of the cat, dynorphin A is released in the superficial dorsal horn by impulses in descending pathways and in somatic unmyelinated primary afferent fibres.     

Intra-axonal recordings in rat dorsal column axons: membrane hyperpolarization and decreased excitability precede the primary afferent depolarization

Intra-axonal recordings were obtained in the dorsal columns of the rat lumbosacral spinal cord. Dorsal root or dorsal column stimulation at levels subthreshold for the impaled axon elicited a prolonged depolarization corresponding to the primary afferent depolarization (PAD). The depolarization was preceded by a brief hyperpolarizing potential during which excitability was decreased. The hyperpolarization corresponds temporally to the extracellularly recorded DRP IV component of the dorsal root potential described by Lloyd and McIntyre, and may represent the intracellular correlate of this potential. Possible mechanisms for this hyperpolarization include electrical interactions between neuronal elements, a biphasic GABA response, or attenuation of background afferent axonal depolarization.     

The spinal course and medullary termination of myelinated renal afferents in the rat

Myelinated afferent fibers, recorded in the left renal nerve of rats, were antidromically activated by discrete electrical stimulation of the cervical spinal cord and the caudal medulla. The lowest thresholds for activation of these fibers were found in the most medial portion of the ipsilateral fasciculus gracilis. This region of minimum threshold continued rostrad through the nucleus commissuralis. Based on threshold vs depth contours, fibers appeared to terminate in the ipsilateral nucleus gracilis and nucleus solitarius. Myelinated fibers could be activated by punctate pressure on the renal hilus. Action potentials generated by hilar pressure collided with antidromically-conducted action potentials elicited by electrical stimulation at cervical levels. We conclude that myelinated renal afferents carry information from intrarenal receptors, via the dorsal column system, to both visceral afferent and dorsal column nuclei.     

Olfactory ensheathing cell grafts have minimal influence on regeneration at the dorsal root entry zone following rhizotomy

The effectiveness of grafts of olfactory ensheathing cells (OECs) as a means of promoting functional reconnection of regenerating primary afferent fibers was investigated following dorsal root injury. Adult rats were subjected to dorsal root section and reanastomosis and at the same operation a suspension of purified OECs was injected at the dorsal root entry zone and/or into the sectioned dorsal root. Regeneration of dorsal root fibers was then assessed after a survival period ranging from 1 to 6 months. In 11 animals, electrophysiology was used to look for evidence of functional reconnection of regenerating dorsal root fibers. However, electrical stimulation of lesioned dorsal roots failed to evoke detectable cord dorsum or field potentials within the spinal cord of any of the animals examined, indicating that reconnection of regenerating fibers with spinal cord neurones had not occurred. In a further 11 rats, immunocytochemical labeling and biotin dextran tracing of afferent fibers in the lesioned roots was used to determine whether regenerating fibers were able to grow into the spinal cord in the presence of an OEC graft. Although a few afferent fibers could be seen to extend for a limited distance into the spinal cord, similar minimal in-growth was seen in control animals that had not been injected with OECs. We therefore conclude that OEC grafts are of little or no advantage in promoting the in-growth of regenerating afferent fibers at the dorsal root entry zone following rhizotomy.     

Inhibition of nociceptive withdrawal flexion reflexes through a dorsal column-brainstem-spinal loop

In decerebrate-decerebellate cats, dorsal column stimulation (DCst) rostral to dorsal funicular cuts, to prevent antidromic activation of afferent dorsal column fibers, inhibited spinal flexion reflexes evoked by nociceptive stimuli. The effects of DCst above the cuts were compared to those below the cuts. Our findings indicate that the analgesic effects of DCst can be attributed to activation of a DC-brainstem-spinal loop in addition to antidromic activation of spinal 'gating' mechanisms.