Variability of cortical evoked responses in man related to slow wave activity

Summary Acoustically evoked responses were recorded from subdural and intracerebral electrodes chronically implanted in man. it was found that during slow wave activity especially the negative component at about 100 ms latency varies in form and amplitude. If the stimuli were presented during increasing cortical negativity, the amplitude of the 100 ms component of the evoked responses was generally larger than in the case of stimuli presented during decreasing negativity.Supported by the Fonds zur Förderung der wissenschaftlichen Forschung in Österreich, Project 1429, and the British Council.     

Down-regulation of tumor necrosis factor α activity by acute ethanol treatment in human peripheral blood monocytes

As the most commonly used drug that can modulate both metabolic and immune pathways, ethanol is evaluated in this report as a regulator of tumor necrosis factor (TNF) production in human peripheral blood monocytes (M) in combination with a variety of stimuli. While acute ethanol treatment did not induce TNF in M, it was a potent down-regulator of M TNF production whether induced by the combination of interferon- plus muramyl dipeptide (MDP) (P<0.001), lipopolysaccharide (LPS) alone (P<0.01), or interferon- plus LPS. Down-regulation of M TNF by ethanol was dose dependent and statistically significant in the biologically relevant, 25–150 mM, ethanol concentration range. We also demonstrate that these ethanol concentrations did not affect M viability. TNF down-regulation by ethanol was most effective when ethanol was administered 4 hr prior to MDP stimulation; however, it was also effective—though to a lesser extent—if it was added at the time of MDP stimulation. Furthermore, ethanol also down-regulated TNF production of thein vivo preactivated M of trauma patients, which produce hyperelevated levels of TNF. We have previously shown that the majority of posttrauma elevated M TNF is produced by the M subpopulation expressing high-affinity type I Fc receptors (FcRI). When the FcRI cross-linking-stimulated M subpopulation was treated with acute ethanol, TNF production was suppressed again both inin vivo preactivated M of trauma patients and in M of normal controls. In experiments utilizing cyclooxygenase inhibitor, we also demonstrate that ethanol has a direct, prostaglandin E₂-independent, effect on M TNF production. These results demonstrate that acute ethanol exposure has the potential to down-regulate M production of TNF significantly regardless of the TNF-inducing stimulus. Decreased capacity of M to produce TNF might, therefore, contribute to the immunological and metabolic abnormalities described after ethanol uptake.     

Convergent inputs from articular,cutaneous and muscle receptors onto ascending tract cells in the cat spinal cord

Summary 1.Responses were recorded from 160 ascending tract cells in segments L4 to L6 of the spinal cord in chloralose anaesthetized, spinalized cats. The tract cells were identified by antidromic activation following stimulation of pathways in the lateral and ventral funiculi at the level of the spinal cord transection at the thoracolumbar junction. Axonal conduction velocities ranged from 9 to 114 m/s. 2. A sample of 152 of the neurones examined could be subdivided according to the distribution of their receptive fields into 49 cells activated just from receptors located in skin (s cells), 17 neurones excited by receptors in deep tissues (d cells), 15 units with a convergent input from receptors in skin and deep tissues (sd cells), and 25 neurones with a convergent input from the knee joint and either skin (sj cells), deep tissues (dj cells) or both (sdj cells). No receptive fields could be demonstrated for the remaining 46 neurones. 3. S and sj cells were found almost exclusively in the dorsal horn, whereas many d, sd, sdj and dj units were in the ventral horn. Almost all of the cells that lacked receptive fields were in the ventral horn or intermediate grey. 4. Ninety-one of 158 cells (56%) demonstrated no background activity. Of these, 43 cells (27%) lacked receptive fields. Many of the silent neurones were in the ventral horn, but some were in the dorsal horn. Of 25 cells having knee joint input, 18 (72%) had background activity. 5. All of the neurones that had a receptive field in the knee joint also had a convergent input from receptors in other tissues. In 3 cases, there was a receptive field in the skin over the foot (sj cells). For 16 cells, receptive fields included not only the knee joint but also skin and deep tissue (sdj cells). Usually, the cutaneous receptive field was near the knee joint, but sometimes it was remote, such as on the foot. The deep receptive fields were chiefly in the muscles of the thigh and/or leg. For 6 dj cells, the receptive fields included not only the knee joint but also deep fields like those of sdj cells. 6. Cutaneous receptive fields were classified as low threshold (cells excited best by innocuous intensities of mechanical stimulation), wide dynamic range (cells activated by weak mechanical stimuli, but the best responses were to noxious stimuli) or high threshold (innocuous stimuli had little effect, but noxious mechanical stimuli produced a vigorous discharge). Similarly, stimulation of the knee joint with weak mechanical stimuli could excite some neurones, while others could be activated by weak or strong articular stimuli but were excited best by noxious stimuli, and still other neurones were activated by knee joint stimuli only if the intensity was noxious. 7. In several instances, contralateral receptive fields were noted. These were generally in deep tissue or in the knee joint. 8. It was concluded that many of the responses to articular stimulation of the spinal cord ascending tract cells examined in this study could have been mediated by the fine afferent fibres that supply the knee joint. Although further work will be required to determine which particular ascending tracts transmit nociceptive information concerning the knee joint, it can be proposed that many of the responses demonstrated here were likely to play a role in either joint pain of in triggering responses associated with joint pain.     

