Negative Dorsal Root Potential Research Articles

Changes in correlation between spontaneous activity of dorsal horn neurones lead to differential recruitment of inhibitory pathways in the cat spinal cord

Simultaneous recordings of cord dorsum potentials along the lumbo-sacral spinal cord of the anaesthetized cat revealed the occurrence of spontaneous synchronous negative (n) and negative-positive (np) cord dorsum potentials (CDPs). The npCDPs, unlike the nCDPs, appeared preferentially associated with spontaneous negative dorsal root potentials (DRPs) resulting from primary afferent depolarization. Spontaneous npCDPs recorded in preparations with intact neuroaxis or after spinalization often showed a higher correlation than the nCDPs recorded from the same pair of segments. The acute section of the sural and superficial peroneal nerves further increased the correlation between paired sets of npCDPs and reduced the correlation between the nCDPs recorded from the same pair of segments. It is concluded that the spontaneous nCDPs and npCDPs are produced by the activation of interconnected sets of dorsal horn neurones located in Rexed's laminae III–IV and bilaterally distributed along the lumbo-sacral spinal cord. Under conditions of low synchronization in the activity of this network of neurones there would be a preferential activation of the intermediate nucleus interneurones mediating Ib non-reciprocal postsynaptic inhibition. Increased synchronization in the spontaneous activity of this ensemble of dorsal horn neurones would recruit the interneurones mediating primary afferent depolarization and presynaptic inhibition and, at the same time, reduce the activation of pathways mediating Ib postsynaptic inhibition. Central control of the synchronization in the spontaneous activity of dorsal horn neurones and its modulation by cutaneous inputs is envisaged as an effective mechanism for the selection of alternative inhibitory pathways during the execution of specific motor or sensory tasks.

Effect of chronic undernourishment on the cord dorsum potentials and the primary afferent depolarization evoked by cutaneous nerves in the rat spinal cord

The effect of chronic undernourishment on the cord dorsum potentials (CDPs) and the dorsal root potential (DRP), closely related to primary afferent depolarization (PAD) and presynaptic inhibition in the spinal cord of the rat, was analyzed in this study. Single electrical pulses applied to the sural nerve (SU) of control ( n = 14) and chronically undernourished ( n = 16) Wistar rats produced CDPs, which are composed of four components: afferent volley (AV), two negative components (N 1 and N 2), and one positive component (P wave) and negative DRPs recorded in a small rootlet of the L6 segment of the rat. The CDPs of the control and undernourished rats with AV components of comparable amplitude (U AV/C AV = 0.96), showed N 1 components of similar amplitude ( U N 1 / C N 1 = 0.94 ), but smaller P wave (U PW/C PW = 0.23). A comparable reduction in the amplitude of the DRPs was obtained in the undernourished rats (U DRP/C DRP = 0.36). When normalized as a function of the body mass of the animals, the CDPs and DRPs produced in undernourished rats were of significantly smaller normalized amplitude than those evoked in the control. According to these results, it is suggested that chronic undernourishment induce a depressive effect on the mechanisms generating the P wave component in the CDP and the DRPs either by decreasing the sensory input and/or the excitability of the dorsal horn neurones involved in the generation of PAD and presynaptic inhibition in the spinal cord of the rat.

Dorsal horn cells connected to the lissauer tract and their relation to the dorsal root potential in the rat.

