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Electrophysiological evidence of adult human skeletal muscle fibres with multiple endplates and polyneuronal innervation.

Electromyographic (EMG) signals were recorded using intramuscular electrodes at six different sites in the brachioradialis muscles during voluntary isometric contractions in four subjects. The potential waveforms and discharge patterns of up to 12 simultaneously active motor units were identified from each signal using computer-aided decomposition. Out of a total of 301 motor unit potentials identified, 23 potentials exhibited behaviour consistent with having been generated by muscle fibres that were innervated by two different motoneurons at widely separated endplates. These potentials discharged in association with two different motor units, but were blocked or delayed whenever the two motor units discharged within a few milliseconds of one another. The blocking was consistent with a collision or refractoriness when one motoneuron tried to excite the fibre while it was already conducting an action potential initiated by the other motoneuron. The delays were consistent with decreased conduction velocity associated with incomplete recovery of the fibre after a preceding action potential. From the temporal separation between the discharges of the two motoneurons that resulted in blocking, the spatial separation between the endplates was estimated to be between 26 and 44 mm. These findings challenge the classical concept of the motor unit as an anatomically distinct and functionally independent entity. It is suggested that the human brachioradialis muscle may contain both long, polyneuronally innervated fibres and short, serially linked, singly innervated fibres.

Action Potentials↗

The initiation and spread of epileptiform bursts in the in vitro hippocampal slice.

We recorded spontaneous synchronized epileptiform bursts from hippocampal slices from guinea pig using an array of 16 extracellular electrodes placed over the stratum pyramidale of CA2 and CA3. The slices were made epileptogenic with the GABA antagonist picrotoxin (or occasionally penicillin). We found that spontaneous bursts always originate at a discrete focus at or near CA2. These bursts spread smoothly and uniformly across CA3 at an average velocity of 0.13 m/s. This velocity is slower than the conduction velocity of the Schaffer collaterals or mossy fibers. Picrotoxin produced afterdischarges following the initial primary burst, and these afterdischarges were found to originate and spread in a fashion nearly identical to the primary burst. These results indicate that CA2 is a unique region which must possess unusual cellular and/or synaptic connectivity properties which result in a decreased threshold for initiation of epileptiform activity. We consider several hypothetical patterns of local synaptic connectivity in the light of these results, and we discuss the possible role of residual inhibition in limiting the spread of synchronized discharges.

Animals↗

Central compensation of vestibular deficits. II. Influences of roll tilt on different-size lateral vestibular neurons after ipsilateral labyrinth deafferentation.

The activity of 168 Deiters' neurons projecting to lumbosacral segments of the spinal cord has been recorded in precollicular decerebrate cats after ipsilateral acute (aVN) or chronic vestibular neurectomy (cVN), and their response characteristics to sinusoidal stimulation of contralateral labyrinth receptors at the standard parameters (roll tilt at 0.026 Hz, 10 degrees peak displacement) have been related to cell size inferred from the conduction velocity of the corresponding axons. These findings were compared with those elicited in decerebrate cats with both vestibular nerves intact. In all experimental conditions, the higher the coefficient of variation (CV) of the vestibulospinal neurons, reflecting a more irregular unit discharge, the lower was the mean discharge rate at rest. However, the proportion of regularly discharging units (with the lowest CV) decreased after aVN but increased after cVN. The relation found in control experiments, i.e., the faster the conduction velocity of vestibulospinal axon the lower was the unit discharge at rest, was lost after aVN due to a decrease in resting discharge rate of the slow neurons. The mean discharge rate of these units, however, recovered after cVN, so that the negative correlation between resting discharge rate and axonal conduction velocity was reestablished. After aVN, the decrease in resting discharge rate of the slow vestibulospinal neurons was not associated with significant changes in gain (impulses per second per degree) of the unit responses to standard parameters of tilt, so that the sensitivity of these units (percentage change of the mean discharge rate per degree) increased; on the other hand, the resting discharge rate of the fast neurons, which remained almost unchanged after aVN, was associated with a significant increase in gain, thus leading to an average increase in response sensitivity of these units.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Somatosensory evoked potential in man: far field potentials.