Predictive behavior of optokinetic eye movements

Summary Optokinetic nystagmus is often thought of as a primitive oculomotor response, while smooth pursuit is thought of as a higher one. We have used conditions that are usually thought of as eliciting optokinetic responses; i.e., large-field stimuli confined to the retinal periphery, and instructions to subjects to respond passively. In spite of this, the responses showed predictive behavior similar to that described for smooth pursuit.     

Time constants of facilitation and depression in Renshaw cell responses to random stimulation of motor axons

Summary In 9 adult anaesthetized cats, 22 lumbosacral Renshaw cells recorded with NaCl-filled micropipettes were activated by random stimulation of ventral roots or peripheral nerves. The stimulus patterns had mean rates of 9.5–13 or 20–23 or 45 pulses per second and were pseudo-Poisson; short intervals below ca. 5 ms (except in two cases) were excluded. The Renshaw cell responses were evaluated by two kinds of peristimulus-time histograms (PSTHs). Conventional PSTHs were calculated by averaging the Renshaw cell discharge with respect to all the stimuli in a train. These PSTHs showed an early excitatory response which was often followed by a longer-lasting slight reduction of the discharge probability. These two response components were positively correlated. Conditional PSTHs were determined by averaging the Renshaw cell discharge with respect to the second (test) stimulus in pairs of stimuli which were separated by varied intervals, . The direct effect of the first conditional response was subtracted from the excitation following the second (test) stimulus so as to isolate the effect caused by the second stimulus per se. After such a correction, the effect of the first conditioning stimulus showed pure depression, pure facilitation or mixed facilitation/depression. Analysis of such conditioning curves yielded two time constants of facilitation (ranges: ca. 4–35 ms and 93–102 ms) and two of depression (ranges: ca. 7–25 ms and 50–161 ms). It is concluded that these time constants are compatible with processes of short-term synaptic plasticity known from other synapses. Other processes such as afterhyperpolarization and mutual inhibition probably are of less importance.     

Intratypic antigenic heterogeneity of Coxsackie B viruses

Summary Neutralization tests, employing the cytopathogenic effect in tissue culture tubes, with a variety of homotypic antisera and strains of Coxsackie B viruses often yielded high titers in early readings and low titers in late readings — the break-through phenomenon — and occasionally also low, early-reading titers with heterologous, homotypic sera, which gave high titers with the homologous strains. Of 27 strains of Goxsackie B 1 to B 5, that were tested, 10 showed no break-through tendency while others showed varying degrees of break-through, without reference to any evidence of intratypic antigenic variation. There was a positive correlation between a small number of tissue culture passages away from man or mouse brain and the break-through tendency. Moreover, strains without break-through tendency yielded viral populations with marked break-through properties after a single intracerebral passage in newborn mice, and even after two subsequent tissue culture passages. Plaque-purified progeny exhibited the break-through phenomenon to the same extent as the original, unpurified cultures.The early readings yielded reproducible titers, which could be used for analysis of antigenic variation. Prime antigenic variants, of broader antigenic constitution than their non-prime relatives, were found among the Coxsackie B 2, B 3, and B 4 strains that were tested. These prime strains (e. g., B. V. A. 96- B2; Stevens - B 3, and Burrier or J. V. B. - B 4) were found to be antigenically broader than the prototype strains (Ohio 1 - B 2, Nancy - B 3, Powers or Texas 13 - B 4) generally used for the preparation of diagnostic antisera. The broader antigenicity of the prime variant was also present in plaque-purified progeny.Aided by grants from The National Foundation, Inc.The work reported here was carried out in 1957–1958 during Dr.Wigand's tenure of a fellowship in the Cincinnati Laboratory.     