We have examined the role of dorsal horn cells that respond to Lissauer tract stimulation in regulating primary afferent depolarization (PAD). PAD was monitored by recording the dorsal root potential (DRP) in the roots of the lumbar cord. Recordings were made of the discharges of Lissauer tract-responsive cells, and their discharges were correlated with the DRPs occurring spontaneously and those evoked by stimulation. Electrical microstimulation of the Lissauer tract (<10 microA; 200 micros) was used to activate the tract selectively and evoke a characteristic long-latency DRP. Cells that were excited by Lissauer tract stimulation were found in the superficial laminae of the dorsal horn. They exhibited low rates of ongoing discharge and responded to Lissauer tract stimulation typically with a burst of impulses with a latency to onset of 5.6 +/- 2.7 ms (mean +/- SD) and to termination of 13.6 +/- 4.1 ms (n = 105). Lissauer tract-responsive cells in L5 were shown to receive convergent inputs from cutaneous and muscle afferents as they responded to stimulation of the sural nerve (100%, n = 19) and the nerve to gastrocnemius (95%, n = 19). The latency of the response to sural nerve stimulation was 3.7 +/- 1.5 ms and to gastrocnemius nerve stimulation, 8.3 +/- 3.6 ms. Stimulation through a microelectrode at a depth of 1.5 mm in the sensorimotor cortex (100 microA, 200 micros) evoked a response in 17 of 31 Lissauer tract-responsive cells (55%) with a latency to onset of 21.9 +/- 2.8 ms (n = 17). Stimulation of the sural nerve, nerve to gastrocnemius or sensorimotor cortex was shown to depress the response of Lissauer tract-responsive cells to a subsequent Lissauer tract stimulus. The ongoing discharges of Lissauer tract-responsive cells were correlated to the spontaneous DRP using spike-triggered averaging. Of 123 cells analyzed in this way, 117 (95%) were shown to be correlated to the DRP. In addition, the peaks of spontaneous negative DRPs in spinally transected animals were detected in software. Perievent time histograms triggered from these peaks showed the discharge of Lissauer tract-responsive cells to be correlated to the spontaneous DRPs in 57 of 62 cells (92%) recorded. We conclude that these data provide compelling evidence that the Lissauer tract, and the dorsal horn cells that it excites, mediate the PAD evoked from multiple neural pathways.

Five sources of a dorsal root potential: their interactions and origins in the superficial dorsal horn.

The dorsal root potential (DRP) was measured on the lumbar dorsal roots of urethan anesthetized rats and evoked by stimulation of five separate inputs. In some experiments, the dorsal cord potential was recorded simultaneously. Stimulation of the L3 dorsal root produced a DRP on the L2 dorsal root containing the six components observed in the cat including the prolonged negative wave (DRP V of Lloyd 1952). A single shock to the myelinated fibers in the sural nerve produced a DRP on the L6 dorsal root after the arrival in the cord of the afferent volley. The shape of this DRP was similar to that produced by dorsal root stimulation. Repetitive stimulation of the myelinated fibers in the gastrocnemius nerve also produced a prolonged negative DRP on the L6 dorsal root. When a single stimulus (<5 microA; 200 micros) was applied through a microelectrode to the superficial Lissauer Tract (LT) at the border of the L2 and L3 spinal segments, a characteristic prolonged negative DRP (LT-DRP) began on the L2 dorsal root after some 15 ms. Stimulation of the LT evoked DRPs bilaterally. Recordings on nearby dorsal roots showed this DRP to be unaccompanied by stimulation of afferent fibers in those roots. The LT-DRP was unaffected by neonatal capsaicin treatment that destroyed most unmyelinated fibers. Measurements of myelinated fiber terminal excitability to microstimulation showed that the LT-DRP was accompanied by primary afferent depolarization. Repetitive stimulation through a microelectrode in sensorimotor cortex provoked a prolonged and delayed negative DRP (recorded L2-L4). Stimulation in the cortical arm area and recording on cervical dorsal roots showed that the DRP was evoked more from motor areas than sensory areas of cortex. Interactions were observed between the LT-DRP and that evoked from the sural or gastrocnemius nerves or motor cortex. The LT-DRP was inhibited by preceding stimulation of the other three sources but LT stimulation did not inhibit DRPs evoked from sural or gastrocnemius nerves on the L6 dorsal root or from motor cortex on the L3 root. However, LT stimulation did inhibit the DRP evoked by a subsequent Lissaeur tract stimulus. Recordings were made from superficial dorsal horn neurons. Convergence of input from LT sural, and gastrocnemius nerves and cortex was observed. Spike-triggered averaging was used to examine the relationship between the ongoing discharge of superficial dorsal horn neurons and the spontaneous DRP. The discharge of 81% of LT responsive cells was correlated with the DRP.

Synaptic potentials of primary afferent fibers and motoneurons evoked by single intermediate nucleus interneurons in the cat spinal cord.