Three short latency positive potentials evoked by median nerve stimulation were recorded from the scalp, nose and ear of 11 normal adult subjects in leads where the hand or knee contralateral to the side of stimulation was used as the reference site. The short latencies and positive polarity of these components suggest that they are volume conducted far field potentials. Evidence is presented which suggests that the first potential arises in peripheral nerve fibers. Brain stem and dicencephalic structures are suggested as possible sources for the second and third potentials. The configuration of the response to median nerve stimulation recorded over the cervical spine in ear and hand reference recordings was different. Evidence is presented which suggests that this occurs because the electrode placed on the ear records the far field potentials described in the above paragraph. A far field potential was also recorded in hand--knee leads contralateral to the stimulated median nerve.

Adolescent↗

Thalamic projections from the whisker-sensitive regions of the spinal trigeminal complex in the rat.

This study investigated the axonal projections of whisker-sensitive cells of the spinal trigeminal subnuclei (SP5) in rat oral, interpolar, and caudal divisions (SP5o, SP5i, and SP5c, respectively). The labeling of small groups of trigeminothalamic axons with biotinylated dextran amine disclosed the following classes of axons. 1) Few SP5o cells project to the thalamus: They innervate the caudal part of the posterior group (Po) and the region intercalated between the anterior pretectal and the medial geniculate nuclei. These fibers also branch profusely in the tectum. 2) Two types of ascending fibers arise from SP5i: Type I fibers are thick and distribute to the Po and to other regions of the midbrain, i.e., the prerubral field, the deep layers of the superior colliculus, the anterior pretectal nucleus, and the ventral part of the zona incerta. Type II fibers are thin; branch sparsely in the tectum; and form small-sized, bushy arbors in the ventral posterior medial nucleus (VPM). Accordingly, a statistical analysis of the distribution of antidromic invasion latencies of 96 SP5i cells to thalamic stimulation disclosed two populations of neurons: fast-conducting cells, which invaded at a mean latency of 1.23 +/- 0. 62 msec, and slow-conducting cells, which invaded at a mean latency of 2.97 +/- 0.62 msec. 3) The rostral part of SP5c contains cells with thalamic projections similar to that of type II SP5i neurons, whereas the caudal part did not label thalamic fibers in this study. A comparison of SP5i projections and PR5 projections in the VPM revealed that the former are restricted to ventral-lateral tier of the nucleus, whereas the latter terminate principally in the upper two tiers of the VPM. These results suggest a functional compartmentation of thalamic barreloids that is defined by the topographic distribution of PR5 and type II SP5i afferents.

Animals↗

Synthesis of generalized algorithms for the fast computation of synaptic conductances with Markov kinetic models in large network simulations.

Markovkinetic models constitute a powerful framework to analyze patch-clamp data from single-channel recordings and model the dynamics of ion conductances and synaptic transmission between neurons. In particular, the accurate simulation of a large number of synaptic inputs in wide-scale network models may result in a computationally highly demanding process. We present a generalized consolidating algorithm to simulate efficiently a large number of synaptic inputs of the same kind (excitatory or inhibitory), converging on an isopotential compartment, independently modeling each synaptic current by a generic n-state Markov model characterized by piece-wise constant transition probabilities. We extend our findings to a class of simplified phenomenological descriptions of synaptic transmission that incorporate higher-order dynamics, such as short-term facilitation, depression, and synaptic plasticity.

Algorithms↗

[Identification and study of sympathoactivating neurons of the medulla oblongata].

The neurons with descending axons which activate the lateral horn sympathetic preganglionic (vasomotor) neurons were searched in the lower brain stem of the cat. Localization of these sympathoactivatory neurons in the limit zone of medulla was outlined by means of scanning stimulation. The identification of single bulbar sympathoactivatory neurons was based on the recording of their antidromic discharges elicited by stimulation of descending sympathoactivatory pathways with conduction velocity about 4--8.9 m/s in the dorsolateral funiculi of the cervical spinal cord. The neurons studied have a very low frequency spontaneous discharges (0.1--1.0 imp/s) unrelated with cardiac and respiratory cycles. The alterations of spontaneous discharge frequency were in strict correlation with pressor phases of Maer waves and pressor reflex reactions. The inhibitory effects of the baroreceptor nerve stimulation on spontaneous and elicited discharges of these neurons were never seen. A possible role of the sympathoactivatory neurons identified as an output elements of the bulbar "vasomotor" centre is discussed.

