The character of the background spike activity of cortical neurons under the influence of psychotropic drugs]

A comparison was made on alert rabbits between the nature of spike activity of normal cortical neurones and of those after a two-week daily administration of neuroleptics, namely chlorpromazine, trifluoperazine and haloperidol in 1 and 5 mg/kg doses. The groups of neurones did not differ in the mean frequency of firing. However, the use of the main components method and of cluster analysis showed considerable differences between neuronal activity following the action of neuroleptics and that in control animals. The most common effect of neuroleptics consisted in a reduction of the number of low frequency neurones with burst discharges and small dispersion of distribution of interspike intervals. Trifluoperazine and especially haloperidol differed from chlorpromazine in that they brought about an appearance of cortical neurones for which the distribution of interspike intervals had an almost symmetrical form and a mode of 80--170 msec. After the action of haloperidol about a third of the neurones had a mode up to 10 msec. An assumption has been made that the major effect of trifluoperazine and haloperidol consists in an increase in the reverberative activity of the brain.     

Spontaneous Activity in Crustacean Neurons

Single units which discharged with regular spontaneous rhythms without intentional stimulation were observed in the ventral nerve cord by intracellular recording close to the sixth abdominal ganglion. These units were divided into two groups: group A units in which interspike intervals varied less than 10 msec.; group B units in which interspike intervals varied within a range of 10 to 30 msec. Group A units maintained "constant" interspike intervals and could not be discharged by sensory inputs, while the majority of group B units could be discharged by appropriate sensory nerve stimulation. Both group A and B units discharged to direct stimulation when the stimulating and recording electrodes were placed in the same ganglionic intersegment, and directly evoked single spikes reset the spontaneous rhythm. In group B units, presynaptic volleys reset the spontaneous rhythm of some units; but in others, synaptically evoked spikes were interpolated within the spontaneous rhythm without resetting. The phenomenon of enhancement could also be demonstrated in spontaneously active units as a result of repetitive stimulation. It is concluded that endogenous pacemaker activity is responsible for much of the regular spontaneous firing observed in crayfish central neurons, and that interaction of evoked responses with such pacemaker sites can produce a variety of effects dependent upon the anatomical relationships between pacemaker and synaptic regions.     

Dietary Inflammatory Index and Incidence of Cardiovascular Disease in the SUN Cohort

Background

Diet is known to play a key role in atherogenesis and in the development of cardiovascular events. Dietary factors may mediate these processes acting as potential modulators of inflammation. Potential Links between inflammatory properties of diet and the occurrence of cardiovascular events have not been tested previously.

Objective

We aimed to assess the association between the dietary inflammatory index (DII), a method to assess the inflammatory potential of the diet, and incident cardiovascular disease.

Methods

In the prospective, dynamic SUN cohort, 18,794 middle-aged, Spanish university graduates were followed up for 8.9 years (median). A validated 136-item food-frequency questionnaire was used to calculate the DII. The DII is based on scientific evidence about the relationship between diet and inflammatory biomarkers (C-reactive protein, IL-1β, IL-4, IL-6, IL-10 and TNF-α). Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between the DII and incident cardiovascular disease (myocardial infarction, stroke or cardiovascular death).

Results

The risk for cardiovascular events progressively increased with each increasing quartile of DII (p_trend = 0.017). The multivariable-adjusted HR for participants in the highest (most pro-inflammatory) vs. the lowest quartile of the DII was 2.03 (95% CI 1.06–3.88).

Conclusions

A pro-inflammatory diet was associated with a significantly higher risk for developing cardiovascular events.     

Influence of X-ray dose fractionation on the frequency of somatic mutations induced in tradescantia stamen hairs

X-rays were used to investigate the influence of dose fractionation on the induction of pink and colorless somatic mutations in stamen hair cells of Tradescantia clone 02. Inflorescences were exposed to a single acute dose of 60 rad, two acute doses of 30 rad, or three acute doses of 20 rad. The dose rate in all cases was 30 rad/min. Intervals between dose fractions were varied from 35 sec to 48 h and the mutation frequency was compared with that resulting after the single dose of 60 rad. The data show a reduction in mutation frequency for fractionation intervals longer than 15 and 6 min for pink and colorless mutations, respectively, but not for shorter intervals.One interpretation of the data predicts that pink mutation frequencies are reduced by 11% for fraction intervals of from 30 min to 6 h, and that colorless mutation frequencies are reduced by 24% for intervals of from 15 min to 6 h. The corresponding sparing effect of dose fractionation is equal to 6 rad for pink mutations and 9 rad at the colorless mutation endpoint. A calculation has been made which indicates that the percentages of the total repairable (presumably two-hit) damage that is repaired during fraction intervals up to 6 h, are 16 and 35% for pink and colorless mutations respectively.     

