Responses of medullary neurons to microstimulation of the "locomotor strip" in cats

Synaptic responses of medullary neurons to stimulation of the bulbar locomotor strip with a current of about 20 µA were studied by an extracellular recording method in mesencephalic cerebellectomized cats. The mean latent period of response of 177 neurons was 3.2 msec. Neurons in which synaptic responses appeared were located in both the lateral and the medial parts of the reticular formation, but short-latency responses were recorded predominantly in the lateral part. In response to a single stimulus 32% of neurons generated a discharge of 2–4 spikes. "Respiratory" neurons were not excited by stimulation of the locomotor point. The results indicate that neurons of the locomotor strip may have an excitatory action not only on each other, but also on neurons located medially. The possible mechanisms of the spread of activity to the superior cervical segments of the spinal cord are discussed.Institute for Problems in Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 13, No. 3, pp. 275–282, May–June, 1981.     

Responses of upper cervical spinal neurons in cats to stimulation of the brain-stem locomotor region at different frequencies

Synaptic responses of neurons in segments C₂ and C₃ to stimulation of locomotor points in the medulla or midbrain were recorded extracellularly in mesencephalic cats. Neurons generating responses with an index of 0.4–0.6 to stimulation with a frequency of 2 Hz maintained this same index at frequencies of 20–60 Hz. The discharge index of many neurons during stimulation at 2 Hz was low, and it increased to 0.4–0.6 when high-frequency stimulation was used. More than half of the cells were excited by stimulation of both ipsilateral and contralateral locomotor points; one-quarter of the neurons responded to stimulation of locomotor points in both medulla and midbrain. The cells studied were located 1.8–4.2 mm from the dorsal surface of the spinal cord. The mean latencies of responses with an index of not less than 0.5 lay within the range 2–30 msec, with a mode of 2–8 msec. Considerable fluctuations of latent period were observed for long-latency responses. The possibility that the neurons studied may participate in the transmission of activity from the locomotor region of the brain stem to stepping generators in the spinal cord is discussed.Institute for Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 15, No. 4, pp. 355–361, July–August, 1983.     

Responses of bulbar neurons to stimulation of locomotor and inhibitory sites in the cat brainstem

Bulbar locomotor and inhibitory sites were located in the pons of mesencephalic decerebellate cats. Rhythmic stimulation of locomotor sites through microelectrodes at the rate of 60 Hz elicited stepping movements in the forelimbs which were halted when the inhibitory sites were rhythmically stimulated. Neuronal response was elicited by single or paired stimulation of locomotor sites at the rate of 1.5 Hz or by applying a series of 2–4 stimuli spaced 2 msec apart to the inhibitory site. Medial neurons generated synaptic responses (postsynaptic potentials or action potentials) to stimulation of the inhibitory site twice as frequently as when the locomotor site was stimulated. Responses in lateral neurons, however, occurred twice as frequently to stimulation of the locomotor site, while IPSP were only observed half as often as EPSP in neurons of both groups. In neurons excited by stimulation of the locomotor site, stimulation of the inhibitory site did not normally produce IPSP. Possible mechanisms underlying the halt of locomotion occurring in response to stimulation of the inhibitory site are discussed.Information Transmission Institute, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 18, No. 4, pp. 525–533, July–August, 1986.     

Responses of spontaneously active spinal neurons to temperature stimulation of the skin

Changes in spontaneous unit activity in the dorsal zones of the spinal cord in response to temperature stimulation of the skin of the thigh and leg were investigated in acute experiments on cats lightly anesthetized with pentobarbital. Two groups of neurons were distinguished by the character of their response. The firing rate of the first group of neurons was changed only in response to cold or warmth. The neurons of the second group responded in opposite ways to the two types of stimulation. Frequency characteristics of spontaneous activity of temperature-sensitive units located in both white and gray matter were determined. In all the lumbar segments their depth was not below the 5th layer of gray matter. Mechanisms of the changes in spontaneous activity and the possible pathways of conduction of temperature sensation are discussed.     

Projections of neurons of the hypothalamic locomotor region to some brainstem and spinal cord structures in the cat

Efferent projections of the thalamic locomotor region were investigated using the horseradish peroxidase technique of retrograde axonal transport. This enzyme was injected into different brain structures. Function was monitored during a micro-injection into the locomotor areas. It was found that direct descending projections from the hypothalamic locomotor region lead mainly to ipsilateral structures and reach the lumbar sections of the spinal cord. Neurons of the locomotor area of the hypothalamus make their major connections with thelocus coeruleus area and the medial brainstem reticular formation. Projections were observed from the hypothalamic locomotor region to the mesencephalic locomotor area and the locomotor strip.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 17, No. 6, pp. 817–23, November–December, 1985.     

