Antidromic Impulses Research Articles

Interaction and adiabatic evolution of orthodromic and antidromic impulses in the axoplasmic fluid

Unlike expected from the Hodgkin-Huxley model predictions, in which there is annihilation once orthodromic and antidromic impulses collide, the Heimburg-Jackson model demonstrates that both impulses penetrate each other as it has been shown experimentally. These impulses can be depicted as low amplitude nonlinear excitations in a weakly dissipative soliton model described by the damped nonlinear Schrödinger equation. In view of the above, the Karpman-Maslov-Solov'ev perturbation theory turns out to be ideal to study the interaction and adiabatic evolution of orthodromic and antidromic impulses once axoplasmic fluid is present.

Short-term inhibition of spinal reflexes in multiple lower limb muscles after neuromuscular electrical stimulation of ankle plantar flexors.

Neuromuscular electrical stimulation (NMES) of lower limbs elicits muscle contractions through the activation of efferent fibers and concomitant recruitment of afferent fibers, which can modulate excitability of the central nervous system. However, neural mechanisms of NMES and how unilateral stimulation of the soleus affects spinal reflexes in multiple lower limb muscles bilaterally remains unknown. Twelve able-bodied participants were recruited, and spinal reflex excitability changes were tested after four interventions, each applied for 60s, on the right plantar flexors: (1) motor-level NMES; (2) sensory-level NMES; (3) voluntary contraction; (4) rest. Spinal reflexes were elicited using single-pulse transcutaneous spinal cord stimulation applied on the lumbar level of the spinal cord to evoke bilateral responses in multiple lower limb muscles, while maximum motor response (Mmax) was tested in the soleus by stimulating the posterior tibial nerve. Spinal reflexes and Mmax before each intervention were compared to immediately after and every 5min subsequently, for 15min. Results showed that motor-level NMES inhibited spinal reflexes of the soleus and other studied muscles of the ipsilateral leg, but not the contralateral leg (except vastus medialis) for 15min, while not affecting soleus muscle properties (Mmax). Voluntary contraction effect lasted less than 5min, while sensory-level NMES and rest did not produce an effect. Short-term spinal reflex excitability was likely affected because antidromic impulses during motor-level NMES coincided in the spinal cord with afferent inputs to induce spinal neuroplasticity, whereas afferent input alone did not produce short-term effects. Such activation of muscles with NMES could reduce spasticity in individuals with neurological impairments.

Investigation of anodal stimulation and its implications for F-wave examinations.

Recent studies have shown that stimulation occurs at the anode of stimulating electrodes instead of anodal block. This phenomenon may be a pitfall in F-wave examinations. Subjects included 10 healthy volunteers. Their ulnar nerve was stimulated at the wrist with the cathode placed distally. Antidromic impulses were evaluated using mixed nerve action potential (MNAP) at the elbow. Anodal stimulation occurred for both sensory and motor fibers at 22 mm proximal to the anode, on average, which may theoretically shorten the F-wave latency by about 0.8 ms. Displacement of the anode away from the nerve made anodal stimulation less likely. In contrast, displacement of the cathode away from the nerve lowered the threshold for anodal stimulation, a newly found interaction between cathode and anode. In this work we identified detailed features of anodal stimulation and potential influence on F-wave examinations. Muscle Nerve 56: 51-56, 2017.

Another Perspective on Fasciculations: When is it not Caused by the Classic form of Amyotrophic Lateral Sclerosis or Progressive Spinal Atrophy?

Fasciculations are visible, fine and fast, sometimes vermicular contractions of fine muscle fibers that occur spontaneously and intermittently. The aim of this article is to discuss the main causes for fasciculations and their pathophysiology in different sites of the central/peripheral injury and in particular to disprove that the presence of this finding in the neurological examination is indicative of amyotrophic lateral sclerosis. Undoubtedly, most fasciculations have a distal origin in the motor nerve both in normal subjects and in patients with motor neuron disease. Most of them spread to other dendritic spines often producing an antidromic impulse in the main axon. The clinical and neurophysiological diagnosis must be thorough. It may often take long to record fasciculations with electroneuromyography. In other cases, temporal monitoring is necessary before the diagnosis. The treatment, which may be adequate in some cases, is not always necessary.