Spike-triggered averaging of dorsal and ventral root potentials was used in anesthetized cats to disclose possible synaptic connections of spinal interneurons in the intermediate nucleus with afferent fibers and/or motoneurons. With this method we have been able to document the existence of a distinct group of interneurons whose activity was associated with the recording of inhibitory potentials in the ventral roots (iVRPs), but not with negative dorsal root potentials (nDRPs). The iVRPs had mean durations of 60.8 +/- 22.1 ms and latencies between 1.7 and 5.1 ms relative to the onset of the interneuronal spikes. Within this group of neurons it was possible to characterize two categories depending on their responses to segmental inputs. Most type A interneurons were mono- or disynaptically activated by group I muscle afferents and polysynaptically by low threshold (1.08-1.69 X T) cutaneous fibers. Type B interneurons were instead polysynaptically activated by group II muscle and by cutaneous fibers with thresholds ranging from 1.02 to 3.1 X T. Whenever tested, both type A and B interneurons could be antidromically activated from Clarke's columns. There was a second group of interneurons whose activity was associated with the generation of both iVRPs and nDRPs. These potentials had mean durations of 107.5 +/- 35.6 and 131.5 +/- 32 ms, respectively, and onset latencies between 1.7 and 6.1 ms. The interneurons belonging to this group, which appear not to send axonal projections to Clarke's column, could be classified in three categories depending on their responses to peripheral inputs. Type C interneurons responded mono- or disynaptically to group I muscle volleys and polysynaptically to intermediate threshold (1.22-2.7 X T) cutaneous afferents. Type D interneurons were polysynaptically activated by group II muscle afferents (2.3-8.5 X T) and by intermediate threshold (1.4-3 X T) cutaneous fibers and type E interneurons only by group I muscle afferents with mono- or disynaptic latencies. A third group of interneurons produced nDRPs without iVRPs. The nDRPs had onset latencies varying from 1.9 to 6.2 ms and mean durations of 130.0 +/- 34.6 ms. These neurons (type F) showed spontaneous and evoked bursts of activity and were not antidromically activated from Clarke's column. They responded to stimulation of low- and intermediate-threshold cutaneous fibers (1.04-2.9 X T) with mono- and polysynaptic latencies, but not by group I muscle fibers. Type F interneurons appear to be located in more superficial layers than all the other interneurons.(ABSTRACT TRUNCATED AT 400 WORDS)

Presynaptic facilitatory action of locus coeruleus stimulation upon hindlimb sensory impulse transmission in decerebrate cats.

This study sought to delineate the presynaptic role of the locus coeruleus (LC) on hindlimb primary afferent terminals. Changes in presynaptic function in response to LC stimulation were assessed by measuring the dorsal root potential (DRP), interaction of LC- and peripherally-evoked DRPs, and intraspinal afferent terminal excitability. LC stimulation in unanesthetized, decerebrate cats produced a sequence of early and late positive DRPs succeeded by a small-sized negative DRP. Conditioning the negative DRPs elicited from individual hindlimb nerve branches with LC stimuli led to a decrease in test DRPs. Similarly, there was a predominant decrease in excitability in both large muscle and cutaneous afferent terminals. These data suggest a presynaptic role of the LC in augmenting afferent impulse transmission, presumably through inhibition of tonically active interneurons having axoaxonic contacts on primary afferents; functionally, presynaptic facilitation.

Identification of common interneurons mediating pre- and postsynaptic inhibition in the cat spinal cord.

The spike-triggered averaging of dorsal and ventral root potentials permits the identification of two populations of interneurons in the intermediate nucleus of the cat spinal cord. One produced negative dorsal root potentials and inhibitory ventral root potentials, in some cases with monosynaptic latencies, suggesting that they mediate presynaptic inhibition of group I afferent fibers from muscles and postsynaptic inhibition of motoneurons. The other population mediated only nonreciprocal postsynaptic inhibition of motoneurons.