Initiation of locomotor activity in spinalized cats by epidural stimulation of the spinal cord]

An area initiating locomotor activity under conditions of the spinal cord surface stimulation (SCS) was found at the upper border of the lumbar enlargement (L4-5 spinal segments). Parameters of the SCS for activation of the spinal stepping generator (SSG) were identified. Activation of the SSG under the SCS was shown to occur because of interaction of the spinal and peripheral mechanisms. Primary role in the SSG initiation during the SCS belongs to the propriospinal system of the dorsolateral funiculi.     

Responses of caudate neurons to acoustic stimulation in cats

Responses of 141 neurons of the caudate nucleus to acoustic stimuli — tones (500 and 2000 Hz) and clicks of different frequency (0.2 and 0.8/sec) and intensity (75, 80, 95 dB) — were recorded extracellularly in chronic experiments on cats. The responses recorded showed great variability with respect to character (phasic, tonic), structure (one or two phases of excitation), latent periods (from 7.5 to 300.0 msec), and burst discharge frequency (from 90 to 800 spikes/sec). Analysis of averaged poststimulus histograms and graphs of the dynamics of the responses showed that responses of 74% of neurons were much better expressed if less frequent stimuli were used: The regularity of the responses and the number of spikes in each response increased. Responses of neurons also increased and acquired a more distinct temporal structure if the intensity of the clicks increased. The character of responses to clicks and tones differed qualitatively in 17% of neurons studied: Phasic excitation arose in response to clicks, tonic changes in spike activity to tones. The particular features of responses of caudate neurons to acoustic stimulation with different parameters are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 12, No. 6, pp. 588–595, November–December, 1980.     

Responses of medullary neurons to moving visual stimuli in the common toad

The concept of coded 'command releasing systems' proposes that visually specialized descending tectal (and pretectal) neurons converge on motor pattern generating medullary circuits and release--in goal-specific combination--specific action patterns. Extracellular recordings from medullary neurons of the medial reticular formation of the awake immobilized toad in response to moving visual stimuli revealed the following main results. (i) Properties of medullary neurons were distinguished by location, shape, and size of visual receptive fields (ranging from relatively small to wide), by trigger features of various moving configural stimulus objects (including prey- and predator-selective properties), by tactile sensitivity, and by firing pattern characteristics (sluggish, tonic, warming-up, and cyclic). (ii) Visual receptive fields of medullary neurons and their responses to moving configural objects suggest converging inputs of tectal (and pretectal) descending neurons. (iii) In contrast to tectal monocular 'small-field' neurons, the excitatory visual receptive fields of comparable medullary neurons were larger, ellipsoidally shaped, mostly oriented horizontally, and not topographically mapped in an obvious fashion. Furthermore, configural feature discrimination was sharper. (iv) The observation of multiple properties in most medullary neurons (partly showing combined visual and cutaneous sensitivities) suggests integration of various inputs by these cells, and this is in principle consistent with the concept of command releasing systems. (v) There is evidence for reciprocal tectal/medullary excitatory pathways suitable for premotor warming-up. (vi) Cyclic bursting of many neurons, spontaneously or as a post-stimulus sustaining event, points to a medullary premotor/motor property.     

Responses of medullary neurons to moving visual stimuli in the common toad

Summary Intracellular recording and labeling of cells from the toad's (Bufo bufo spinosus) medulla oblongata in response to moving visual (and tactual) stimuli yield the following results. (i) Various response types characterized by extracellular recording in medullary neurons were also identified intracellularly and thus assigned to properties of medullary cell somata. (ii) Focussing on monocular small-field and cyclic bursting properties, somata of such neurons were recorded most frequently in the medial reticular formation and in the branchiomotor column but less often in the lateral reticular formation. (iii) Visual object disrimination established in pretectal/tectal networks is increased in its acuity in 4 types of medullary small-field neurons. The excitatory and inhibitory inputs to these neurons evoked by moving visual objects suggest special convergence likely to increase the filter properties. (iv) Releasing conditions, temporal pattern, and refractoriness of cyclic bursting neurons resemble membrane characteristics of vertebrate and invertebrate neurons known to play a role in premotor/motor activity. (v) Integrating functions of medullary cells have an anatomical correlate in the extensive arborizations of their dendritic trees; 5 morphological types of medullary neurons have been distinguished.Abbreviations A stripe moving in antiworm configuration - (W) moving in worm configuration - S square - BMC branchiomotor column - EPSP excitatory postsynaptic potential - IPSP inhibitory postsynaptic potential - RetF medullary reticular formation - RF receptive field - M neurons response properties of medullary neurons - T neurons classes of tectal neurons - TH neurons classes of thalamic/pretectal neurons - tr.tb.d. tractus tecto-bulbaris directus - tr.tbs.c. tractus tecto-bulbaris et spinalis cruciatus     