Animals↗

Nerve regeneration across an extended gap: a neurobiological view of nerve repair and the possible involvement of neuronotrophic factors.

We have compared the anatomic and functional regeneration of a transected sciatic nerve following regrowth from its proximal stump through either preformed empty mesothelial chambers or autologous nerve grafts bridging a 10 mm gap. Within the mesothelial chambers an organized multifascicular nerve trunk forms between the proximal and distal stumps. After 3 months, distal segment cross sections from the mesothelial chamber and nerve graft groups did not differ with respect to axonal density or distribution of axonal diameters. Mean conduction velocities across the gaps were also similar, although the nerve graft group had a wider distribution of velocities. Little or no regeneration was evident when the gap between the nerve stumps was left empty. These results suggest that if the regrowing proximal stump is in an appropriate environment, it can form a well organized and oriented nerve trunk. In the mesothelial chambers, the regenerating nerve is surrounded by a loose cellular stroma and a small amount of interstitial fluid, which was found to contain trophic activity for cultured rodent sensory neurons. Such factors may also support nerve regeneration in vivo.

Animals↗

Phrenic motoneurons in the cat: subpopulations and nature of respiratory drive potentials.

1. Intracellular recordings were made from 78 phrenic motoneurons (PM) in anesthetized, paralyzed, artificially ventilated cats that were slightly hypercapnic. 2. Three subpopulations of PM (types A, B, and A/B) were identified on the basis of their membrane potential trajectories during expiration (E). Type A cells exhibited wholly linear trajectories. These were rapidly hyperpolarized at the onset of E followed by a slow ramp of increasing hyperpolarization observed in 51 of 59 type A cells. Types B (13 cells) and A/B (6 cells) had nonlinear trajectories in E. Type B cells approached their end-expiratory potential levels more slowly. 3. Measurements of axonal conduction velocity, expiratory phase input resistance, initial depolarization rate, and initial spike onset during inspiration revealed that type B cells had significantly slower axonal conduction velocities, higher input resistances, greater initial depolarization rates, and earlier initial spike onsets than type A cells. The properties of type A/B were intermediate between the other cell types. These results support the hypothesis that the PM pool is not homogeneous. 4. Active E-phase inhibition of all types of PM was directly demonstrated by reversal of the increasing hyperpolarizing wave to a depolarizing wave with hyperpolarizing current injection using a bridge circuit. Thus hyperpolarization of PM during E is not merely due to a central disfacilitation. 5. During hyperpolarizing current injection the inspiratory phase membrane potential trajectory of all PM became a ramp depolarization similar to that seen during control conditions in type A cells. These results support the conclusion that all cells within the PM pool are receiving a similar central excitatory synaptic input during inspiration. The rapid initial depolarization of type B and their concomitant early spike onset is a consequence in part of a rebound excitation from their expiratory phase inhibition as well as a higher input resistance, probably due to a smaller cell size. 6. Expiratory related neural activity was recorded within the phrenic motor nucleus. It is suggested that these expiratory related neural elements, based on the temporal pattern of their activity, may be responsible for the active inhibition of PM.

Animals↗

Phenotypic identification of rat rostroventrolateral medullary presympathetic vasomotor neurons inhibited by exogenous cholecystokinin.