Polarization of primary afferent terminals of lumbosacral cord elicited by the activity of spinal locomotor generator

The changes of electrical polarization of primary afferent terminals in the lumbosacral spinal cord have been investigated on immobilized, decorticated and spinal cats during fictive locomotion. Fictive locomotion was spontaneous or provoked by stimulation of either dorsal root or dorsal funiculi in the lumbar segments. The activation of the locomotor generator and appearance of fictive locomotion were always associated with a sustained dorsal root hyperpolarization. On the background of this positivity periodic negative dorsal root potential oscillations appeared synchronously with efferent discharges in motor hind-limb nerves. These periodic waves of primary afferent depolarization occurred in phase in different ipsilateral lumbosacral segments. On the contralateral side the periodic changes in dorsal root potential were out of phase during fictive stepping and in phase during fictive galloping. The use of Wall's technique has shown that tonic and periodic changes in dorsal root potential reflect the changes occurring in polarization of central terminals of cutaneous and muscle (Ia and Ib) groups of afferent fibres. It is concluded that the level of electrical polarization of primary afferent terminals is determined directly by the activity of the spinal locomotor generator: activation of the generator is followed by hyperpolarization of primary afferent terminals. By so modulating the polarization of afferent terminals, the locomotor generator can perform tonic and phase-dependent selection of afferent information.

The effects of convulsant doses of penicillin on primary afferents, dorsal root ganglion cells, and on ‘presynaptic’ inhibition in the spinal cord

Intracellular recordings were made from neurons in dorsal root ganglia (DRG) of rats, isolated in vitro. The depolarization of DRG cells caused by the application of gamma-aminobutyric acid (GABA) diminished reversibly when penicillin (0.08–2.0 mM) was added to the bathing fluid. The decrease of the input resistance of DRG cells measured during GABA perfusion was also depressed in the presence of penicillin, but no evidence of a shift of the reversal potential of the GABA-induced depolarization was found. Nor did penicillin (up to 10 mM) cause a change in the voltage-current function, in electrical excitability, in the inclination to repetitive firing, bursting discharge, or after discharge. In decapitate cat preparation the amplitude of the negative dorsal root potential (DRP or DR V) diminished by 0–50% after the i.v. administration of 0.5–1.0 × 10 6I.U./kg (the convulsant dose) of penicillin. Post-tetanic depression of the DRP was aggravated by penicillin. The degree of depression of the DRP bore no relationship to the promptness of the eruption, and to the intensity, of the seizure activity induced by penicillin. The rates of rise and fall of the negative DRP (DR V) were consistently slowed, the positive DRP (DR V) reduced, and the dorsal root reflex (DRR) blocked by penicillin. Inhibitory reflex effects presumed to be presynaptic were either enhanced or unchanged, never depressed by penicillin. This was seen when inhibitory function was gauged by monosynaptic reflex amplitude, and also from the inhibition of ventral root electronic excitatory postsynaptic potentials (VR EPSPs). Possible explanations of these seemingly paradoxical findings are discussed, with arguments in favor and against each.

Effect of Lissauer tract stimulation on activity in dorsal roots and in ventral roots

In decerebrate spinal cats, microelectrode stimulation of the lumbar lateral Lissauer tract (LLT), which does not spread to the dorsal roots, produces a volley in the tract that is conducted at 0.5 to 2.5 m/s. In 38 cats, such a volley in the LLT produced a negative dorsal root potential (DRP) beginning at 15 to 20 ms and lasting 30 to 40 ms, followed by a positive DRP lasting 90 to 140 ms. In seven cats, LLT stimulation produced a positive DRP alone beginning at 30 to 40 ms and lasting 80 to 110 ms. The LLT-evoked DRP was limited to the dorsal rootlets located within a few millimeters on either side of the stimulus point, unlike the dorsal root-evoked DRP. This local distribution parallels the limited spread of the LLT-evoked compound action potential. The LLT-evoked DRP occluded the dorsal root-evoked DRP. Conditioning stimuli applied to the LLT produced early facilitation and late inhibition of the monosynaptic ventral root reflex. The polysynaptic reflexes were inhibited for as long as 150 ms. With higher stimulus intensities, the polysynaptic reflexes were first inhibited and then facilitated for 150 to 1000 ms. Barbiturates first prolonged and then attenuated the LLT-evoked DRP. Picrotoxin reduced the LLT-evoked DRP but failed to have any effect on the facilitation or inhibition of the ventral root responses. Naloxone produced an enhancement of dorsal root-evoked polysynaptic reflexes. Although naloxone had no effect on the LLT facilitation of the monosynaptic reflex, it antagonized the LLT inhibition of the polysynaptic reflex.

