Participation of nonsegmentary neurons of the spinal cord in execution of presynaptic control

Experiments were carried out on cats six days after complete transection of the spinal cord. Cord dorsum potentials (CDP) were recorded in the vicinity of the third lumbar segment during stimulation of the isolated dorsolateral funiculus (DLF). The CDP consist of a rapid monophasic potential (which apparently reflects antidromic excitation of the cells of Clarke's column) and two subsequent slow negative waves, which are replaced by a long positive oscillation. In form, time characteristics, and behavior during thythmic stimulation, this potential differs considerably from the CDP recorded during stimulation of the afferent nerves. The presence of a positive phase of the CDP indicates that stimulation of the DLF evokes primary afferent depolarization (PAD). Stimulation of the DLF causes inhibition of the CDP evoked by stimulation of the afferent nerve. The time course of this inhibition corresponds to the time course of presynaptic inhibition. It is demonstrated that stimulation of the afferent nerve (n. femoralis) inhibits slow components of the CDP evoked by stimulation of the DLF. This inhibition reaches a maximum at the 16th millisecond; its duration exceeds 300 msec. Stronger and more prolonged inhibition of the same components is observed when both the conditioning and the testing stimuli are administered to the DLF. Since primary afferents do not take part in CDP emergence during stimulation of the DLF, it may be hypothesized that the observed inhibition develops as a result of depolarization of interneuron axon terminals.Dnepropetrovsk State University. Translated from Neirofiziologiya, Vol. 2, No. 5, pp. 520–527, September–October, 1970.     

Cortical Presynaptic Control of Dorsal Horn C–Afferents in the Rat

Lamina 5 sensorimotor cortex pyramidal neurons project to the spinal cord, participating in the modulation of several modalities of information transmission. A well-studied mechanism by which the corticospinal projection modulates sensory information is primary afferent depolarization, which has been characterized in fast muscular and cutaneous, but not in slow-conducting nociceptive skin afferents. Here we investigated whether the inhibition of nociceptive sensory information, produced by activation of the sensorimotor cortex, involves a direct presynaptic modulation of C primary afferents. In anaesthetized male Wistar rats, we analyzed the effects of sensorimotor cortex activation on post tetanic potentiation (PTP) and the paired pulse ratio (PPR) of dorsal horn field potentials evoked by C–fiber stimulation in the sural (SU) and sciatic (SC) nerves. We also explored the time course of the excitability changes in nociceptive afferents produced by cortical stimulation. We observed that the development of PTP was completely blocked when C-fiber tetanic stimulation was paired with cortex stimulation. In addition, sensorimotor cortex activation by topical administration of bicuculline (BIC) produced a reduction in the amplitude of C–fiber responses, as well as an increase in the PPR. Furthermore, increases in the intraspinal excitability of slow-conducting fiber terminals, produced by sensorimotor cortex stimulation, were indicative of primary afferent depolarization. Topical administration of BIC in the spinal cord blocked the inhibition of C–fiber neuronal responses produced by cortical stimulation. Dorsal horn neurons responding to sensorimotor cortex stimulation also exhibited a peripheral receptive field and responded to stimulation of fast cutaneous myelinated fibers. Our results suggest that corticospinal inhibition of nociceptive responses is due in part to a modulation of the excitability of primary C–fibers by means of GABAergic inhibitory interneurons.     

On mechanisms of depression in pathways of presynaptic inhibition

We investigated inhibition of the N₁-component of the spinal cord dorsal potential (CDP) evoked by experimental stimulation of the n. peroneus in spinal cats. Stimulation was carried out following two conditioning stimuli administered at different time intervals to the same or different cutaneous nerves. The interval between the last conditioning stimulus and the experimental one remained constant (20 msec). It is demonstrated that there is no dependence between weakening of inhibitory action of the second conditioning stimulus and inhibition of the dorsal horn interneurons excited by it that generate the N₁-component of the CDP. It is hypothesized that mechanisms which act on the principle of negative feedback are present in the vincinity of the synaptic junctions of cutaneous afferent fibers with neurons of the substantia gelationsa, and that these mechanisms restrict the development of presynaptic inhibition during inflow of a series of afferent impulses into the cord.Dnepropetrovsk State University. Translated from Neirofiziologia, Vol. 1, No. 3, pp. 253–261, November–December, 1969.     