Short latency cutaneous reflex responses of γ-efferents in the decerebrate cat

Summary The effect of single shock stimulation, up to 20 × threshold (T), of the sural nerve on the discharges of triceps surae -efferents was investigated in decerebrate cats. Units were classified as static (12) or dynamic (7) on the basis of their resting discharge rates (Murphy et al. 1984). All neurones were excited at short latency by sural nerve stimulation and response size was graded with stimulus intensity. Short latency mixed or inhibitory responses were not evident. Although reflex effects first occurred at low stimulus strengths (<-1.5T) in both types of efferent, most responses appeared at higher intensities (> 1.5T). The estimated central delays of the responses of static (3.0 ±1.1 ms, mean± SD) and dynamic (3.4 ± 1.0 ms) -motoneurones were not significantly different and are consistent with spinal oligosynaptic pathways. The present results differ from those of the only previous study (Johansson and Sojka 1985) of the short latency responses of triceps surae static and dynamic -motoneurones to sural nerve stimulation, in which mixed and inhibitory effects were common in anaesthetised cats. Although differences in recording techniques and sampling may account for the apparent disparity between these studies, it is also feasible that a difference in the setting of interneuronal pathways in the two types of preparation is responsible. The results are discussed in relation to the control of -motoneurones with particular reference to the final common input hypothesis (Johansson 1981; Appelberg et al. 1983).     

Far-field somatosensory evoked potentials in response to selective stimulation of small diameter myelinated fibers in the cat

Summary Five far-field components were identified preceding the cortical wave in response to the stimulation of the A fibers of the sural nerve. When A activity was also included in the afferent volley, a second cortical wave and additional far-field potentials were recorded. Upon blocking the A fiber activity and thus isolating the peripheral input to A fibers alone, the initial cortical wave and the far-field potentials preceding it disappeared completely, leaving the A evoked potentials intact.     

The ansa cervicalis and the infrahyoid muscles of the rat

Summary Perikarya of motoneurons and spinal ganglion cells attributed to infrahyoid muscle nerves of the rat were labelled by retrogradely transported horseradish peroxidase (HRP). For the differentiation of motor and sensory axons cross sections of the nerves were stained for acetylcholinesterase. Numbers and diameter distributions of perikarya and myelinated axons were determined.Motoneuronal perikarya innervating the infrahyoid muscles are located from the transition zone brain stem/spinal cord to the segment C 3. They are found mostly in the medial part of the Rexed laminae VII and VIII at the level of C 1 and C 2 and more ventrolaterally in C 3 and are therefore located to a large extent in areas until now not recognized to contain motoneurons. Our results provide evidence for a somatotopic organization of the motoneurons in the upper cervical spinal cord.The diameter distributions of motoneuronal perikarya and axons are in most cases bimodal, the two modes corresponding to -and -motoneurons. In relation to the diameters of their perikarya -axons are significantly thicker than -axons. In contrast to the motoneurons no clear correlation could be established between the sizes of perikarya of spinal ganglion cells and their peripheral processes.This work was partly supported by the Hartmann Müller-Stiftung Zürich     

”Reflexes of purpose and freedom” in the comparative physiology of higher nervous activity

The most complex unconditioned reflexes of aim and freedom, discovered by I. P. Pavlov, are compared with the competence drive and the motivation of the resistance to coercion, respectively, described by contemporary ethologists. On the basis of the unconditioned reflex of purpose, conditioned reflexes were developed in which positive emotions arising in connection with the perfection of a skill, irrespective of its pragmatic significance at a given moment, serve as the reinforcement. The unconditioned reflex of freedom is regarded as a phylogenetic precursor of the will, and its acute extinction as the physiological mechanism of hypnosis. It was demonstrated experimentally that the appearance of the state of animal hypnosis (immobilization catatonia) in rabbits is accompanied by the predominance of electrical activity and heat production in the right hemisphere, i. e., by symptoms which are found in hypnosis in man.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 39, No. 3, pp. 415–420, May–June, 1989.     