Analysis of evoked discharges in hypothalamic neurons to somatosensory,acoustic, and photic stimulation

Single unit activity in the supramammillary, mammillary, and anterior hypothalamic areas in response to acoustic, photic, and sciatic nerve stimulation was recorded in cats anesthetized with chloralose and immobilized with succinylcholine. In response to sensory stimulation the spontaneous firing rate was increased or decreased, and silent neurons were activated. Evoked potentials of the silent neurons had the shortest latent period to acoustic and somatosensory stimulation (15 msec), and rather longer to photic stimulation (30 msec); in some cases their latent period was 200 msec. Histograms of interspike interval distribution showed a maximum for intervals of up to 50 msec. Histograms of spike distribution relative to the beginning of stimulation showed maximal density between 100 and 200 msec. A high degree of convergence of excitation was found on units of the anterior as well as the posterior hypothalamus. Unit responses in the hypothalamus to sensory stimuli of all three modalities are regarded as being of secondary, nonspecific type.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziologiya, Vol. 3, No. 6, pp. 592–598, November–December, 1971.     

Evoked potentials in the visual and association cortex of alert cats during paired uniform stimulation of the lateral geniculate body and pulvinar

Recovery curves of evoked potentials in the association and visual cortex during paired stimulation of the pulvinar in chronic experiments on alert cats were shown to be similar in character. Depression of the test response was observed only if the interval between stimuli was of the order of 10 msec, but if it was 40 msec considerable (2–4 times) facilitation of the second response was observed, mainly on account of an increase in the negative component N₁. Facilitation was less marked if the intervals were from 60 to 100 msec, and they decreased gradually to an interval of 200 msec. The recovery curve of cortical evoked potentials during paired stimulation of the lateral geniculate body differed considerably from the recovery curve during paired stimulation of the pulvinar and was characterized by a gradual increase in amplitude of the second response — from its almost total suppression with an interval of 10 msec to slight facilitation with an interval of 200 msec. If intervals of 10 to 80 msec were used, the test response was restored more slowly in the association cortex than in the visual cortex. The results are discussed from the standpoint of differences in the character of intracortical spread of excitation as a result of activation of geniculo-cortical and pulvinar-cortical pathways of conduction of information.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 16, No. 4, pp. 497–505, July–August, 1984.     

Double discharges in human motoneurons

Potentials of motor units from the trapezius and rectus femoris muscles were recorded with selective needle electrodes during weak and moderately strong voluntary isometric contraction. The sequence of interspike intervals was analyzed. Double discharges (interspike interval not exceeding 20 msec) were found most commonly during recruiting of the motor units, but also at its end. Intervals between double discharges arising while the motor units were firing at a mean rate of 10–18 spikes/sec were outside the limits of statistical scatter of the remaining intervals. Double discharges were recorded chiefly in high-threshold units. The mean interval between double discharges recorded from the trapezius muscle was significantly smaller and the double discharges appeared considerably more often than in the rectus femoris muscle. Comparison of the results of these experiments with those obtained by other workers showed correlation between the mean duration of the interval between the double discharges and the duration of delayed depolarization of the motoneuron; this fact probably plays an important role in the creation of double discharges.     

Unit responses of the sensomotor cortex to paired electrical stimuli

Unit responses of the sensomotor cortex to paired electrical stimulation and visual cortex, applied either simultaneously or after various delays (from 0 to 200 msec) depend on the order of application of the stimuli and on the interval between them. If stimulation of the sensomotor cortex was used in a conditioning role the response continued unchanged when the intervals between stimuli were increased to 200 msec. If, however, stimulation of the sensomotor cortex had a testing role interaction was observed between the stimuli so that responses to both first and second stimuli were blocked; this was exhibited most clearly for intervals of 40–80 msec between stimuli. The blocking effect persisted on some neurons with delays of up to 200 msec between stimuli, while the response of others to both the first and the second stimulus was restored.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 5, No. 6, pp. 628–635, November–December, 1973.     

The Mating Call of Isoperla bipartita Aubert, 1962 (Plecoptera,Perlodidae)

The mating call of Isoperla bipartita is described. The male call is composed of 3–10 groups, each of 1–4 rubs. The times between rubs average 89.52 msec (between first and second), 43.52 msec (between second and third) and 35.28 msec (between third and fourth). The time between two groups averages 180.75 msec and varies from 142 to 290 msec. The female answer is composed of a beat and rub repeated at 479.09 msec intervals on average and interspersed between the male call groups between 94 and 184 msec (mean = 118.11 msec) after the last rub of the male group. The I. bipartita call can be considered as a ‘complex and modified pattern’ because the male produces calls of 1–4 rubs by group and the female answers overlapping the male call by percussion-rubbing-produced signals. Moreover, it is different from other studied Iberian Isoperla calls, being probably a species-specific behavioural pattern.     