Physiological properties of afferents and synaptic reorganization in the rat cerebellum degranulated by postnatal X-irradiation.

Elimination of most granule, basket, and stellate interneurons in the rat cerebellum was achieved by repeated doses of low level x-irradiation applied during the first two weeks of postnatal life. Electrical stimulation of the brain stem and peripheral limbs was employed to investigate the properties of afferent cerebellar pathways and the nature of the reorganized neuronal synaptic circuitry in the degranulated cerebellum of the adult. Direct contacts of mossy fibers on Purkinje cells were indicated by short latency, single spike responses: 1.9 msec from the lateral reticular nucleus of brain stem and 5.4 msec from ipsilpateral forelimb. These were shorter than in normal rats by 0.9 and 2.1 msec, respectively. The topography of projections from peripheral stimulation was approximately normal. Mossy fiber responses followed stimulation at up to 20/sec, whereas climbing fiber pathways fatigued at 10/sec. The latency of climbing fiber input to peripheral limb stimulation in x-irradiated cerebellum was 23 +/- 8 (SD) msec. In x-irradiated rats, the climbing fiber pathways evoked highly variable extracellular burst responses and intracellular EPSPs of different, discrete sizes. These variable responses suggest that multiple climbing fibers contact single Purkinje cells. We conclude that each type of afferent retains identifying characteristics of transmission. However, rules for synaptic specification appear to break down so that: (1) abnormal classes of neurons develop synaptic connections, i.e., mossy fibers to Purkinje cells; (2) incorrect numbers of neurons share postsynaptic targets, i.e., more than one climbing fiber to a Purkinje cell; and (3) inhibitory synaptic actions may be carried out in the absence of the major inhibitory interneurons, i.e., Purkinje cell collaterals may be effective in lieu of basket and stellate cells.     

Physiological properties of afferents and synaptic reorganization in the rat cerebellum degranulated by postnatal x-irradiation

Elimination of most granule, basket, and stellate interneurons in the rat cerebellum was achieved by repeated doses of low level x-irradiation applied during the first two weeks of postnatal life. Electrical stimulation of the brain stem and peripheral limbs was employed to investigate the properties of afferent cerebellar pathways and the nature of the reorganized neuronal synaptic circuitry in the degranulated cerebellum of the adult. Direct contacts of mossy fibers on Purkinje cells were indicated by short latency, single spike responses: 1.9 msec from the lateral reticular nucleus of brain stem and 5.4 msec from ipsilateral forlimb. These were shorter than in normal rats by 0.9 and 2.1 msec, respectively. The topography of projections from peripheral stimulation was approximately normal. Mossy fiber responses followed stimulation at up to 20/sec, whereas climbing fiber pathways fatigued at 10/sec. The latency of climbing fiber input to peripheral limb stimulation in x-irradiated cerebellum was 23 ± 8 (SD) msec. In x-irradiated rats, the climbing fiber pathways evoked highly variable extracellular burst responses and intracellular EPSPs of different, discrete sizes. These variable responses suggest that multiple climbing fibers contact single Purkinje cells. We conclude that each type of afferent retains identifying characteristics of transmission. However, rules for synaptic specification appear to break down so that: (1) abnormal classes of neurons develop synaptic connections, i.e., mossy fibers to Purkinje cells; (2) incorrect numbers of neurons share postsynaptic targets, i.e., more than one climbing fiber to a Purkinje cell; and (3) inhibitory synaptic actions may be carried out in the absence of the major inhibitory interneurons, i.e., Purkinje cell collaterals may be effective in lieu of basket and stellate cells.     