The effects of gallamine on field and dorsal root potentials produced by antidromic stimulation of motor fibres in the frog spinal cord.

The effects of gallamine on the intraspinal field potentials and the dorsal root potentials produced by antidromic stimulation of motor fibres were studied in the isolated frog spinal cord preparation. After gallamine (10-(3) M), the duration of the negative field potential produced by antidromic activation of motoneurons (N1 response) was increased often without changing its amplitude. This resulted in an increased passive spread of the antidromic action potential towards the dorsal dendritic regions, where afferent fibres terminate. In the untreated spinal cord, stimulation of motor axons produced a late negative dorsal root potential (VR-DRP) which was depressed after gallamine administration. Abolition of the VR-DRP was frequently associated with the appearance of a short latency, conducted response, in the dorsal roots (EVR-DRP). The earliest component of the EVR-DRP had a latency ranging between 0.5 and 2.5 ms measured after the peak of the N1 response recorded at the motor nucleus. Such a brief latency of the EVR-DRP suggests that this response results from electrical interaction between motoneurons and afferent fibres. After gallamine, the primary afferent depolarization produced by orthodromic stimulation of sensory nerves facilitates the EVR-DRP without necessarily increasing the amplitude or duration of the N1 response. Also, gallamine appears to increase directly the excitability of the afferent fibre terminal arborizations. The nature of the electrical interaction between motoneuron dendrites and afferent fibre terminal arborizations is discussed in terms of two hypotheses: interaction by current flows and by electrical coupling.

A novel class of unit in the substantia gelatinosa of the spinal cat

Using platinum-tipped microelectrodes, 34 units of a kind not previously reported were found in the substantia gelatinosa of spinal, unanesthetized cats. Units were inhibited by innocuous mechanical stimuli, but after the withdrawal of such stimuli, a burst of activity lasting 5 to 20 s appeared with an initial delay (latent period) of 50 to 200 ms. In the absence of background activity, noxious stimuli had no immediate effect. However, in a period of about 20 min, units tested with noxious stimuli displayed a gradual increase in regular background firing and in the occurrence of unevoked bursts. Noxious stimuli were excitatory when applied to the units with this background activity. An approximately 1-s period of diminished activity followed withdrawal of noxious stimuli. Consecutive identical stimuli produced bursts of activity with considerable variability; latency and burst length fluctuated. Also the probability of bursts fluctuated in units with low background activity. Poststimulus time histograms showed, under some conditions, a decrease in the average number of impulses in the first 200 ms which roughly corresponded in time course to the negative dorsal root potential. It is argued that the initial latency and the decrease in activity in the histograms are temporal prolongations of the inhibitory process produced by innocuous stimuli. Moreover, based on these data, a mechanism for the generation of the negative dorsal root potential is proposed, involving dendroaxonic synaptic transmission from the substantia gelatinosa units to primary afferent terminals.

Ventral root elicited depression of the dorsal root evoked response in frog motoneurons.

Recurrent inhibition of the dorsal root (DR) evoked responses of frog motoneurons was studied by intracellular recording. Monosynaptic and early polysynaptic action potentials, as well as compound EPSPs initiated by a DR volley in motoneurons were depressed by an antidromic volley in motor axons. The depression had about 10 msec latency, reached maximum at 20-30 msec, and was maintained for 80 msec. The depression was associated with a slow, negative dorsal root potential (VR-DRP) of similar time course. No sign of recurrent postsynaptic inhibition of the motoneuron somata was found. Decrease in excitability of the motoneurons was also observed during the afterhyperpolarization (AHP) associated with either antidromic or direct spikes in the motoneurons. This excitability decrease was detectable at the time of recurrent depression of the DR-evoked responses. The data are explained by the assumption that two mechanisms are involved in the recurrent depression of the DR-evoked responses: the excitability decrease during the AHP in the motoneurons themselves, and the inhibition transmitted by a recurrent pathway which may depress the DR inputs to motoneurons presynaptically.