Efferent Fibers Innervate Gustatory and Mechanosensitive Afferent Fibers in Frog Fungiform Papillae

A possibility of efferent innervation of gustatory and mechanosensitive afferent fiber endings was studied in frog fungiform papillae with a suction electrode. The amplitude of antidromic impulses in a papillary afferent fiber induced by antidromically stimulating an afferent fiber of glossopharyngeal nerve (GPN) with low voltage pulses was inhibited for 40 s after the parasympathetic efferent fibers of GPN were stimulated orthodromically with high voltage pulses at 30 Hz for 10 s. This implies that electrical positivity of the outer surface of papillary afferent membrane was reduced by the efferent fiber-induced excitatory postsynaptic potential. The inhibition of afferent responses in the papillae was blocked by substance P receptor blocker, L-703,606, indicating that substance P is probably released from the efferent fiber terminals. Slow negative synaptic potential, which corresponded to a slow depolarizing synaptic potential, was extracellularly induced in papillary afferent terminals for 45 s by stimulating the parasympathetic efferent fibers of GPN with high voltage pulses at 30 Hz for 10 s. This synaptic potential was also blocked by L-703,606. These data indicate that papillary afferent fiber endings are innervated by parasympathetic efferent fibers.

The Effect of Blocking of Antidromic Impulses by Capsaicin on Mechanical Allodynia in a Rat Model of Peripheral Neuropathic Pain

Background: Nerve impulses that are generated in injured nociceptive fibers and enter the spinal cord are known to cause central sensitization leading to neuropathic pain. Injury-induced impulses that are transmitted antidromically into the peripheral terminals of nociceptive fibers may also cause nociceptors to be sensitized, thus contributing to neuropathic pain. However, this possibility has not yet been tested. The present study was designed to investigate the effects of antidromic impulses on the mechanical allodynic behavior seen in a rat model of neuropathic pain. Methods: Male Sprague-Dawley rats were assigned randomly into one of two groups, i.e., a capsaicin group or a vehicle group. Capsaicin group animals were treated with 1% capsaicin (4) in the stump of the distal nerve after severing the fifth left lumbar spinal nerve in order to inhibit delayed and continued antidromic impulses. The vehicle group was treated with same solution without capsaicin. The withdrawal threshold for mechanical allodynia was measured using von Frey hairs in terms of the bending force required to elicit hind-paw withdrawal. Threshold values were compared between the two groups. Results: The capsaicin group showed a statistically significant difference in terms of the paw withdrawal threshold as compared with the corresponding control from 12 days and this remained so until 32 days after treatment. Conclusions: Our results suggest that antidromic impulses developed by nerve injury are partly responsible for the development of mechanical allodynia.

Functional Electrical Stimulation and rehabilitation—an hypothesis

Functional Electrical Stimulation (FES), used to mimic a weak or paralysed movement, sometimes is followed by a specific recovery of voluntary power in that movement. The mechanism by which this occurs is unclear, and the presumption has often been that FES may somehow promote adaptive changes in cortical connectivity. However, the unique feature of electrical stimulation is that it activates nerve fibres both orthodromically and antidromically. The antidromic impulse in motor nerve fibres will reach the anterior horn cell, but it can go no further up the neuraxis. If the corticospinal-anterior horn cell synapse is a Hebb-type modifiable synapse (i.e. one that is strengthened by the coincidence of presynaptic and postsynaptic activity), then FES, combined with coincident voluntary effort through a damaged pyramidal motor system, could help to promote restorative synaptic modifications at anterior horn cell level, by this unique adaptive mechanism.