Effects of prenatal hypoxia on expression of amyloid precursor protein and metallopeptidases in the rat brain

Summary In the present study we have investigated the effect of prenatal hypoxia on expression of amyloid precursor protein (APP) and some metallopeptidases, which regulate β-amyloid peptide (Aβ) levels (neprilysin (NEP) and endothelin-converting enzyme (ECE-1)) in the cortex of rats during different periods of postnatal development. We have found that the level of APP in the sensorimotor cortex (SMC) of rats, analysed by Western blotting, increases from days 1 to 5 of postnatal development and then steadily decreases with age, with the most dramatic decline in the period from day 180 to 600. In the cortex of rats subjected to prenatal hypoxia on day 13.5 of embryogenesis, the postnatal levels of APP were higher than in the control. Secretion of the soluble form of APP (sAPP) by α-secretase was found to be the most active on day 30 of postnatal development and there was a significant decrease in the production of sAPP after prenatal hypoxia. NEP was found to be expressed in the cortex of rats only at the early stages of postnatal development and it was barely detectable in adult rats. The decline of NEP levels during ageing might contribute to accumulation of Aβ in later life in humans. Prenatal hypoxia resulted in a significant decrease of NEP expression on day 10, but its level was recovered when animals were preconditioned to mild hypoxia. A similar phenomenon was observed when the expression of ECE-1 was analysed. Overall, prenatal hypoxia leads to significant changes in the levels of APP and expression of metallopeptidases involved in amyloid metabolism during all postnatal life and preconditioning to hypoxia appeared to be neuroprotective.     

Effect of local cooling of the cortex on evoked potentials in the reticular formation in response to somatosensory stimulation

Potentials evoked in nuclei of the reticular formation by electrodermal stimulation of the limbs were investigated in acute experiments on unanesthetized, immobilized rats during cooling of the somatosensory cortex in the area of representation of one forelimb. Evoked potentials in the reticular formation were found to depend on the degree of cold inhibition of the cortical primary response to the same stimulation. The peak time of the main negative wave increased from 40–50 to 60–80 msec with a simultaneous decrease in its amplitude or its total disappearance in the case of deep cooling of the cortex. Cooling of the cortex had a similar although weaker effect on the earlier wave of the evoked potential with a peak time of 14 msec, recorded in the ventral reticular nucleus. In parallel recordings of potentials evoked by stimulation of other limbs they remained unchanged at these same points of the reticular formation or were reduced in amplitude while preserving the same temporal parameters. Cooling of the cortex thus selectively delays the development and reduces the amplitude of the response to stimulation of the limb in whose area of representation transformation of the afferent signal into a corticofugal volley is blocked. Consequently the normal development of both late and early components of the potential evoked in the reticular formation by somatic stimulation requires an additional volley, descending from the cortex, and formed as a result of transformation of the same afferent signal in the corresponding point of the somatosensory cortex.I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Academy of Sciences of the USSR, Leningrad. Translated from Neirofiziologiya, Vol. 13, No. 1, pp. 32–38, January–February, 1981.     

Impulse activity of the bulbar cardiovascular neurons during myocardial ischemia and stimulation of the cortical sensorimotor zone

In acute experiments on cats performed under nembutal anesthesia the stimulation of sensorimotor zone in cerebral hemisphere cortex changed the impulse activity of interneurons of bulbar cardiovascular centre and not of the afferent neurons. The analysis of the activity of afferent neurons and interneurons has shown a decrease in coordination between the reaction of these cells to the development of ischemic myocardial lesions during the cortex stimulation. In these conditions bulbar cardiovascular neurons could both increase and decrease the impulse activity. These changes seem to be the reason for the growing incidence of idioventricular ischemic arrhythmias during cortical stimulation.     

Postnatal physiological development of rats after acute prenatal hypoxia

The aim of study was to investigate the physiological development of the brain and behaviour in rats subjected to prenatal hypoxia on the 13.5th day of embryogenesis. We have found that such rats manifested a delayed physiological development and a change in nervous tissue of the sensorimotor cortex, as well a disturbed formation of motor responses during the first month of postnatal ontogenesis. During maturation these modifications were in part compensated, however we observed a decrease of the rats' ability to learn new forepaw movements. The destruction of the brain tissue and the modification of neurons composition in the sensorimotor cortex correlated with changes of behaviour at different stages of ontogenesis. Thus, changes of the conditions under which an organism develops during embryogenesis, predetermine a disturbance in ontogenesis and the learning ability.     