Functions of primary afferents and responses of extracellular K + during spinal epileptiform seizures

Paroxysmal activity in ventral roots induced by penicillin in decapitate cat spinal cord is associated with waves of depolarization of primary afferent fiber terminals. These paroxy smal depolarizations can be detected as spontaneously occurring negative dorsal root potentials (DRPs) and are associated with antidromic discharge of nerve impulses in dorsal root fibers; they can also be detected by testing the excitability of afferent nerve terminals by focal stimulation. Negative DRPs evoked by afferent nerve volleys are altered in waveform but not in amplitude during seizures induced by penicillin, although they are blocked by the administration of picrotoxin. While blocking afferent-evoked DRPs, picrotoxin does not interfere with paroxysmal DRPs, indicating differences in the generation of the two phenomena, which nevertheless have some link in common, for the paroxysmal waves occlude the evoked DRP. Such occlusion would appear as blockade, if DRPs were recorded by condenser-coupled amplifiers. In the presence of pentobarbital penicillin suppresses evoked DRPs, but under such circumstances seizure activity is not observed. Extracellular potassium activity within spinal gray matter transiently increases during seizure activity. Such increments of potassium activity are maximal in the ventral horns. This and several other observations suggest that in decapitate spinal cords systemically administered penicillin induces seizures which originate in the ventral gray matter. Accumulation of excess potassium may be the cause of paroxysmal depolarization of afferent nerve terminals. Excess potassium, while not playing a principal role in initiating seizures, may influence the course of seizures by depolarizing afferent terminals. Such depolarization probably enhances tonic background release of transmitter substance, may modify the effect of synaptic input, and may favor synchronization of waves of neural excitability through extrasynaptic mechanisms.

The effect of diazepam and picrotoxin on brainstem evoked dorsal root potentials

Diazepam has been demonstrated to have the effect of enhancing presynaptic inhibition or facilitation from supraspinal sites in cats as determined by increased negative or positive dorsal root potentials and inhibition or facilitation of the monosynaptic reflex. Experiments were performed on cats made decerebrate at the precollicular level. Dorsal root potentials were recorded from the most caudal rootlet of L6 or L7 and the monosynaptic reflex was recorded from the ventral root of L7. Stimulation was either a single shock to the gastrocnemius-soleus or common peroneal nerve or a 20msec train at 500 Hz to sites in the brainstem reticular formation. The initial negative dorsal root potentials were enhanced by diazepam regardless of origin. Diazepam also enhanced positive dorsal root potentials from the pontine reticular formation. Some pure positive dorsal root potentials from the caudal medullary reticular formation were depressed by diazepam. Picrotoxin was always found, including when diazepam depressed dorsal root potentials, to have the antagonistic action of diazepam; i.e., usually depressing the negative or positive supraspinal dorsal root potential.

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.

The role of γ-aminobutyric acid as a mediator of positive dorsal root potentials

Summary (1) A diphasic response consisting of a negative-, followed by a positive-going dorsal root potential (DRP) was evoked in L6 or L7 dorsal rootlets of unanesthetized spinal cats by 10 times group I threshold stimulation of the gastrocnemius-soleus muscle nerve. (2) The administration of 2.5 mg/kg bicuculine reversibly abolished, within 30 sec, first the negative and then the positive DRP. The time course for the recovery of the negative DRP was longer than that of the positive DRP. (3) Smaller doses of bicuculline (0.2–1.0 mg/kg) were usually much more effective against the negative than the positive DRP in terms of both magnitude and duration of suppression. (4) A selective action against the negative DRP was also observed, but with less consistency, after picrotoxin (3.0 mg/kg) administration. (5) Semicarbazide (200 mg/kg) induced a gradual diminution and often abolition of both DRPs over the course of 3 h. A selective reduction of the negative DRP occured after 60 min. (6) Suppression of the positive DRP by agents which block the receptor attachment (bicuculline and picrotoxin) and synthesis (semicarbazide) of GABA suggests that GABA is a transmitter in the pathway(s) mediating primary afferent hyperpolarization. (7) The possibility that GABA synapses occur in each of two separate pathways leading to the afferent terminal is discussed. According to this model, the positive DRP represents the GABA-mediated inhibition of a tonic non-GABA-mediated PAD; the negative DRP is conducted through a separate pathway terminating in a GABA-mediated axo-axonic synapse. The differential susceptibility would reflect, according to this model, anatomical or physiological differences between the GABA synapses of the respective pathways.