顔面神経麻ひの電気的診断法

Electrical examinations for the diagnosis of facial palsies are reviewed. Because the recovery of nerve function is prescribed by the degree of wallerian degeneration and the degenerated nerve fibers are not responsive to stimulation, the examinations using electrical stimulation are important for the accurate prognostic diagnosis of facial palsy.Because of its simplicity and convenience, the nerve excitability test (NET) is the most popular in clinical use. But its reliability is insufficient. Electroneurography (ENoG) is more reliable either than NET or the maximal stimulation test. However, when a facial nerve is stimulated peripheral to the injury site, the prognosis cannot be estimated correctly until the degenerations are completed in the stimulus site. Thus, NET and ENoG are not significant within 7-10 days after the onset for prognostic diagnosis.Using transcranial magnetic stimulation (TMS), the facial nerve can be stimulated around the fundus of the internal auditory meatus, which is central to the injury site in most facial palsies. Patients having a good prognosis can be identified using TMS in the early stage of palsy. Though the examination technique developed by Saito et al. (1992) is a bit complicated, antidromic facial nerve-evoked potential provides accurate information about nerve degeneration in the early stage of palsy.For bilateral facial palsy, the measurement of facial nerve conduction velocity is useful for the prognostic diagnosis (Tojima, 1988). The measurement of the distribution of facial nerve conduction velocity using Hopf's collision method (Saito, 1991) contributed to the analysis of the pathophysiology of Bell's pal-sy, which is thought to be a compression neuropathy.Blink reflex is useful in the prognostic diagnosis and also in the estimation of synkinesis as a sequela of palsy. F-waves caused by neuronal recurrent discharge due to antidromic impulse have recently been used in the estimation of recovery of damaged nerves.

Role of wavelength adaptation in the initiation, maintenance, and pharmacologic suppression of reentry.

The stability of reentry is thought to depend on a critical balance between the spatial extent of refractory tissue in a reentrant wave (i.e., wavelength lambda) and the reentrant path length. Because considerable evidence suggests that lambda changes continuously in space and time during abrupt rate changes associated with the onset of tachycardia, we hypothesized that beat-by-beat adaptation of A to the dimensions of the reentrant path plays a central role in the mechanism of initiation of reentry. To investigate the dynamic relationship between lambda and path length during initiation of reentry, optical mapping with voltage-sensitive dyes was used in a guinea pig model of reentrant ventricular tachycardia (VT). In this model, a computer-guided laser obstacle precisely controlled the position and dimensions of the reentrant path. Under control perfusion and after addition of 15 microM d-sotalol, lambda was monitored during steady-state pacing, premature stimulation, and the initiating beats leading to nonsustained and sustained VT. During control perfusion, reentrant VT was reproducibly induced in 8 of 8 hearts, whereas in the presence of d-sotalol, reentry could only be initiated in 1 of 8 hearts due primarily to the failure of lambda to adapt to the reentrant path length. During successful initiation of VT, a consistent sequence was observed. The sequence was characterized by antidromic and orthodromic propagation around both sides of the anatomic obstacle, followed by unidirectional block of the antidromic impulse and persistence of reentry only if the A of the orthodromic impulse adapted to the reentrant path (lambda < path length). d-Sotalol prevented initiation of VT by altering lambda adaptation of the orthodromic wave; however, it failed to terminate ongoing VT because reverse use-dependence developed after several beats of tachycardia. In an experimental model where lambda, path length, and cellular action potentials were monitored during initiation of reentry, we found that, in contrast to termination, the initiation of reentry and the transition from nonsustained to sustained VT is strongly dependent on beat-to-beat adaptation of lambda to the dimensions of the reentrant path.

Mechanism for site-dependent differences in the shape of the resetting response curve in fixed barrier reentry.

We investigated whether the site of stimulation within a reentrant circuit affects the resetting response curve (RRC). RRCs are used to characterize the excitable gap of reentrant circuits, including the duration of the fully excitable gap and the presence of partially excitable tissue. We reset proximal and distal to a site of interval-dependent conduction (IDC) in canine in vitro atrial tricuspid rings. Adjustable reentry allowed changes in the cycle length and direction of reentry. In nine preparations we reset 26 tachycardias. In the 16 tachycardias with one site of IDC, RRCs were significantly different when stimulating distal and proximal to a site of interval-dependent conduction. For the distal curves, the duration of the flat portion was 42 +/- 26 msec greater (P < 0.001), the slope of the increasing portion was 0.20 +/- 0.17 less (P < 0.02), and the increase in the return cycle was 14 +/- 9 msec less (P < 0.001). These differences resulted from early activation of the site of IDC by the antidromic premature impulse when stimulating from distal sites. As a result, the coupling interval of the orthodromic impulse at the site of IDC was the same or greater than at the stimulation site. In 10 tachycardias with multiple sites of IDC, significant differences in the resetting responses did not occur even when the antidromic impulse penetrated one site of IDC. In a fixed anatomic barrier reentrant circuit with one site of IDC, resetting distal to this site misrepresents the properties of the excitable gap of the entire circuit.