Some observations on responses evoked by pinna stimulation in efferent and afferent fibres innervating hind limb muscle spindles of the rat

Summary Pinna stimulation has long been known to evoke reflex changes of discharge in efferents to the hind limb and hence changes in muscle spindle discharges. The present experiments were made in the rat to determine the involvement of the static and dynamic fusimotor systems in the pinna reflex.We first observed fusimotor activity indirectly, by recording spindle responses to various length changes with and without concurrent pinna stimulation. Afferent responses were clearly influenced by static fusimotion during the reflex; evidence for dynamic fusimotion was sought but not found. Ipsilateral and contralateral stimuli appeared equally effective in evoking this static fusimotion.The magnitudes of afferent responses differed markedly between muscles. Observations were made simultaneously on activities recorded directly from efferents to peroneal and soleus muscles. Several efferents were spontaneously active in each nerve; pinna stimulation usually enhanced their activities and aroused also several others, previously quiescent. The frequencies of discharge in efferents to peroneus were usually higher than in those to soleus. This must in part be responsible for differences in afferent responses. The spontaneously active and activated fibres together formed about one quarter to one third of the total motoneurone pool and had conduction velocities restricted to the lower end of the conduction velocity spectrum for fibres.     

Afferent control of human stance and gait: evidence for blocking of group I afferents during gait

Summary The cerebral potentials (c.p.) evoked by electrical stimulation of the tibial nerve during stance and in the various phases of gait of normal subjects were compared with the c.p. and leg muscle e.m.g. responses evoked by perturbations of stance and gait. Over the whole step cycle of gait the c.p. evoked by an electrical stimulus were of smaller amplitude (3 V and 9 V, respectively) than that seen in the stance condition, and appeared with a longer latency (mean times to first positive peak: 63 and 43 ms, respectively). When the electrical stimulus was applied during stance after ischaemic blockade of group I afferents, the c.p. were similar to those evoked during gait. The c.p. evoked by perturbations were larger in amplitude than those produced by the electrical stimulus, but similar in latencies in both gait and stance (mean 26 V and 40 V; 65 ms and 42 ms, respectively) and configurations. The large gastrocnemius e.m.g. responses evoked by the stance and gait perturbations arose with a latency of 65 to 70 ms. Only in the stance condition was a smaller, shorter latency (40 ms) response seen. It is concluded that during gait the signals of group I afferents are blocked at both segmental and supraspinal levels which was tested by tibial nerve stimulation. It is suggested that the e.m.g. responses induced in the leg by gait perturbations are evoked by group II afferents and mediated via a spinal pathway. The c.p. evoked during gait most probably reflect the processing of this group II input by supraspinal motor centres for the coordination of widespread arm and trunk muscle activation, necessary to restablish body equilibrium.     

Serotonin reveals ineffective spinal pathways to contralateral phrenic motoneurons in spinally hemisected rats