Bicuculline and Picrotoxin Blockade of Positive Dorsal Root Potentials

MOUNTING evidence suggests that GABA functions as a transmitter in the pathways mediating presynaptic inhibition in the spinal cord1–10 and cuneate nucleus11–14. In spite of recent attempts to locate a GABA synapse in these multi-synaptic pathways at the axo-axonic terminal4,13,15, the clarification of GABA's role in this system awaits the elucidation of the complex circuits mediating afferent terminal polarization. This complexity may include such features as tonic activity of interneurones and convergence of phasic inputs from different fibre groups. For example, Mendell16, recording spinal cord dorsal root potentials (DRPs), has observed that stimulation of high threshold afferent fibres from muscle nerve generates a positive going DRP, reflecting primary afferent hyperpolarization. From studies of the interactions between positive and negative DRPs he has postulated that the positive DRP results from a phasic inhibition of tonic activity in the pathway for the negative DRP17. This implies that the axoaxonic synapse is common to the pathways for both the positive and negative DRPs. Thus, if the only GABA synapse in this system is located at the axo-axonic junction, antagonists of GABA should block DRPs of both polarities.

Properties and distribution of peripherally evoked presynaptic hyperpolarization in cat lumbar spinal cord.

1. The action of peripheral nerve volleys on the polarization of presynaptic terminals of inactive sensory fibres in cat lumbar spinal cord has been investigated by recording (a) the dorsal root potential (DRP), (b) intracellular changes in polarization of single preterminal axons (PAD or PAH), and (c) changes in excitability of populations of preterminal axons.2. Presynaptic hyperpolarization (positive DRP-PAH) can be evoked by stimulation of muscle group III afferents as well as by volleys in cutaneous Abeta, Adelta and C afferents. These volleys can also produce presynaptic depolarization (negative DRP-PAD).3. The positive DRP is observed in the decerebrate state and increases in amplitude following spinalization.4. Picrotoxin blocks the positive DRP at the same dosages required to block the negative DRP. Test negative DRPs are depressed during a conditioning positive DRP. These results are used to support earlier suggestions that the positive DRP results from inhibition of interneurones mediating the negative DRP.5. Trains of group III stimuli at 20/sec evoke a steady positive DRP. Trains of the same intensity at 200/sec evoke a phasic negative DRP. This frequency dependence is observed for PAD and PAH in single sensory axons.6. The DRPs recorded from different dorsal root filaments in response to a given stimulus vary widely in the ratio of negative to positive DRP.7. Intracellular recording from single axons reveals that the same stimuli evoke widely varying ratios of PAD and PAH.8. Stimulation of FRA evokes PAH > PAD in PBST group I afferents, PAD > PAH in sural A fibres and intermediate effects in G-S group I units.9. It is suggested that activation of flexor reflex afferents may selectively potentiate the synaptic efficacy of large muscle afferents mediating the flexor reflex rather than large skin afferents or large afferents from extensor muscles.

Cerebellar Control of the Vestibular Pathways to Spinal Motoneurons and Primary Afferents

Publisher Summary This chapter shows that stimulation of the fastigial nucleus produces not only contraction of the extensor muscles, but also negative dorsal root potentials (DRPs) in the lumbar cord. These DRPs are because of depolarization of the terminal arborizations of the primary afferents and involve the group Ia pathway from both extensor and flexor muscles and the cutaneous afferents. The fastigial influence on the extensor muscles is mediated via the lateral vestibular nucleus, which is known to exert a facilitatory influence on the extensor motoneurons. On the other hand, the medial vestibular nucleus is in the transmission of the fastigial influence on primary afferents. Stimulation of the vermal cortex of the cerebellar anterior lobe with the same intensities, which inhibit the decerebrate rigidity, may evoke positive DRPs in the lumbar cord. The same stimulation is also able to suppress the depolarization in the group Ia muscle and the cutaneous afferents elicited by stimulation of the VIII nerve. It appears that neurons in the lateral and the medial vestibular nuclei influence the motoneurons and the primary afferents respectively, therefore, it is concluded that the cerebellar inhibitory control of the vestibular reflex path to motoneurons is exerted through the lateral vestibular nucleus, while the cerebellar inhibitory control of the vestibular reflex path to primary afferents is exerted through the medial vestibular nucleus.