Stochastic versus deterministic variability in simple neuronal circuits: II. Hippocampal slice.

Long time series of Schaffer collateral to CA1 pyramidal cell presynaptic volleys (stratum radiatum) and population spikes (stratum pyramidale) were evoked (driven) in rat hippocampal slices. From the driven CA1 region in normal [K+] perfusate, both population spike amplitude and an input-output function consisting of population spike amplitude divided by the presynaptic volley amplitude were analyzed. Raising [K+] in the perfusion medium to 8.5 mM, slices were induced to spontaneously burst fire in CA3 and long time series of inter-burst intervals were recorded. Three tests for determinism were applied to these series: a discrete adaptation of a local flow approach, a local dispersion approach, and nonlinear prediction. Surrogate data were generated to serve as mathematical and statistical controls. All of the population spike (6/6) and input-output (6/6) time series from the normal [K+] driven circuitry were stochastic by all three methods. Although most of the time series (5/6) from the autonomously bursting high [K+] state failed to demonstrate evidence of determinism, one (1/6) of these time series did demonstrate significant determinism. This single instance of predictability could not be accounted for by the linear correlation in these data.     

Monosynaptic reflexes of the cat spinal cord during the development of insulin hypoglycemia]

Insulin-induced hypoglycemia caused depression of rhythmic monosynaptic EPSP motoneurons of the lumbar cord in acute experiments on narcotized and spinal cats. It was demonstrated that growing depression of monosynaptic transmission was associated with the exhaustion of mediator operative fraction and not with any pre- or postsynaptic delay or inhibition over a period of initial hypoglycemia when the sugar content in the blood fell to the level of 50--60 mg%. The function disturbance of postsynaptic formations of monosynaptic reflex arc of spinal cord occured in more advanced hypoglycemia.     

Spinal and spino-bulbo-spinal neuronal mechanisms of transmission of somatomotor and visceromotor reflexes in the thoracic spinal cord

Early (spinal) and late (spino-bulbo-spinal) responses of interneurons in segments T9–10 to stimulation of the splanchnic and intercostal nerves and the dorso-lateral and ventral funiculi of the spinal cord (at the C3 level) were investigated in experiments on cats anesthetized with chloralose. The experiments showed that interneurons activated by spinal and spino-bulbo-spinal mechanisms differ in their distribution in the dorso-ventral plane of the spinal cord. Cells of layers I–V were excited by spinal pathways only, but those of layers VII and VIII by both spinal and spino-bulbo-spinal or only by the latter. Spino-bulbo-spinal effects were evoked in interneurons by both somatic and visceral afferent waves. A conditioning spino-bulbo-spinal wave evoked deep and prolonged inhibition of late activity induced by somatic or visceral afferent impulses. Early (spinal) activity was inhibited only partially under these circumstances. This inhibition was shown to take place with the participation of supraspinal structures. The possible types of spinal and supraspinal mechanisms of inhibition of early and late activity in spinal neurons are discussed.Institute of Normal and Pathological Physiology, Slovak Academy of Sciences, Bratislava, Czechoslovakia. A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev, USSR. Translated from Neirofiziologiya, Vol. 5, No. 4, pp. 392–400, July–August, 1973.     

Excessive reflexes in spinal cord injury triggered by electrical stimulation

Interaction of electrocutaneous stimulation with an impaired human motor control system may result in unstable reflex loops causing excessive spastic reactions. These contractions are usually excluded from analysis since the presence of spasm is one of the criteria commonly applied for discarding a contraction. They may, however, provide interesting information on the nature of spasticity. The dorsiflexor muscles of four SCI subjects were activated by means of surface electrical stimulation and the isometric ankle moment was measured. Short bursts of constant stimulation frequency at seven different frequencies (8, 12, 16, 20, 25, 33, 50 Hz) triggered spastic reactions in all subjects. The onset times of spastic activity during an electrically elicited contraction shortened with increased stimulation frequency. A stimulation burst may also have a spasticity reduction effect on a subsequent burst, indicating potential short term therapeutic effects of stimulation on spasticity in isometric conditions.     