Reflection of temporal parameters of an optical stimulus in unitary responses of the sensomotor and visual cortex in cats

Unit activity in the visual (area 17) and sensomotor (areas 4 and 6) cortex in response to an optical stimulus up to 1000 msec in duration was investigated by extracellular recording in acute experiments on cats anesthetized with chloralose (70 mg/kg body weight). Comparative analysis of the types of unitary responses and the durations of the intervals of functional changes showed that: 1) The number of neurons generating on-off responses was about 25% in the visual cortex and 100% in the sensomotor cortex; 2) the intervals of functional changes of the neurons were equal in length to the time intervals of on-off discharges; 3) together with a single time range (200–500 msec), for each area studied specific ranges also exist: from 0 to 200 msec for the visual cortex and from 500 msec and more for the sensomotor cortex; 4) the latent period of after-discharge is equal to the duration of the intervals of functional changes. The results were analyzed from the standpoint of reflection of temporal parameters of optical stimuli by neurons of the sensomotor cortex.A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 7, No. 4, pp. 365–371, July–August, 1975.     

Reactions of neurons of the orbitofrontal cortex to stimulation of optic thalamic nuclei

The reactions of 288 neurons of the orbitofrontal cortex (OFC) to stimulation of the posteroventral (VP), ventral anterior (VA), and reticular (R) nuclei, as well as the median center (CM) of the thalamus, were investigated in acute experiments on cats. OFC neurons can be divided into four groups by their reactions to stimulation of thalamic nuclei: 1) those which respond with an increase in the frequency of the discharges to single and serial stimuli with a frequency of up to 20/sec; 2) those which respond doubtfully to single stimuli with a frequency of 4–12/sec; 3) those which respond with inhibition of the background impulses; 4) those which do not respond to stimulation of the nuclei. Stimulation of the thalamic nuclei evoked responses of OFC neurons with a large scatter of the latent period duration. The responses of neurons to stimulation of the VP (mean latent period 19.1±6.1 msec) had the shortest latent period (sometimes less than 3–4 msec). Reactions with a longer latent period developed upon stimulation of the VA (23.8±7.4 msec) and CM (42.8±12.8 msec). The uniqueness of the links of the OFC with the various optic thalamic nuclei is shown in an analysis of the material obtained and possible methods of the activation of the neurons of this region from thalamic structures are discussed.State Medical Institute, Kemerovo. Translated from Neirofiziologiya, Vol. 3, No. 4, pp. 350–358, July–August, 1971.     

Mapping somatosensory evoked potentials to finger stimulation at intervals of 450 to 4000 msec and the issue of habituation when assessing early cognitive components

Somatosensory evoked potentials (SEPs) to mild electric stimulation of two fingers of the left hand were studied at regular interstimulus intervals (ISIs) of 450, 800, 1400, 2500 and 4000 msec. Habituation was evaluated while the subject was reading a novel so as to virtually ignore the finger stimuli while maintaining steady vigilance levels. Brain SEPs recorded from 25 scalp electrodes were assessed by scatter displays, electronic subtraction, bit-mapped potentials fields, and by calculating theZ estimator and dilation factor. Similar results were obtained with randomly varying ISIs. The P14 farfield and cortical N20 did not change with ISIs. The parietal P27–P45 decreased at ISIs of 800 and 450 msec, but showed no significant habituation at ISIs of 1400, 2500 or 4000 msec. This validated the control conditions used for assessing the early cognitive P30 and P40 to attended target stimuli. The frontal N30 also decremented at the shorter ISIs but still habituated up to ISIs of 2500 msec. The clear dissociation between frontal N30 and parietal P27 at the larger ISIs suggests that they involve at least in part distinct neural generators.     