Neuronal and synaptic mechanisms of cortical inhibition

The latent periods, amplitude, and duration of IPSPs arising in neurons in different parts of the cat cortex in response to afferent stimuli, stimulation of thalamocortical fibers, and intracortical microstimulation are described. The duration of IPSPs evoked in cortical neurons in response to single afferent stimuli varied from 20 to 250 msec (most common frequency 30–60 msec). During intracortical microstimulation of the auditory cortex, IPSPs with a duration of 5–10 msec also appeared. Barbiturates and chloralose increased the duration of the IPSPs to 300–500 msec. The latent period of 73% of IPSPs arising in auditory cortical neurons in response to stimulation of thalamocortical fibers was 1.2 msec longer than the latent period of monosynaptic EPSPs evoked in the same way. It is concluded from these data that inhibition arising in most neurons of cortical projection areas as a result of the arrival of corresponding afferent impulsation is direct afferent inhibition involving the participation of cortical inhibitory interneurons. A mechanism of recurrent inhibition takes part in the development of inhibition in a certain proportion of neurons. IPSPs arise monosynaptically in 2% of cells. A study of responses of cortical neurons to intracortical microstimulation showed that synaptic delay of IPSPs in these cells is 0.3–0.4 msec. The length of axons of inhibitory neurons in layer IV of the auditory cortex reaches 1.5 mm. The velocity of spread of excitation along these axons is 1.6–2.8 msec (mean 2.2 msec).A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 16, No. 3, pp. 394–403, May–June, 1984.     

Contribution of antidromic efferent-fiber excitation to mass spinal potentials in the cat

The contribution of antidromic excitation of motoneurons to cord dorsum potentials (CDP) was studied in the spinal cord of anesthetized cats. It was shown that stimulation of ventral roots (VR) or peripheral nerves following deafferentiation of a number of segments by crosscutting of dorsal roots on the dorsal surface evokes appreciable positive-negative CDP (VR-CDP). Under intact conditions, VR effects of antidromic stimulation of efferent fibers brings appreciable input to the initial "fast" CDP component (the "afferent" peak); input values for the main mixed nerves of the hindlimb are presented. After conditioning stimulation of a mixed nerve, VR-CDP undergo inhibition with two maximums, associated with blocking of the effects of antidromic excitation of efferents by orthodromic mono- and polysynaptic reflex discharges of motoneurons. The hypothesis that intactness of efferents in nerves under stimulation can be determined from an analysis of initial CDP components is stated.Scientific-Research Institute of Biology, Dnepropetrovsk State University, Dnepropetrovsk. Translated from Neirofiziologiya, Vol. 23, No. 6, pp. 655–661, November–December, 1991.     

Establishment of the afferent function of the striatum in the rabbit during early ontogenesis

The study is dedicated to electrophysiological analysis of development of the caudate nucleus afferent function in rabbits in early postnatal ontogenesis. By amplitude-temporal parameters of the evoked potentials (EPs) of the caudate nucleus, recorded in response to stimulation of afferent inputs from the cortical regions (motor and limbic) and substantia nigra, similar dynamics of these afferent pathways functional maturation is revealed from the beginning of functioning (in the age of 3-5 days) to the definitive level (by the 30th day of life). The most significant changes of the amplitude-temporal parameters of the evoked potential, particularly of latencies are observed during the 3d week of postnatal life. On the basis of the obtained data, the conclusion is made on the formation of a common system of striatum sensory integration in the 3d-4th week of rabbits life. This age period is considered as critical.     

Formation of "caudate spindles" in the rabbit sensomotor cortex during ontogeny

Electrical activity of the sensomotor and visual areas of the neocortex during stimulation of the caudate nucleus was recorded in young rabbits aged 3–60 days and in adults. Single stimulation of the caudate nucleus was found to cause the appearance of characteristic bursts of spindle-like rhythmic activity ("caudate spindles"), described previously in cats and monkeys, in the adult rabbit cortex. The latent period of the caudate spindle was about 200 msec, its duration 1–3 sec, and the frequency of its oscillations of the order of 12 Hz. Caudate spindles were most marked in the sensomotor cortex of the ipsilateral hemisphere. In rabbits under 10 days old caudate spindles were not found even if the intensity of stimulation was increased many times. Starting from the age of 15 days bursts of rhythmic activity resembling caudate spindles, but with lower frequency (about 8 Hz), longer latent period (up to 350 msec), and also with a higher threshold, appeared in the sensomotor cortex. The definitive type of caudate spindles was established toward the end of the first month of postnatal life, corresponding to the time of formation and complication of conditioned-reflex activity in developing animals.Brain Institute, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 17, No. 1, pp. 11–15, March, 1985.     