Evidence for functional compartmentalization of trigeminal muscle spindle afferents during fictive mastication in the rabbit.

Primary afferent neurons innervating muscle spindles in jaw-closing muscles have cell bodies in the trigeminal mesencephalic nucleus (NVmes) that are electrically coupled and receive synapses. Each stem axon gives rise to a peripheral branch and a descending central branch. It was previously shown that some spikes generated by constant muscle stretch fail to enter the soma during fictive mastication. The present study examines whether the central axon is similarly controlled. These axons were functionally identified in anaesthetized and paralysed rabbits, and tonic afferent firing was elicited by muscle stretch. For the purpose of comparison, responses were recorded extracellularly both from the somatic region and from the central axon in the lateral brainstem. Two types of fictive masticatory movement patterns were induced by repetitive stimulation of the masticatory cortex and monitored from the trigeminal motor nucleus. Field potentials generated by spike-triggered averaging of action potentials from the spindle afferents were employed to determine their postsynaptic effects on jaw-closing motoneurons. Tonic firing of 32% NVmes units was inhibited during the jaw-opening phase, but spike frequency during closing was almost equal to the control rate during both types of fictive mastication. A similar inhibition occurred during opening in 83% of the units recorded along the central branch. However, firing frequency in these was significantly increased during closing in 94%, probably because of the addition of antidromic action potentials generated by presynaptic depolarization of terminals of the central branch. These additional spikes do not reach the soma, but do appear to excite motoneurons. The data also show that the duration and/or frequency of firing during the bursts varied from one pattern of fictive mastication to another. We conclude that the central axons of trigeminal muscle spindle afferents are functionally decoupled from their stem axons during the jaw-closing phase of mastication. During this phase, it appears that antidromic impulses in the central axons provide one of the inputs from the masticatory central pattern generator (CPG) to trigeminal motoneurons.

EFFECTS OF GABA A RECEPTOR ANTAGONISM WITH BICUCULLINE ON SMOKE INHALATION IN SHEEP

S149 INTRODUCTION: Sensory nerves in the lower airways and lungs contain neuropeptides including substance P and neurokinin A, which released by a variety of irritant stimuli. This neuroinflammatory mechanism has been reported to contribute to the acute lung injury of smoke inhalation. [1] Sluka and colleagues have described a model of neuroinflammation in which a central neural reflex arc involving GABA A receptors and initiated by an injury in peripheral tissues produces antidromic impulses that feedback to sustain and amplify the initial injury by releasing neuropeptides from sensory nerves. [2] Intraspinal administration of the BABA A receptor antagonist, cicuculline reduced swelling and behavioral indicators of pain in an experimental model of peripheral inflammation. We examined the effect of bicuculline on the response to smoke inhalation in sheep. METHODS: Adult female sheep were prepared surgically for chronic study by placement of vascular catheters for hemodynamic monitoring and microsphere injection, placement of an inflatable cuff around the left pulmonary artery, and formation of a chronic lung lymph fistula. After 5 to 7 days for recovery from surgery the sheep were anesthetized with ketamine and a tracheostomy performed. Under deep halothane Anesthesia smoke inhalation injury was produced by insufflation of the lungs with cool smoke from burning cotton towels. Control animals received saline infusion while the treatment group received bicuculline 100 mg/24 hours beginning 30 minutes prior to smoke inhalation. These sheep received standard supportive treatment with mechanical ventilation and pulmonary toilet while data were collected. After 24 hours the animals were sacrificed and tissue samples obtained for analysis. RESULTS: Pulmonary gas exchange was impaired by smoke inhalation as indicated by decreases in the ration of PaO2 to FiO2 (P/F ratio). Sheep treated with bicuculline and high P/F ratios after 24 hours than the control animals (446 +/- 48 vs 309 +/- 47). Lymph flow increased in sheep with smoke insufflation. This was also reduced in sheep given bicuculline (13 +/- 4 ml/hr vs 29 +/- ml/hr at 24 hours). The wet to dry ration determined for a lung sample from a bicuculline animal was 2.36 compared to 3.5 in control animals. CONCLUSIONS: These data are consistent with central nervous system modulation of neuroinflammatory mechanisms during smoke inhalation injury in sheep.