Systemic administration of the gastrointestinal hormone cholecystokinin (CCK) selectively inhibits splanchnic sympathetic vasomotor discharge and differentially affects presympathetic vasomotor neurons of the rostroventrolateral medulla (RVLM). Stimulation of the sympathoexcitatory region of the periaqueductal grey (PAG) produces profound mesenteric vasoconstriction. In this study, our aim was to identify phenotypically different populations of RVLM presympathetic vasomotor neurons using juxtacellular neuronal labelling and immunohistochemical detection of the adrenergic neuronal marker phenylethanolamine-N-methyl transferase (PNMT) and to determine whether the PAG provides functional excitatory input to these neurons. Fifty-eight percent (36/62) of RVLM presympathetic neurons were inhibited by systemic administration of CCK. These cells had conduction velocities (3.6 +/- 0.2 m/sec) in the non-C-fiber range consistent with neurons possessing lightly myelinated spinal axons. Of these, 79% (22/28) were excited by PAG stimulation, and 59% (10/17) were not immunoreactive for PNMT. Conversely, 42% (26/62) of RVLM presympathetic neurons were either unaffected or activated by CCK administration and had slower conduction velocities (1.4 +/- 0.3 m/sec) than cells inhibited by CCK. Fifty percent (11/22) of these cells were driven by PAG stimulation, and most (11/14 or 79%) were PNMT-positive. These results suggest that cardiovascular responses elicited by PAG stimulation occur via activation of non-C1 and C1 RVLM presympathetic neurons. RVLM neurons inhibited by CCK were more likely to be driven by PAG stimulation and may be a subset of neurons responsible for driving gastrointestinal sympathetic vasomotor tone. CCK-induced inhibition of a subpopulation of RVLM presympathetic neurons may be implicated in postprandial hyperemia and postprandial hypotension.

Animals↗

Electrophysiological studies and physical examinations in entrapment neuropathy: sensory and motor functions compensation for the central nervous system in cases with peripheral nerve damage.

We performed electrophysiological studies and objective physical examinations in 60 patients with carpal tunnel syndrome and 21 patients with cubital tunnel syndrome. Compared with our normal data, the sensory nerve conduction velocity across the wrist was defined as abnormal in 97% of the carpal tunnel syndrome patients, the corresponding value of the amplitude of the sensory nerve action potential was 58% and the value of the two point discrimination test was 28% while the value of the Semmes-Weinstein monofilament test was defined as abnormal in 64% of the cases. In cubital tunnel syndrome patients, motor nerve conduction velocity across the elbow was defined as abnormal in 91%, the amplitude of the M-wave was 96%, manual muscle testing was 63% and their side pinch strength was defined as abnormal in 24% of the cases. The functions of recognition are preserved in the cases with moderate damage of peripheral nerve due to the cancellation of synaptic occlusion. Motor performance also compensated in the central nervous system. Therefore the sensitivity of the objective physical examination is less than that of electrophysiological study of peripheral nerve itself. For entrapment neuropathy electrophysiological findings are more sensitive than the objective physical examinations.

Adolescent↗

New method for the objective evaluation of injury to the lingual nerve after operation on third molars.

Existing tests of function of the lingual nerve are either subjective or, when they elicit the jaw-opening reflex, are dependent on the cooperation of the subject. We report a study in 12 healthy volunteers and 12 patients with iatrogenic injury to the lingual nerve. A bite block (containing stimulating electrodes) was held between the teeth and the tongue was held on to the electrodes by suction. When the lingual nerve was intact, an electrical stimulus elicited brief inhibition of masseteric electromyographic activity. Local analgesia and iatrogenic injury to the lingual nerve altered nerve conduction and caused a reduction in reflex inhibition. Two methods, compatible with limited numbers of applications of the stimulus, were used to quantify responses. One used an indirect measurement of intervals between action potentials of muscle and the other used a measurement of rectified signals falling below the mean amplitude before and after the stimulus. Both methods gave values that correlated with subjective sensations. The first gave an estimate of the probability of defining major malfunction of the nerve objectively; the second gave a linear measurement that allowed recovery of the nerve to be followed.

Action Potentials↗

An intracellular analysis of geniculo-cortical connectivity in area 17 of the cat.