Electrocorticographic development of epileptogenic foci in the occipital region of the rat cerebral cortex

The development of cortical penicillin foci in the occipital region was studied in rats whose ages ranged from five days up to the adult age. The local application of penicillin induced the formation of an epileptogenic focus for the first time at the age of seven days. With advancing age, the amplitude of focal discharges increased, the duration of the individual components of the discharge shortened, its originally negative-positive configuration changed to a triphasic form and in the third week of life initial positivity, for a time, become the dominant component of the discharge. Projection of the discharges to the contralateral hemisphere was found to be inconstant in the second postnatal week, but appeared regularly from the age of 14 days. Synchronization of the discharges of two symmetrical foci was very poor in 7-day-old young, but improved noticeably by the 14th day; it was never complete, however, even in adulthood. The activity of symmetrical foci changed spontaneously to ECoG seizures, which were most common in 7-day-old young (in which ictal activity was usually not generalized, however) and were least frequent in 14-day-old animals. Focal discharges could not be reliably triggered by electrical stimulation of the contralateral cortex until the age of 18 days and later. The occipital part of the cortex develops somewhat later than the sensorimotor, frontal region, and during its development there also appeared phenomena which are not present in the frontal cortex.     

Unit responses of the first and second somatosensory cortical areas to peripheral,thalamic, and cortical stimulation

Unit responses of the first (SI) somatosensory area of the cortex to stimulation of the second somatosensory area (SII), the ventral posterior thalamic nucleus, and the contralateral forelimb, and also unit responses in SII evoked by stimulation of SI, the ventral posterior thalamic nucleus, and the contralateral forelimb were investigated in experiments on cats immobilized with D-tubocurarine or Myo-Relaxin (succinylcholine). The results showed a substantially higher percentage of neurons in SII than in SI which responded to an afferent stimulus by excitation brought about through two or more synaptic relays in the cortex. In response to cortical stimulation antidromic and orthodromic responses appeared in SI and SII neurons, confirming the presence of two-way cortico-cortical connections. In both SI and SII intracellular recording revealed in most cases PSPs of similar character and intensity, evoked by stimulation of the cortex and nucleus in the same neuron. Latent periods of orthodromic spike responses to stimulation of nucleus and cortex in 50.5% of SI neurons and 37.1% of SII neurons differed by less than 1.0 msec. In 19.6% of SI and 41.4% of SII neurons the latent period of response to cortical stimulation was 1.6–4.7 msec shorter than the latent period of the response evoked in the same neuron by stimulation of the nucleus. It is concluded from these results that impulses from SI play an important role in the afferent activation of SII neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 8, No. 4, pp. 351–357, July–August, 1976.     

Neuronal responses of the rate somatosensory cortex transplanted into the vibrissae representation field of the neocortex to the electrical stimulation of the recipient brain

Neuronal responses of the rat somatosensory cortex grafted into damaged host barrel field to electrical stimulation of the host brain were investigated extracellularly in rats under light pentobarbital anaesthesia. The following structures of the host brain were stimulated: ventrobasal complex and posterior thalamic nuclei, ipsilateral area of vibrissae representation in the sensorimotor cortex and contralateral barrel field. Reactivity of the grafted neurones was lower, than in the intact barrel field, but the mean latencies of responses were not significantly different. Stimulation of the thalamic nuclei was more effective than that of the cortical areas both in grafted and intact barrel fields. Posttetanic depression after repetitive stimulation was often observed in the grafts, while posttetanic potentiation was more usual for the intact barrel field. The data show the sources of some functional afferent inputs to the grafts which may be responsible for neuronal reactions to somatosensory stimulation of the host animal.     