Neocortical efferent neurons with very slowly conducting axons: strategies for reliable antidromic identification

Although simple in concept, reliable antidromic identification of efferent populations poses numerous technical challenges and is subject to a host of sampling biases, most of which select against the detection of the neurons with slowly conducting axons. This problem is particularly acute in studies of the neocortex. Many neocortical efferent systems have large sub-populations with very slowly conducting, nonmyelinated axons and these elements have been relatively neglected in antidromic studies of neocortical neurons. The present review attempts to redress this problem by analyzing the steps that must necessarily precede antidromic identification and the sampling biases associated with each of these steps. These steps include (1) initial recognition that the microelectrode is near a neuron; (2) activation of the efferent axon via the stimulating electrode; (3) conduction of the antidromic impulse from stimulation site to soma; (4) detection of the antidromic spike in the extracellular record and (5) discriminating antidromic from synaptic activation. Experimental strategies are suggested for minimizing the sampling biases associated with each of these steps; most of which can be reduced or eliminated by appropriate experimental procedures. Careful attention to such procedures will make it possible to better understand the nature and function of the information flow along the very slowly conducting axonal systems of the neocortex.

Neurogenic inf ammation in an animal model of neuropathic pain

Loose ligation of a rat sciatic nerve (chronic constriction injury (CCI) model) provokes signs and symptoms like those observed in reflex sympathetic dystrophy (RSO) patients. Primary afferent nociceptive C-fibers seem to be involved in an afferent orthodromic as well as in an efferent antidromic manner. In this study we hypothesize that consequent to development of antidromic impulses in C-nociceptive afferents, neuropeptides released from peripheral endings of these fibers, increase skin blood flow (SBF), vascular permeability, and tissue accumulation of polymorphonuclear leukocytes (PMNs). Collectively, these phenomena have been referred to as neurogenic inflammation. To investigate the presence of neurogenic inflammation in the Cel-model, we assessed skin blood flow (SBF) as well as the level of edema and accumulation ofPMNs in muscle tissue obtained from the affected hindpaw. SBF was measured, by means of laser Doppler flowmetry, before ligation as well as at day 4 after ligation. At day 4, SBF measurements were performed before and after abolition of the capability of C-fibers to mediate a vasodilator response. To this end, capsaicin was applied perineurally. Increased vascular permeability was inferred from the level of edema of muscle tissue as determined by assessment of wet,dry weight ratios of muscle biopsies. PMN accumulation was investigated by enzymatic detection of myeloperoxidase (MPO) activity in muscle biopsies. Compared with preligation values, at day 4 SBF was increased more than twofold (p < 0.05). The latter response was annihilated by capsaicin application. Compared with sham operated controls, wet,dry ratios were higher in the ligated animals (1.104 vs. 1.068; P < 0.05). Likewise, when compared with sham operated controls, MPO activity was found to be increased in the ligated hindpaw (Optic Density o. 15 vs. 0.89; P < 0.001). In conclusion, the findings of this study indicate that loose ligation of a sciatic nerve induces an inflammatory response in the ipsilateral hindpaw, which most likely is mediated by release of neuropeptides from the peripheral endings of antidromically acting nociceptive C-fibres. [Neural Res 1998; 20: 41–45]

Membrane and synaptic properties of mitral cells in slices of rat olfactory bulb

We have investigated the membrane properties and excitatory synaptic transmission of mitral cells in a slice preparation of rat olfactory bulb. In response to intracellular injection of depolarizing current, most mitral cells showed several distinct membrane properties: (1) delayed onset of firing (suggesting the presence of a type of potassium A current); (2) subthreshold oscillation of the membrane potential; and (3) repetitive firing of clustered action potentials during prolonged threshold stimulation. Olfactory nerve (ON) stimulation evoked a long-lasting EPSP in most of the mitral cells. This long EPSP was completely blocked by combined application of NMDA and non-NMDA receptor antagonists (20 μM CNQX and 100 μM APV), confirming that glutamate is the neurotransmitter at the synapses from ON to mitral cells. The ON-evoked EPSP was often preceded by a prespike, which was resistant to membrane potential hyperpolarization at the soma. This fast prepotential may be indicative of an active response in the primary dendritic tufts of the mitral cells. Stimulation of the lateral olfactory tract evoked an antidromic impulse followed by a short EPSP, which could also be elicited independently of an antidromic spike in the recorded cell. Since the asymmetrical synapses so far observed on the mitral cells are all from the ON, this antidromically evoked EPSP may reflect self-excitation of a mitral cell by glutamate released from its own dendrites by antidromic impulse invasion, or/and lateral excitation by neighboring invaded dendrites.