Pattern and correlation of fast and slow spontaneous unit activity in the visual cortex

Spontaneous unit activity in the visual cortex and its changes during stimulation by continuous light or flashes were investigated in waking rabbits. The study of distributions of adjacent intervals showed that the neurons differ in the ratio of burst (fast, with intervals of up to 15–40 msec) and nonburst (slow) activity and in the character of changes from one type of activity to the other. Of the total number of spikes 63% were outside bursts; the ratio of their number to the number of spikes within bursts consisting of two or of three or more spikes was 27:3:1. The relative stability of the burst structure of spontaneous activity and the limited number of spikes in them (on average 2.4) were demonstrated. Bursts of three or more spikes (mean 3.6) were irregular, and in 79% of them a longer interval (18.6±2.4 msec) was observed before the shortest interval (7.9±0.9 msec). Bursts of spikes of most neurons during photic stimulation contain more spikes with shorter intervals; they also began more frequently with the shortest interval, possibly signifying an increase in the steepness and amplitude of the EPSPs lying at their basis. However, in 20% of neurons spontaneous bursts included more spikes and with shorter intervals than bursts evoked by flash stimulation.Research Institute of Psychiatry, Ministry of Health of the RSFSR, Moscow. Translated from Neirofiziologiya, Vol. 11, No. 4, pp. 311–320, July–August, 1979.     

Motor potentials evoked by paired cortical stimuli

We recorded the motor evoked potentials (MEPs) from the abductor pollicis brevis muscle, after supramaximal electrical transcranial stimulation, and studied the effect of paired transcranial shocks with varying interstimulus time intervals, in 10 normal subjects, 4 patients with median nerve neuropathy and 2 patients with motoneurone disease.In relaxed muscles the amplitude of the MEP evoked by a single shock averaged 30% of the M wave. With intervals from 1 to 2.5 msec 2 shocks evoked one MEP far larger in size than the control MEP (70% of the M wave). With intervals of 10 msec and longer, the 2 shocks evoked 2 independent MEPs; the size of the MEP following the second shock (test) was inversely correlated with the size of the control MEP: the more the control MEP approached the size of the M wave, the smaller the test MEP. Single motor unit records showed that, in the normal subjects and patients with peripheral neuropathy, the same motor unit was activated either by the first or the second shock, whereas in the patients with motoneurone disease it fired twice. In active muscles, the control MEP averaged 70% of the M wave. With intervals of 10 msec and longer the test MEP was markedly suppressed; with 100 msec intervals it fully recovered. In relaxed muscles, by delivering a double shock at a 1.5 msec interval, thus evoking a large MEP, followed by a second double-shock, the test MEP was completely suppressed for a period of 20 msec; it began to recover at 50 msec intervals and fully recovered after 150 msec.These results indicate that: (1) high-threshold spinal motoneurones can profit from temporal summation if double-shocks are delivered at short time intervals; (2) the synchronous excitation of the motoneuronal pool produced by transcranial stimulation is followed by a 20 msec period of absolute inhibition, possibly through a massive activation of the Renshaw system; (3) during voluntary contraction, only a portion of the motoneuronal pool remains refractory, possibly because of the enhanced spinal excitability.     

The glycosylation-dependent interaction of perlecan core protein with LDL: implications for atherosclerosis

Perlecan is a major heparan sulfate (HS) proteoglycan in the arterial wall. Previous studies have linked it to atherosclerosis. Perlecan contains a core protein and three HS side chains. Its core protein has five domains (DI–DV) with disparate structures and DII is highly homologous to the ligand-binding portion of LDL receptor (LDLR). The functional significance of this domain has been unknown. Here, we show that perlecan DII interacts with LDL. Importantly, the interaction largely relies on O-linked glycans that are only present in the secreted DII. Among the five repeat units of DII, most of the glycosylation sites are from the second unit, which is highly divergent and rich in serine and threonine, but has no cysteine residues. Interestingly, most of the glycans are capped by the negatively charged sialic acids, which are critical for LDL binding. We further demonstrate an additive effect of HS and DII on LDL binding. Unlike LDLR, which directs LDL uptake through endocytosis, this study uncovers a novel feature of the perlecan LDLR-like DII in receptor-mediated lipoprotein retention, which depends on its glycosylation. Thus, perlecan glycosylation may play a role in the early LDL retention during the development of atherosclerosis.     

Suppression of visual perception by magnetic coil stimulation of human occipital cortex

Magnetic coil (MC) stimulation percutaneously of human occipital cortex was tested on perception of 3 briefly presented, randomly generated alphabetical characters. When the visual stimulus-MC pulse interval was less than 40–60 msec, or more than 120–140 msec, letters were correctly reported; at test intervals of 80–100 msec, a blur or nothing was seen. Shifting the MC location in the transverse and rostro-caudal axes had effects consistent with the topographical representation in visual cortex, but incompatible with an effect on attention or suppression from an eyeblink. The MC pulse probably acts by eliciting IPSPs in visual stimulus.     