Oscillations and variability in neuronal systems: interplay of autonomous transient dynamics and fast deterministic fluctuations

Journal of Computational Neuroscience - Neuronal systems are subject to rapid fluctuations both intrinsically and externally. These fluctuations can be disruptive or constructive. We investigate...     

On predicting extinction in simple population models. I. Stochastic linearization

The technique of stochastic linearization derived by Bartlett is used to give an approximate solution to each of three stochastic models of predation. By defining the existence of a quasi-stationary equilibrium distribution of population sizes, the approximate variances and covariances of the joint distribution of population sizes are calculated. The results are used to predict whether prey or predators are likely to become extinct first and the predictions are tested against simulation data. The linearization technique is a good predictor of the outcome of extinction but not of how long it takes.     

Alteration of sensorineural circuits in spinal cord by chronic contact dermatitis

In the present study, eczema-induced alteration of sensorineural circuits of the spinal dorsal horn was investigated. Eczematous lesions resembling atopic dermatitis were induced by repeated application of diphenylcyclopropenone (DCP) onto murine right hind paws. Immunohistochemical labeling of calcitonin gene-related peptide and substance P was increased in the dorsal horn on the DCP-treated side. Expression of calcium binding proteins, calretinin and calbindin-D28K, normally widely seen in dorsal horn interneurons, was up-regulated on the DCP-treated side. E-Cadherin and alpha-N-catenin, synapse-related molecules, were intensely expressed in the spinal dorsal horn of the DCP-treated side. Interestingly, c-Fos positive cells were also significantly increased in laminae I and III of the DCP-treated side. These results suggest an enhanced release of neuropeptides from peripheral afferents and alterations in the sensorineural circuitry of the dorsal horn. These changes may account for the enhanced sensory sensitivity recognized in patients with chronic eczema and atopic dermatitis.     

Effects of oral pergolide mesylate on nociceptive spinal cord reflexes in rats

The effects of orally administered pergolide mesylate on the flexor reflex were evaluated in chronic spinal rats. The mixed D1/D2 agonist pergolide (0.1 to 3.0 mg/kg) produced a dose-related decrease in the magnitude of the flexor reflex elicited by a tetanic stimulus. The effects of pergolide were blocked by haloperidol, demonstrating that the effects of pergolide were mediated through dopamine receptors. In contrast, the selective D2 agonist bromocriptine (3.0 to 30 mg/kg) had no effect on the flexor reflex. The present results are consistent with the interpretation that pergolide produces an antinociceptive action at the spinal cord level by stimulating both D1 and D2 dopamine receptors.     

Mechanisms of establishing long-term fluctuations in the activity of neuronal networks. I. Stochastic uniform neuronal networks

The possibility of generating long-term self-terminating activity lasting some hundreds of milliseconds in neuronal networks with positive (excitatory) feedback was investigated using a computerized mathematical simulation model. This auto-termination is compounded of several factors: stochasticity of the neuronal network, mediating fluctuations in activity level; neuronal interaction, leading either to synchronized discharges and hence of postactivational inhibitory processes, or else to a reorganization of the microstructure underlying neuronal network activity mainly conducive to excitation of neurons with tenuous connections. The likely contribution of these mechanisms to establishing long-term self-terminating activity in the cerebral neuronal networks responsible for different types of programmed rhythmic activity (or generators) is discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 18, No. 3, pp. 382–391, May–June, 1986.     