Reduction in amplitude of the ventral root elicited small spike by dorsal root stimulation in cat motoneurons.

Ventral root stimulation is known to produce two spikes, large and small, in the alpha-motoneuron. Since it is the small spike that triggers the outgoing impulse from the cell it is regarded as the key potential in information processing of the cell and referred to either as the IS-spike or as the A-spike depending upon whether one considers it as a purely single spike or as a composite spike. The small spike was elicited by stimulating the L 7 or S 1 ventral root in cats anesthetized with pentobarbital sodium and immobilized with d-tubocurarine. During the later phase of the excitatory prostsynaptic potential and thereto following inhibitory postsynaptic potential (IPSP) produced by stimulating the corresponding dorsal root the amplitude of the small spike was reduced by about 20%. This could be either explained as due to reduction in impedance of the membrane generating the small spike or interpreted as suggesting that the small spike is a composite spike and some of its components were inhibited by the IPSP. This interpretation was favored because the reduction occurred not when the safety factor for antidromic impulse transmission was high, but when it was low.

Reversal of reentry and acceleration due to double-wave reentry: Two mechanisms for failure to terminate tachycardias by rapid pacing

Objectives. We sought to demonstrate mechanisms by which rapid pacing can cause conduction block without terminating reentry.Background. Rapid pacing can fail to terminate or can accelerate tachycardias in patients. Mechanisms for these responses are poorly understood.Methods. We studied reentry in the canine atrial tricuspid ring and a left ventricular ring in vitro in 12 preparations. Activations were recorded from 10 sites around the ring, and monophasic action potentials were recorded from critical sites of block. Rapid pacing at cycle lengths that intermittently caused conduction block was performed at multiple sites.Results. Action potential alternans contributed to block of an orthodromic impulse during rapid pacing. When pacing continued for two stimuli after orthodromic block, a second episode of block could reverse the direction of tachycardia. Continued pacing at this site was likely to produce block of an antidromic impulse, which may initiate double-wave reentry. Double-wave reentry could be sustained or nonsustained. Its cycle length was 56% to 77% of the single-wave cycle length. The ratio of double-wave cycle length to single-wave cycle length was inversely correlated with the relative excitable gap (p < 0.01). Double-wave reentry can be a mechanism for persistent cycle length alteration during tachycardia.Conclusions. Successful termination of reentry by rapid pacing required block of an orthodromic impulse and stopping pacing within one stimulus after orthodromic block. Reversal of reentry makes the circuit resistant to termination from this site of pacing. Antidromic block can cause acceleration due to double-wave ree

Spinal tracts producing slow components of spinal cord potentials evoked by descending volleys in man

Slow negative (N) and slow positive (P) waves are frequently produced in the posterior epidural space at the lumbosacral enlargement by epidural stimulation of the rostral part of human spinal cord. The production of these slow potentials are thought to be responsible for analgesia at the stimulated segment as well as below that level. In order to define the spinal tract which mediates these slow potentials, we stimulated directly or from the epidural space the dorsal, dorsolateral, lateral and ventral columns at the cervical or thoracic level, and epidurally recorded spinal cord potentials (des.SCPs) at the lumbosacral enlargement in 7 patients who underwent spine or spinal cord surgery. The des.SCPs recorded in the lumbosacral enlargement consisted of polyphasic spike potentials followed by slow N and P waves. At a near threshold level of stimulus intensity the slow N and P potentials were consistently elicited only by stimulation of the dorsal column. The slow waves were also produced by intense stimulation of other tracts, but remained significantly ( P < 0.05− P <0.01) smaller than those evoked by dorsal column stimulation when compared at the same stimulus intensity. Moreover, the slow P wave could not be elicited even by intense stimulation (10 times the threshold strength for the initial spike potentials) of the ventral column. Thus, the results suggest that the slow N and P waves are mostly mediated by the antidromic impulses descending through the dorsal column.