Transplantation of adult spinal cord grafts into spinal cord transected rats improves their locomotor function

Grafted embryonic central neural tissue pieces can recover function of hemisected spinal cord in neonatal rats and promote axonal growth in adults. However, spinal cord segments from adults have not been used as donor segments for allogeneic transplantation. Here, we utilized adult spinal cord tissue grafts(aSCGs) as donor constructs for repairing complete spinal cord injury(SCI). Moreover, to provide a favourable microenvironment for SCI treatment, a growth factor cocktail containing three growth factors(brain-derived neurotrophic factor, neurotrophin-3 and vascular endothelial growth factor), was applied to the aSCG transplants. We found that the locomotor function was significantly improved 12 weeks after transplantation of aSCGs into the spinal cord lesion site in adult rats. Transplantation of aSCGs combined with these growth factors enhanced neuron and oligodendrocyte survival and functional restoration. These encouraging results indicate that treatment of complete SCI by transplanting aSCGs, especially in the presence of growth factors, has a positive effect on motor functional recovery, and therefore could be considered as a possible therapeutic strategy for SCI.     

C2 spinal cord stimulation induces dynorphin release from rat T4 spinal cord: potential modulation of myocardial ischemia-sensitive neurons

During myocardial ischemia, the cranial cervical spinal cord (C1-C2) modulates the central processing of the cardiac nociceptive signal. This study was done to determine 1) whether C2 SCS-induced release of an analgesic neuropeptide in the dorsal horn of the thoracic (T4) spinal cord; 2) if one of the sources of this analgesic peptide was cervical propriospinal neurons, and 3) if chemical inactivation of C2 neurons altered local T4 substance P (SP) release during concurrent C2 SCS and cardiac ischemia. Ischemia was induced by intermittent occlusion of the left anterior descending coronary artery (CoAO) in urethane-anesthetized Sprague-Dawley rats. Release of dynorphin A (1-13), (DYN) and SP was determined using antibody-coated microprobes inserted into T4. SCS alone induced DYN release from laminae I-V in T4, and this release was maintained during CoAO. C2 injection of the excitotoxin, ibotenic acid, prior to SCS, inhibited T4 DYN release during SCS and ischemia; it also reversed the inhibition of SP release from T4 dorsal laminae during C2 SCS and CoAO. Injection of the kappa-opioid antagonist, nor-binaltorphimine, into T4 also allowed an increased SP release during SCS and CoAO. CoAO increased the number of Fos-positive neurons in T4 dorsal horns but not in the intermediolateral columns (IML), while SCS (either alone or during CoAO) minimized this dorsal horn response to CoAO alone, while inducing T4 IML neuronal recruitment. These results suggest that activation of cervical propriospinal pathways induces DYN release in the thoracic spinal cord, thereby modulating nociceptive signals from the ischemic heart.     

Responses of rabbit visual cortical neurons to intracortical electrical stimulation

Responses of rabbit visual cortical neurons to single and repetitive intracortical electrical stimulation were investigated. The stimulating electrode was located 0.7–1.2 mm away from the recording electrode. Response thresholds to single stimulation were as a rule 150–180 µA, whereas to series of stimuli they were 30–60 µA. The latent period to the first spike averaged 5–15 msec but the probability of the initial discharge was very low, namely 3–6%. With an increase in current intensity the duration of the initial inhibitory pause was increased in half of the neurons responding to it, whereas in the rest it was unchanged. After presentation of series of stimuli spontaneous activity was enhanced for a short time (4–6 sec). In about half of the cells the same kinds of discharge dynamics were observed in response to repetitive stimulation (frequency 0.25 Hz) as in responses to light, but more neurons with sensitization of discharge and fewer "habituating" neurons took part in responses to electrical stimulation. It is postulated that stimulation of a given point of the visual cortex evokes excitation of a local neuron hypercolumn and inhibition of neighboring cell columns.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 15, No. 4, pp. 412–419, July–August, 1983.     