Permanent alterations of spinal cord reflexes following nerve lesion in newborn rats

Sciatic nerve lesion in newborn rats is known to cause degeneration of a large number of axotomized motoneurones and spinal ganglion cells. Some of the surviving motoneurones exhibit abnormal firing properties and the projection pattern of central terminals of sensory neurones is altered. We report here on long-term changes in spinal cord reflexes in adult rats following neonatal nerve crush. In acutely spinalized and anaesthetized adult rats 4-6 months old in which the sciatic nerve had been crushed on one side at birth, the tibial nerve, common peroneal nerve or sural nerve were stimulated on the reinnervated and control side and reflex responses were recorded from the L5 ventral spinal roots. Ventral root responses (VRRs) to tibial and peroneal nerve stimulation on the side of the nerve lesion were significantly smaller in amplitude representing only about 15% of the mean amplitude of VRRs on the control side. The calculated central delay of the first, presumably monosynaptic component of the VRR potential was 1.6 ms on the control side while the earliest VRR wave on the side of the nerve lesion appeared after a mean central latency of 4.0 ms that seems too long to be of monosynaptic origin. These results suggest that neonatal sciatic nerve injury markedly alters the physiological properties and synaptic connectivity in spinal cord neurones and causes a marked depression of spinal cord responses to peripheral nerve stimulation.     

Monosynaptic reflexes, <Emphasis Type=Italic>c-fos</Emphasis> expression,and NADPH-diaphorase activity in the cat spinal cord: Changes induced by chronic muscle inflammation

Effects of long-term (9 days) experimental unilateral inflammation in the mm. gastrocnemius-soleus (GS), induced by injection of Freund’s complete adjuvant, namely modulation of posterior biceps-semitendinosus (PBSt) monosynaptic reflexes (MSRs), which was induced by chemical activation of high-threshold (groups III and I) muscle afferents, and changes in c-fos expression and NADPH-diaphorase (d) reactivity in the lumbosacral spinal cord, were studied in anemically decapitated and highly (at the C1) spinalized cats. The mean amplitude of the MSRs on the pretreated side did not differ significantly from that on the opposite side. In adjuvant-injected cats, ipsilateral stimulation of nociceptive muscle afferents by KCl injection induced the bilateral enhancement of flexor reflexes. Significant bilateral increases in the mean number of Fos-immunoreactive (Fos-IR) neurons within the L6, L7, and S1 segments (157.5 ± 12.7, 201 ± 18.5, and 205 ± ± 18.6 per section; P < 0.05) were also found in adjuvant-injected cats. A lot of Fos-IR neurons was observed in the marginal zone (lamina I) and the neck of the dorsal horn (laminae V and VI); the highest number of labelled cells was detected in lamina VII. In adjuvant-injected cats, co-distribution of Fos-IR neurons and numerous Fos-IR glia-like cells in the dorsal and ventral horns was also found. Significant increases in the mean number of NADPH-d-reactive cells in lamina VII bilaterally and also in lamina I and in an area around the central canal (lamina X) contralaterally within the L6, L7, and S1 segments (P < 0.05) were also observed. In conclusion, activation of the nociceptive input during long-term inflammation of the GS muscles is associated with differential patterns of c-fos expression and NADPH-d reactivity and also with central neuronal hyperexcitability that contributes to bilateral facilitation of the PBSt MSRs. Neirofiziologiya/Neurophysiology, Vol. 39, No. 3, pp. 222–231, May–June, 2007.     

Relationship between the activity of postsynaptic spinal cord elements and propriospinal and spino-bulbo-spinal reflexes.

The relationship between the activity of the lumbar spinal interneurones and propriospinal (PS) and spino-bulbo-spinal (SBS) efferent reflex responses evoked by somatic (muscle, skin) and splanchnic nerve stimulation was studied in chloralose-anaestetized adult cats. During stimulation of one somatic nerve, the postsynaptic cord elements could be divided into three groups, according to whether their activity was was synchronous with the PS component of the efferent discharge (PS group), with the SBS component (SBS group) or with both (PS-SBS-group). Group SBS and PS-SBS interneurones were localized in the ventral quadrant of the grey matter. On stimulation of different nerves, the same interneurone could in one case respond synchronously with the PS component of the efferent discharge and in another with the SBS component. The membrane of units which did not generate propagated spike potentials during PS or SBS reflex activity was hyperpolarized in this period, or failed to display changes characteristic for postsynaptic inhibition. Convergence of somatic and visceral afferentation was observed in all three groups of postsynaptic elements. In type PS-SBS and SBS units it was massive (occurring in 85% and 100% of the cases respectively). The results confirmed the intimacy of functional contact of PS and SBS systems activated by somatic and visceral afferents.     