Cortical influences on neurons of the lateral reticular nucleus responding to noxious stimuli

The effect of frontoparietal sensorimotor (FPSM) cortex stimulation on both the spontaneous and the noxious evoked activity of neurons in the lateral reticular nucleus (LRN) was tested in barbiturate-anesthetized rats. Ninety-three LRN neurons that responded to a noxious heat stimulus (HS) were recorded (72% antidromically fired from the cerebellum). Of these, 66 neurons altered their spontaneous firing rates in response to cortical stimulation. Two patterns of responses were found: either an excitation followed by a suppression of spontaneous activity (52 neurons), or a pure suppression of spontaneous activity lasting 50-400 msec (14 neurons). In 46 of these neurons, it was found that cortical stimulation reduced HS-evoked activity to near the baseline level. Furthermore, it was found that when applied after a prolonged cortical stimulation, the HS was ineffective. It is concluded that FPSM cortex can influence nociceptive information in LRN neurons that respond to its stimulation, possibly interfering with the mechanisms underlying stimulation-produced analgesia (SPA). In this context, it is proposed that the cortex can modulate the activity of LRN neurons that activate, through local loops, a descending antinociceptive system and also a separate projection system to the cerebellum.     

Cortical Influences on Neurons of the Lateral Reticular Nucleus Responding to Noxious Stimuli

The effect of frontoparietal sensorimotor (FPSM) cortex stimulation on both the spontaneous and the noxious evoked activity of neurons in the lateral reticular nucleus (LRN) was tested in barbiturate-anesthetized rats. Ninety-three LRN neurons that responded to a noxious heat stimulus (HS) were recorded (72% antidromically fired from the cerebellum). Of these, 66 neurons altered their spontaneous firing rates in response to cortical stimulation. Two patterns of responses were found: either an excitation followed by a suppression of spontaneous activity (52 neurons), or a pure suppression of spontaneous activity lasting 50-400 msec (14 neurons). In 46 of these neurons, it was found that cortical stimulation reduced HS-evoked activity to near the baseline level. Furthermore, it was found that when applied after a prolonged cortical stimulation, the HS was ineffective. It is concluded that FPSM cortex can influence nociceptive information in LRN neurons that respond to its stimulation, possibly interfering with the mechanisms underlying stimulation-produced analgesia (SPA). In this context, it is proposed that the cortex can modulate the activity of LRN neurons that activate, through local loops, a descending antinociceptive system and also a separate projection system to the cerebellum.     

Responses of parietal associative neurons to stimulation of primary sensory areas

Responses of 251 neurons in the anterior part of the middle suprasylvian gyrus to stimulation of primary sensory (auditory, visual, somatosensory) areas and also to acoustic, visual, and somatosensory stimuli were studied in acute experiments on cats anesthetized with chloralose (40 mg/kg) and pentobarbital (20 mg/kg). Three groups of neurons were distinguished by their responses to stimulation of the primary sensory areas: those responding by an increased firing rate (117) or by inhibition (35) and those not responding (99). Responses of 193 neurons to stimulation of the peripheral afferent systems were analyzed. Neurons of the parietal associative cortex responded more frequently to cortical stimulation than to peripheral. By the duration of the latent period of their response to cortical stimulation the neurons were divided into three groups: those with short (less than 20 msec), medium (20–30 msec), and long latent periods (over 30 msec). The first group was the largest.Kemerovo State Medical Institute. Translated from Neirofiziologiya, Vol. 4, No. 5, pp. 524–530, September–October, 1972.     

Electrical activity of thalamocortical association systems in postnatal ontogeny of the cat

Electrical responses to somatic, photic, and acoustic stimulation in the sensomotor, parietal, temporal, and occipital regions of the cortex were studied in the nucleus lateralis posterior and nucleus ventralis lateralis of the thalamus by recording averaged evoked potentials in kittens (aged 3 to 41 days) anesthetized with pentobarbital. A definite order of maturation of afferent inputs into cortical association areas was demonstrated. The parietal cortex was shown to become polysensory before the sensorimotor cortex. It is suggested that the nucleus lateralis posterior is the main thalamic nucleus responsible for conduction of visual information to the cortex in kittens during the first month of life. Incorporation of this nucleus into the system conducting somatic impulsation to the sensorimotor cortex takes place by the age of 3 weeks.A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 14, No. 5, pp. 476–482, September–October, 1982.