Transcutaneous electrical stimulation of the spinal cord: non-invasive tool for activation of locomotor circuitry in human

A new tool for locomotor circuitry activation in the non-injured human by transcutaneous electrical spinal cord stimulation (tSCS) has been described. We show that continuous tSCS over T11-T12 vertebrae at 5-40 Hz induced involuntary locomotor-like stepping movements in subjects with their legs in a gravity-independent position. The increase of frequency of tSCS from 5 to 30 Hz augmented the amplitude of evoked stepping movements. The duration of cycle period did not depend on frequency of tSCS. During tSCS the hip, knee and ankle joints were involved in the stepping performance. It has been suggested that tSCS activates the locomotor circuitry through the dorsal roots. It appears that tSCS can be used as a non-invasive method in rehabilitation of spinal pathology.     

After-effects of repetitive stimulation in spinal neurons

Spontaneous activity of interneurons before and after repetitive stimulation at 0.1–0.5/sec was recorded in acute experiments on spinal cats and kittens. Using the dynamic selective correlation method a search was made for areas of spontaneous activity with the same distribution of action potentials in time as in the averaged evoked response to a single stimulus. In the case of some neurons portions of the background which correlate reliably in structure with the evoked response repeated at an interval equal to or a multiple of the interval of stimulation. Reproduction of the rhythm of stimulation in the spontaneous activity is intensified with an increase in the total duration of preceding stimulation with the same input and shows positive correlation with the degree of posttetanic potentiation. The facts obtained are evidence of prolonged after-processes in spinal neurons.Institute of Experimental Medicine, Academy of Medical Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 5, No. 3, pp. 272–280, May–June, 1973.     

Responses of spinohypothalamic tract neurons in the thoracic spinal cord of rats to somatic stimuli and to graded distention of the bile duct

Anatomical studies indicate that a relatively large percentage of spinohypothalamic tract (SHT) neurons are located within thoracic spinal segments. The aim of this study was to characterize the responses of SHT neurons in these segments of rats to innocuous and noxious stimulation of the skin and of a visceral structure, the bile duct. In addition, we attempted to determine the trajectories of the axons of the examined neurons within the diencephalon and brainstem. Fifty-three SHT neurons were recorded within segments T8-T13 in urethane anesthetized rats. Each cell was antidromically activated using current pulses < or = 30 microA delivered from the tip of an electrode located within the contralateral hypothalamus. The recording points were located in the superficial dorsal horn (9) and deep dorsal horn (44). All examined SHT neurons had receptive fields on the posterior thorax and anterior and ventral abdomen of the ipsilateral side. Ninety percent of the 41 SHT neurons responded exclusively (13) or preferentially (24) to noxious cutaneous stimuli. Thirteen of 27 (48%) examined units were activated by forceful distention of the bile duct. Response thresholds ranged from 30 to 40 mmHg. Responses incremented as pressures were increased to 50-80 mmHg. The axons of 22 of 28 (79%) examined SHT neurons appeared to cross the midline within the hypothalamus and terminate in the ipsilateral hypothalamus, thalamus or midbrain. The results indicate that SHT neurons in thoracic spinal cord of rats are capable of conveying somatic and visceral nociceptive information from the bile duct directly to targets at various levels of the brain bilaterally.     

Differential susceptibilities of spinal cord neurons to retinoic acid-induced survival and differentiation

In a previous study, we demonstrated trophic effects of vitamin A and its active metabolite, retinoic acid (RA), on perinatal rat spinal cord neurons and astrocytes in vitro. We now report that RA increases the survival of cholinergic neurons without affecting that of GABAergic neurons. These results were supported by measured levels of acetylcholinesterase (AChE), choline acetyltransferase (ChAT), and glutamic acid decarboxylase (GAD) activities, key enzymes of acetylcholine and gamma-aminobutyric acid metabolism, respectively, which showed RA-induced increases in AChE and ChAT levels but no elevations of GAD activity. In contrast to these phenotype-specific effects, most neurons showed RA-induced increases in neuritic outgrowth, density, and silver impregnation. Taken together, these results demonstrate neurotransmitter-specific and generalized effects of RA on developing CNS neurons.