Serotonin reveals ineffective (subthreshold) pathways from the C2 lateral funiculus to ipsilateral phrenic motoneurons in spinalized rats. The objective of the present study was to investigate serotonergic modulation of crossed-spinal pathways to contralateral phrenic motoneurons. Rats (n = 10) were anesthetized (urethane), paralyzed, vagotomized, and artificially ventilated. The spinal cord was hemisected at C1–C2 and, on the intact side, a tungsten stimulating electrode was placed ventral to the C2 dorsal root entry zone in the dorsolateral ( 1.1 mm) or the ventrolateral funiculus (2.2 mm depth). Single shocks (100–750 A, 0.1–0.5 ms, 2 Hz) elicited a short-latency ( 1.0 ms to peak) excitation in the ipsilateral phrenic nerve, but usually evoked little or no response in the contralateral phrenic nerve at either stimulus site. Following systemic injection of the monoamine oxidase inhibitor pargyline (25 mg/kg) and the serotonin precursor 5-hydroxytryptophan (5–10 mg/kg), complex responses were revealed in the contralateral phrenic nerve, including; (1) spontaneous tonic activity; (2) a short-latency (1.0 ms to peak) evoked excitation; and (3) two long-latency (2.2 and 7.8 ms to peak) evoked excitations. The longest latency excitation was expressed only when the stimulating electrode was positioned in the dorsolateral funiculus. Contralateral evoked responses were blocked by systemic methysergide (2–6 mg/kg), a broad-spectrum serotonin receptor antagonist. These results indicate that serotonin converts ineffective crossed phrenic pathways in the spinal cord to effective pathways. It remains to be determined whether serotonin is both necessary and sufficient in this modulatory process, or if it is a nonspecific result of increased phrenic motoneuron excitability.     

Brief Communication: cDNA Sequence and Mapping of the Mouse Copb Gene Encoding the Beta Subunit of the COPI Coatomer Complex

COPI-coated vesicles are involved in retrograde-directed selective transport of proteins from the Golgi complex to the endoplasmic reticulum (ER) as well as mediate anterograde transport of cargo proteins within the Golgi or in endosomal trafficking. The COPI protein complex contains an ADP-ribosylation factor (ARF1) and seven coatamer subunits (, , , , , , -COP). The localization and function of human subunit of coatamer (COPB) suggests it is likely a candidate gene of ruby-eye-2 (ru2), which is a mouse model of human Hermansky-Pudlak syndrome characterized by the dysfunction of several subcellular organelles. In this study, we determined the entire coding sequence of mouse (Copb) cDNA by combining an overlapping mouse EST contig with EST walking. -COP was found highly conserved in mouse, rat, and human, and it is ubiquitously expressed in mouse. The Copb gene was mapped to mouse Chr 7 at a position of 53.3 cM by radiation hybrid mapping. Our RH mapping data, sequencing of RT-PCR products, and Western blotting exclude the Copb gene as a candidate for ru2.     

Corticoliberin Protects Neurons from the Negative Influences of “Dysfunctins” in Living Olfactory Cortex Slices

The protective effects of corticoliberin on living rat olfactory cortex slices during perfusion with dysfunctins extracted from cerebrospinal fluid of drug addicts were studied. Isolated perfusion of slices with medium containing dysfunctins led to irreversible suppression of the amplitude of individual components of focal potentials induced by electrical stimulation of the lateral olfactory tract. The maximum level of depression was seen for the AMPA and NMDA components of EPSP. Preliminary perfusion of slices with medium containing corticoliberin (100 nM) for 15 min partially, and for 30 min completely protected processes mediated by activation of AMPA and NMDA receptor mechanisms from the negative influences of dysfunctins. It is suggested that corticoliberin can induce its protective effects either via its own specific receptors or non-specifically via glutamate receptors. It is also possible that both of these mechanisms act in combination.     

The use of local anaesthetic microinjections to identify central pathways: a quantitative evaluation of the time course and extent of the neuronal block

Summary The time course and extent of local anaesthetic blocks within the spinal cord of cats were evaluated. A monopolar stimulation electrode with the tip lowered into the dorsal columns (DC) 1000 m below cord surface was used to activate antidromically DC fibers at the T13 level and evoke cord dorsum potentials at the level of the lumbar spinal cord. The amplitude of the negative deflection, the N-wave, was determined for various stimulation intensities (stimulation-response-function, SRF). Lidocaine (1%) was microinjected in volumes of 0.5 or 1.0 l into the DC from a glass micropipette 1 mm caudal to the stimulation site. Conduction block was characterized by a reversible shift of the SRFs to higher stimulation intensities. The diameter of the blocked area in the transverse plane was evaluated from threshold intensities and was found to be 0.9±0.1 mm 4 to 30 min after the injection of 0.5 l lidocaine and 1.6±0.36 mm 10 to 45 min after the injection of 1.0 l lidocaine. In the sagittal plane, the diameter of the blocked area following 1.0 l lidocaine was found to be up to 2.8 mm. The DC-block was reversible within 92 min following injection of 1.0 l and 69 min after the injection of 0.5 l lidocaine. The application of the present findings for blocks in other CNS structures is discussed.     