Lens Oscillations in the Human Eye. Implications for Post-Saccadic Suppression of Vision

The eye changes gaze continuously from one visual stimulus to another. Using a high speed camera to record eye and lens movements we demonstrate how the crystalline lens sustains an inertial oscillatory decay movement immediately after every change of gaze. This behavior fit precisely with the movement of a classical damped harmonic oscillator. The time course of the oscillations range from 50 to 60 msec with an oscillation frequency of around 20 Hz. That has dramatic implications on the image quality at the retina on the very short times (∼50 msec) that follow the movement. However, it is well known that our vision is nearly suppressed on those periods (post-saccadic suppression). Both phenomenon follow similar time courses and therefore might be synchronized to avoid the visual impairment.     

Functional characteristics of visual cortical neurons of the cat

The characteristics of neurons in Area 17 of the visual cortex in cats were investigated by extracellular recording of their activity. Unit responses to flashes modulated by intensity and duration (100 µsec-1 sec) were recorded. Of 80 neurons tested, 67.6% were spontaneously active and 32.4% were silent. The threshold responses of the neurons to flashes varied by 7 logarithmic units. The distribution curve of the cells by response thresholds had one maximum corresponding to an energy of the order of 1–10 lm·sec. The time during which the cells could summate excitation did not exceed a mean value of 34 msec. Depending on the latent periods of the visual cortical neurons they can be divided into three groups. The first group includes neurons responding 20–40 msec after stimulation, the second and third neurons responding after 100–120 and 160–180 msec, respectively. Photic stimulation considerably altered the ratio between the numbers of cells generating spikes with high and low frequency. No correlation was found between the sensitivity of the visual cortical cells to light, the latent period of their response, and the critical time of summation. This shows that the cortex contains many duplicate units which are grouped together on the basis of only one of the functional characteristics of their spike response.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 2, No. 2, pp. 173–179, March–April, 1970.     

Motor unit activation patterns during isometric, concentric and eccentric actions at different force levels.

Motor unit activation patterns were studied during four different force levels of concentric and eccentric actions. Eight male subjects performed concentric and eccentric forearm flexions with the movement range from 100 degrees to 60 degrees in concentric and from 100 degrees to 140 degrees elbow angle in eccentric actions. The movements were started either from zero preactivation or with isometric preactivation of the force levels of 20, 40, 60 and 80% MVC. The subjects were then instructed to maintain the corresponding relative force levels during the dynamic actions. Intramuscular and surface EMG was recorded from biceps brachii muscle. Altogether 28 motoneuron pools were analyzed using the intramuscular spike-amplitude frequency (ISAF) analysis technique of Moritani et al. The mean spike amplitude was lower and the mean spike frequency higher in the isometric preactivation phase than in the consequent concentric and eccentric actions. When the movements started with isometric preactivation the mean spike amplitude increased significantly (P<0.001) up to 80% in isometric and concentric actions but in eccentric actions the increase continued only up to 60% (P<0.01). The mean spike frequency in isometric preactivation and in concentric action with preactivation was lower only at the 20% force level (P<0.01) as compared to the other force levels while in eccentric action with preactivation the increase between the force levels was significant (P<0.01) up to 60%. When the movement was started without preactivation the mean spike amplitude at 20% and at 40% force level was higher (P<0.01) in eccentric action than in concentric actions. It was concluded that the recruitment threshold may be lower in dynamic as compared to isometric actions. The recruitment of fast motor units may continue to higher force levels in isometric and in concentric as in eccentric actions which, on the other hand, seems to achieve the higher forces by increasing the firing rate of the active units. At the lower force levels mean spike amplitude was higher in eccentric than in concentric actions which might indicate selective activation of fast motor units. This was, however, the case only when the movements were started without isometric preactivation.     

Unit responses in the anterior zone of the suprasylvian gyrus to peripheral stimuli of different modalities

Unit responses in the anterior zone of the suprasylvian gyrus to visual, electrodermal, and acoustic stimulation were investigated in experiments on unanesthetized cats immobilized with tubocurarine. Electrical activity was recorded from 131 units, 121 of which were spontaneously active. In 65.5% of cells responses consisted of a short or long increase or a decrease in intensity of spike activity. Most cells (58.2%) were monosensory. Responses to visual stimulation were given by 72% of neurons, to electrodermal by 61.6%, and to acoustic by 9.3%. The corresponding latent periods were 20–40, 20–30, and 15–20 msec. Responses of the same neurons to different peripheral stimuli were uniform or they differed in their dynamics. Intracellular recording gave responses in the form of EPSPs (amplitude 4–5 mV, duration 60–80 msec) or, rarely, IPSPs (amplitude 2–3 mV, duration 160–200 msec). The functional organization of the associative cortex and mechanisms of analysis of incoming afferent information are discussed.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 4, No. 4, pp. 368–374, July–August, 1972.