The latencies of excitatory and inhibitory post-synaptic potentials (e.p.s.p.s and i.p.s.p.s) evoked by electrical stimulation of afferents from the lateral geniculate nucleus were recorded in neurones of area 17 of the cat visual cortex. After application of an extrapolation procedure to compensate for the conduction time of the afferent axons, a histogram of latencies formed three distinct peaks. Potentials in each of these were interpreted as being mediated by mono-, di- and trisynaptic pathways. Characteristic laminar differences in the extracellular field potentials evoked from the lateral geniculate nucleus (l.g.n.) and in the antidromic activation of neurones from the l.g.n. and superior colliculus were used to determine the laminar position of recorded neurones. It was found that within a given layer, all cells maintained similar connexions with relay cells in the l.g.n. Cells in layers 3, 4, upper 5 and 6 were monosynaptically excited by geniculate afferents, while cells in layers 2 and lower 5 received only indirect excitation via other cortical neurones. Layer 3 cells were unique in receiving a prominent disynaptic e.p.s.p. in addition to the direct excitation from the l.g.n. Late, trisynaptic e.p.s.p. components were seen in many layer 5 and 6 cells. The orderly laminar arrangement of the connexions had the consequence that identified cortico-geniculate neurones were monosynaptically excited and cortico-collicular neurones di- and trisynaptically excited by geniculate afferents. Cortico-cortical neurones in layers 2 and 3 received di- or mono- plus disynaptic excitation, depending on laminar position. Post-synaptic inhibitory potentials were evoked in all impaled cells, following stimulation of the geniculo-cortical pathway. Except for a few layer 2 cells, this inhibition was mediated through disynaptic pathways of the feed-forward type. There was a good positive correlation between conduction times for monosynaptic e.p.s.p.s and disynaptic i.p.s.p.s in the same cells, suggesting that cortical neurones receive excitation and inhibition from the same type of geniculate afferents. The stimulating electrodes activated not only geniculo-cortical afferents, but antidromically activated cortical efferent neurones from their extracortical axons. These neurones possess intracortical collaterals, and care must be taken to distinguish the resulting potentials from those mediated by orthodromic activation of geniculate afferents. In doing so, evidence was obtained for excitatory connexions from layers 2 and 3 to layer 5, from layer 5 to layer 6, and from layer 6 to layer 4. Typical recurrent inhibition was not observed.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗

Long-latency spinal reflexes in humans.

Stretching human muscles with a mechanical device gave rise to multiple peaks in the rectified and averaged electromyogram. In the first dorsal interosseous the latency of the first peak (M1) was 32.4 +/- 2.4 ms (SD) and the latency of the second peak (M2) was 55.1 +/- 11.3 ms, in both cases measured from the time of the stimulus to the take-off point of the peak. Often a third peak (M3) was seen, having a considerably longer latency. The origin of peak M1 was considered to be in the stretch reflex arc because of its latency and its invariable association with muscle movement. Peak M2 was due to stimulation of afferent terminals in the skin and/or subcutaneous tissues by the mechanical device producing the muscle stretch. The conduction velocity of the pathway involved in the generation of the M1 component is the same as that for M2. This implies that central processing in the spinal cord delays the M2 response. The M2 mechanism does not involve a transcortical (long-loop) pathway because in foot muscles the M1-M2 delay remains the same as is found for hand muscles, although M1 latency is prolonged (to 39.4 +/- 6.2 ms for extensor digitorum longus). This indicates that there is not time for M2 impulses to traverse a pathway any longer than that passing to and from the spinal cord.

Afferent Pathways↗

Spinal and muscle motor evoked potentials following magnetic stimulation in cats.

Motor evoked potentials (MEP) from transcranial magnetic stimulation were successfully recorded from the spinal cord and gastrocnemius muscle in cats. The spinal MEP consisted of four negative peaks, N1 through N4, and subsequent small, multiphasic waves. The conduction velocity calculated from N1 corresponded to that of the nonpyramidal cerebellar evoked potential. After ablation of the pyramidal tract at various levels, N1 through N3 persisted, whereas N4 disappeared. The muscle MEP showed the same latency as that of MEP obtained by direct cortical electrical stimulation and disappeared after similar ablation. These findings suggest that the first three peaks of the spinal MEP are responses of the nonpyramidal cerebellospinal pathways and that the fourth peak of the spinal MEP and the muscle MEP are pyramidal tract responses. Spinal and muscle MEP from magnetic stimulation may be valuable in the qualitative evaluation of the function of the pyramidal and nonpyramidal pathways.