Sprouting of fusimotor neurones after partial denervation of the cat soleus muscle

Summary Normally, motoneurones innervate only the intrafusal fibres of muscle spindles. This is a report of sprouting of motoneurones to innervate extrafusal muscle fibres following partial denervation of the soleus muscle of kittens. In eight newborn animals, the L7 ventral root was cut on one side under anaesthesia and the animals were then allowed to recover. At approximately 100 days of age animals were reanaesthetised and a study made of mechanical properties of motor units whose axons ran in the S1 ventral root and supplied the partially denervated soleus muscle. Evidence was obtained for sprouting of all surviving motoneurones. In addition, in four experiments axons conducting within the range, on stimulation, produced measurable tension. In one experiment, stimulation of one such axon also produced specific fusimotor effects on four afferents identified as coming from primary endings of muscle spindles. The axon was therefore a fusimotor axon. The effect observed on stimulation of the axon suggested a largely dynamic action. Other examples of axons were encountered that on stimulation produced tension, but which could not be specifically associated with spindles. In addition, a number of axons that did not develop tension were shown, on stimulation, to have fusimotor effects that were static in action. It is concluded that in extensively denervated muscles motoneurones may sometimes sprout to innervate extrafusal fibres. The mechanical properties of the extrafusal fibres innervated by such axons were similar to those of ordinary motor units.     

Single unit recordings in the rat pineal gland: Evidence for habenulo-pineal neural connections

Summary Extracellular potentials were recorded in the pineal gland of urethane-anesthetized rats. Two distinct populations of excitable pineal cells were found, the silent cells which were driven by habenula stimulation and the spontaneously active cells. In the former case 17 of the responses (median latency of 1.2 ms) showed a positive-negative potential, and 6 (about 1 ms latency) showed only positive potential of 1–2 ms duration. The remaining cells (114), which could not be driven by habenula stimulation, exhibited spontaneous activity with a firing frequency from less than 1 Hz to greater than 100 Hz with a median firing frequency of 10 Hz.These experiments clearly demonstrate a direct habenulo-pineal fiber pathway and furthermore show that there are neuronal elements in the pineal which are only activated by habenula stimulation.     

The effect of central retinal lesions on optokinetic nystagmus in the monkey

Summary In alert monkeys (Macaca mulatta and fascicularis) the effect of central retinal lesions on fast optokinetic responses was investigated during high velocity optokinetic and visual-vestibular conflict stimulation. The fast component of the optokinetic response manifests itself as a rapid rise in the slow-phase eye velocity after light-on, during high velocity optokinetic stimulation; and a sudden drop in eye velocity after light-off. In contrast, the velocity storage component leads only to gradual changes in eye velocity during continuous optokinetic stimulation and after light-off (optokinetic after-nystagmus).Retinal lesions were placed by laser coagulation in and around the fovea. Responses of the normal and lesioned eye were compared. It was found that central lesions up to 12 deg (fovea diameter 6 deg) had only a negligible effect on fast optokinetic responses. With lesions of more than 25–30 deg diameter centered on the fovea definite fast responses could still be obtained, on average reduced to about 50% of the responses of the normal eye. Some monkeys showed initially no fast optokinetic responses and had, therefore, to be excluded from lesion experiments.The results demonstrate that fast optokinetic responses also can be obtained from extrafoveal areas, i.e. areas which are not generally involved in smooth pursuit eye movements. These results are discussed in relation to reports that the smooth pursuit eye movement system is also used to generate fast optokinetic responses.Supported by Swiss National Foundation for Scientific Research 3.343-2.78 and Deutsche Forschungsgemeinschaft, SFB 200 A2These experiments were performed at the Dept. of Neurology, University of Zürich. A preliminary report of this work was presented at the workshop on Physiological and pathological aspects of eye movements in Habay-la-Neuve (Belgium) and at the 8th Extraordinary Meeting of the Barany Society in Basel (Switzerland)