The development of peripheral inflammation: Is a centrally generated, neural mechanism involved?

In the accompanying Focus article, it has been pro­ posed that the tissue changes that take place during the initiation and establishment of an acute inflam­ mation are not only mediated by peripheral mecha­ nisms, for which there is already considerable evidence, but also by a centrally driven, neuronal mechanism, the basis of which is the circuitry responsible for generating primary afferent depolarization. The suggestion is that the barrage of afferent fiber activity set up by peripheral trauma causes a general elevation of excitability of the neuronal pools with which those afferents make synap­ tic connections. Not only does this cause relay/projec­ tion neurones to become sensitized-as is now well accepted-but so too does the segmental circuitry that produces primary afferent depolarization. The excitabil­ ity change in these circuits is enough to depolarize the central terminals of afferents to such an extent that impulses are generated and these are then conducted antidromically toward the periphery; l.e., dorsal root reflexes are produced. The antidromic impulse activity in small diameter afferents, in Ao and C-fibers, results in peripheral release of pro-inflammatory neuropeptides, which contribute further to the peripheral inflammation, and in doing so close a positive feedback loop. Primary afferent depolarization underlies presynaptic inhibition, and there is no question that this form of inhi­ bition is an important mechanism in the processing of sensory information on its arrival in the central nervous system. For example, it is thought to be a way in which surround/lateral inhibition, a process that improves the discrimination capacity of the nervous system, is brought about. Dorsal root reflexes, however, could be viewed as experimental phenomena. They can be demonstrated in

Asynchrony of mossy fibre inputs and excitatory postsynaptic currents in rat hippocampus.

1. Excitatory postsynaptic currents (EPSCs) were studied by whole-cell voltage-clamp recording (WCR) from pyramidal cells in the CA3 field of rat hippocampal slices. Input from mossy fibres was evoked by stimuli applied to stratum granulosum ('dentate gyrus stimulation'). This often resulted in complex, multi-component EPSCs with rise times as long as 5.0 ms (mean = 2.5 ms). In contrast, individual EPSC components typically had rise times between 0.3 and 1.0 ms. 2. To isolate monosynaptic, mossy fibre-driven EPSC components, slices were exposed to 'suppressing' media that reduced response amplitudes by 64-88%. In five out of six cases, long EPSC rising phases (> 3 ms) retained the same shape during suppression. This implied that EPSCs were driven by asynchronously active mossy fibre inputs. 3. From latencies of antidromically driven granule cell population spikes (GCPSs) a mean conduction velocity of 0.67 m/s was inferred. Conduction distance had practically no correlation with GCPS duration, implying that velocity dispersion was small and did not desynchronize mossy fibre impulses. EPSC components exhibited 'surplus' latency; they occurred 0.9-4.8 ms after latencies expected on the basis of direct conduction distances. 4. Mossy fibre volleys (MFVs) were evoked by dentate gyrus stimulation and studied with neurotransmission disabled. MFV negative phases lasted from 2.5 to 4.5 ms and had multiple components. By comparison, negative phases of Schaffer collateral fibre volleys (SCFVs) were always simple in shape and lasted 1.5 ms or less. MFV components had surplus latencies similar to those of EPSC components. Late MFV components did not require high stimulus intensities. 5. Widespread activation of granule cells occurred when stimuli were applied to single loci in the stratum granulosum. This implies that such stimuli elicit antidromic impulses in hilar collaterals of mossy fibres, which could result in activation of orthodromic impulses in mossy fibre trunks that had not been stimulated directly. After anti-, then orthodromic conduction, impulses would arrive in the CA3 subfield with 'surplus' latency. 6. When cuts were made in the hilus to prevent anti-/orthodromic conduction, MFV durations were reduced, but only to a small extent. This implies that surplus latency and asynchrony arise in part by anti-/orthodromic conduction, and partly by a mechanism that is intrinsic to mossy fibres or their 'giant' boutons. 7. Because of desynchronization of mossy fibre inputs, there probably are significant differences between kinetic properties of averaged, compound mossy fibre EPSCs and those of unitary mossy fibre EPSCs (i.e. currents driven by input from single presynaptic axons).(ABSTRACT TRUNCATED AT 400 WORDS)