Animals↗

[Functional characteristics and topography of spinal tracts involved in low- and high-threshold startle reflexes].

Electrophysiological and topographical properties of the spinal tract systems involved in two functional types of startle reflexes were studied in chloralose anesthetized cats: a high threshold reflex evoked by intense peripheral nerve stimulation (spino-bulbo-spinal, SBS, reflex) and low threshold evoked by tactile (T-reflex) and acoustic (A-reflex) stimulation. It was found that the mean maximal conduction velocity of descending transmission of SBS-reflexes was much less (30 m/s) than that of T- (85 m/s) and A-reflexes (100 m/s). Ascending conduction velocities for SBS- and T-reflexes were 70.8 and 40.2 m/s, respectively. It was established by partial spinal cord lesions that ascending tracts for T-reflex passed in dorsal and dorso-lateral funiculi; those for SBS reflexes were found not only in the latter but also in ventro-lateral and partially in ventral funiculi. Descending pathways for SBS reflex passed mainly in ventro-lateral funiculi and partially in the ventral ones. Descending pathways of T- and A-reflexes had a similar organization and were located mainly in the ventral and ventro-lateral funiculi. Functional organization of spinal tracts of all studied types of startle reflexes is discussed.

Acoustic Stimulation↗

Alterations in the oligodendrocyte lineage, myelin, and white matter in adult mice lacking the chemokine receptor CXCR2.

Oligodendrocyte precursor cell (OPC) proliferation and migration are critical for the development of myelin in the central nervous system (CNS). Previous studies showed that localized expression of the chemokine CXCL1 signals through the receptor CXCR2 to inhibit the migration and enhance the proliferation of spinal cord OPCs during development. Here, we report structural and functional alterations in the adult CNS of Cxcr2-/- mice. In Cxcr2-/- adult mice, we observed regional alterations in the density of oligodendrocyte lineage cells in Cxcr2-/- adult mice, with decreases in the cortex and anterior commissure but increases in the corpus callosum and spinal cord. An increase in the density and arborization of spinal cord NG2 positive cells was also observed in Cxcr2-/- adult mice. Compared with wild-type (WT) littermates, Cxcr2-/- mice exhibited a significant decrease in spinal cord white matter area, reduced thickness of myelin sheaths, and a slowing in the rate of central conduction of spinally elicited evoked potentials without significant changes in axonal caliber or number. Biochemical analyses showed decreased levels of myelin basic protein (MBP), proteolipid protein (PLP), and glial fibrillary acidic protein (GFAP). In vitro studies showed reduced numbers of differentiated oligodendrocytes in Cxcr2-/- spinal cord cultures. Together, these findings indicate that the chemokine receptor CXCR2 is important for the development and maintenance of the oligodendrocyte lineage, myelination, and white matter in the vertebrate CNS.

Animals↗

Inhibitory nigral influence on cerebellar evoked responses in the rat ventromedial thalamic nucleus.

The ventral medial nucleus of the thalamus (VM) has been shown in rats and cats to constitute a common target for nigro- and cerebello-thalamic pathways. In the present study the responses of VM neurons to ipsilateral substantia nigra (SN) and contralateral cerebellar nuclei stimulation were analyzed in the rat. The typical response of VM neurons to SN stimulation consisted of a pure short-latency (1.1-3 ms), short-duration (7-17 ms) IPSP. Latencies of these responses were accorded well with the conduction velocity of the nigro-thalamic fibers as measured on the basis of antidromic activation of this pathway. A high percentage (58%) of the thalamic neurons receiving the inhibitory nigral effect were also affected by cerebellar stimulation. The cerebellar effect consisted of a short-latency depolarizing potential which could trigger an action potential. These responses were invariably blocked during the course of SN evoked inhibition. Such convergence was found with fastigial as well as interpositus/dentatus evoked responses. The demonstration of an interaction between the processing of SN and cerebellar output at thalamic level provides an important clue for the understanding of the neurophysiologic mechanisms by which SN acts on motor behavior.

Animals↗