The effect of morphine on the input neuronal system of the spinal cord, participating in the formation of nociceptive pressor reflexes]

Effect of morphine applied to the spinal cord segments L4-S2 or C6-tI on pressor reflexes evoked by supramaximal stimulation of radial and tibial nerve with low frequency (I-2 Hz) was studied in anesthetized cats. Only pressor reflexes elicited by excitation of the tibial nerve afferents were suppressed by morphine applied to the L4-S2 segments. This effect was characterized by diminution of amplitude and steepness of the reflexes and by augmentation of their latency. Both the degree and the rate of the reflex suppression were found to enhance with increasing of morphine concentration from 0.02 to 0.5%. When applied to C6-tI segments, morphine did not suppress the pressor reflexes to the tibial nerve stimulation while reflexes to the radial nerve signals were decreased considerably. In addition to this local action of morphine, the effects resulting from it's distant action, namely, some reduction in systemic arterial pressure and an increase of pressor reflexes evoked by afferent signals entering into the spinal cord segments remote from the application region, were found to occur. All these effects were reversed by naloxone (0.2 mg/kg i. v.). It is concluded that along with attenuation of different withdrawal components of the defence reaction, action of morphine on the opiate receptors of some neurons situated near the entrance of afferent signals into the spinal cord results in suppression of the circulatory components of this reaction.     

Electrical activity as a developmental regulator in the formation of spinal cord circuits

Spinal cord development is a complex process involving generation of the appropriate number of cells, acquisition of distinctive phenotypes and establishment of functional connections that enable execution of critical functions such as sensation and locomotion. Here we review the basic cellular events occurring during spinal cord development, highlighting studies that demonstrate the roles of electrical activity in this process. We conclude that the participation of different forms of electrical activity is evident from the beginning of spinal cord development and intermingles with other developmental cues and programs to implement dynamic and integrated control of spinal cord function.     

Fractalkine and minocycline alter neuronal activity in the spinal cord dorsal horn

Fractalkine (FKN) evokes nociceptive behavior in nai ve rats, whereas minocycline attenuates pain acutely after neuronal injury. We show that, in nai ve rats, FKN causes hyperresponsiveness of lumbar wide dynamic range neurons to brush, pressure and pinch applied to the hindpaw. One day after spinal nerve ligation (SNL), minocycline attenuates after-discharge and responses to brush and pressure. In contrast, minocycline does not alter evoked neuronal responses 10 days after SNL or sciatic constriction, but increases spontaneous discharge. We speculate that microglia rapidly alter sensory neuronal activity in nai ve and neuropathic rats acutely, but not chronically, after injury.     

Requirement of N-myc protein down-regulation for neuronal differentiation in the spinal cord

Previous work has indicated that N-myc expression occurs widely in the developing central nervous system, but its level changes dynamically with region- and stage-specificities. We show in the present report that in the developing spinal cord of the mouse, N-myc protein expression takes place in the ventricular zone and reaches its maximum at the outermost layer, but is extinct in the intermediate zone, indicating that N-myc protein is not expressed in mature neurons. We examined the effect of forced, persistent N-myc expression in development of the spinal cord in order to understand the functional significance of N-myc down-regulation. We made embryonic stem (ES) cell lines that constitutively expressed N-myc at a high level, then produced mouse embryo chimeras with a high contribution of the ES cells. The majority of the chimeras developed to day 12 with normal gross morphology, but in these chimeras neuronal differentiation in the spinal cord was perturbed at the histological level. Intermediate zones and ventral horns were formed, but the expression of N-CAM and neurofilaments was diminished. Chimeras using β-galactosidase-expressing recipient embryos indicated that inhibition of the neuronal differentiation was a cell-autonomous effect of persistent N-myc expression. These observations indicate that N-myc down-regulation in individual cells is required for full differentiation of neurons.