Effect of serotonin on neuronal background activity in a hemisegment isolated from the infant rat spinal cord

Neuronal background activity was investigated in a hemisegment of the lumbar section of the spinal cord before and after addition of serotonin (5-HT — 1 × 10^–8–10^–4 M) in 14- to 22-day-old rats. Reversible changes in background firing rate were recorded in 50% and 70.6% of dorsal and ventral horn interneurons respectively. Excitatory response predominated; in the dorsal horn, 62.4% of all cells responding to 5-HT showed an excitatory response, 8.4% an inhibitory reaction, and 29.2% a two-stage response. In the ventral horn, an excitatory and two-stage response were recorded in 91.6% and 8.4% of cells respectively. Application of 5-HT induced an increase in firing rate and depolarization in the ventral horn. Findings from this study would point to a primarily excitatory effect of 5-HT on background in segmental neurons.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 3, pp. 335–343, May–June, 1989.     

Rhythmicity of Biopotentials: Its Origin and Involvement in Information Processing

Experimental data and mathematical simulation of a neural network were used to develop ideas concerning the origin of the rhythmicity of biopotentials and its involvement in information processing. Baseline slow oscillations—the primate α rhythm, the α-like rhythms of lower animals, the Δ rhythm of humans and animals, secondary components of sensory evoked potentials or responses to direct brain stimulation, and pathological epileptiform potentials—develop as a result of interactions between excitatory and inhibitory postsynaptic potentials. The main inhibitory transmitter in the brain cortex is γ-aminobutyric acid (GABA). EEG activation in the form of a decrease in the amplitude of baseline oscillations and the appearance of the stress rhythm in the θ band upon exposure to new or biologically significant stimuli is associated with a relative decay of inhibitory hyperpolarization processes. The cholinergic and noradrenergic neurotransmitter systems are substantially involved in the rearrangement of the neural activity associated with EEG activation. An enhancement of high-amplitude baseline oscillations and phasic activity of neurons, i.e., alternation of activation and inhibition of firing, which reflects a relative enhancement of hyperpolarization processes, restricts excitation propagation over brain structures and impedes the fixation of new information. As a result of the decay of the inhibitory processes, EEG activation is accompanied by a higher regularity of neuronal firing and a decrease in entropy in the time distribution of firing in the form of tonic or grouped (in the stress rhythm) discharges. The resulting ordered streams of impulses transfer information, control its propagation, and ensure its fixation and reproduction.__________Translated from Fiziologiya Cheloveka, Vol. 31, No. 3, 2005, pp. 59–71.Original Russian Text Copyright © 2005 by Shul’gina.     

Effects of dopamine on background and evoked activity in interneurons of a spinal cord segment isolated from infant rats

The effects of 1·10^–5–1·10^–3 M dopamine on background and evoked interneuronal-activity was investigated during experiments on a spinal cord segment isolated from 11–18-day old infnat rats. Dopamine induced an increase in background firing activity rate in 52.5% and a reduced rate in 42.5% of the total sample of responding cells. Dopamine exerted a primarily inhibitory effect on interneuronal activity invoked by dorsal root stimulation, as witnessed by the reduced amplitude of the postsynaptic component of field potentials in the dorsal horn together with the fact that invoked activity was depressed in 66.7% of total interneurons responding to dopamine and facilitated in only 33.3% of these cells. All dopamine-induced effects were reversible and dose-dependent. Dopamine-induced effects disappeared after superfusing the brain with a solution containing 0–0.1 mM Ca²⁺ and 2 mM Mn²⁺, suggesting that this response is of transsynaptic origin. In other cells the excitatory or inhibitory action of dopamine also persisted in a medium blocking synaptic transmission; this would indicate the possibility of dopamine exerting depolarizing and hyperpolarizing effects on the interneuron membrane directly. Contrasting responses to dopamine in interneurons may be attributed to the presence of different types of dopamine receptors in the spinal cord.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 21, No. 1, pp. 7–16, January–February, 1989.     

Long-term action of camphor on "audio-sensitive" rats: Electrophysiological study and mathematical modeling of properties of neuronal networks

Krushinskii-Molodkina (KM) strain rats genetically predisposed to audiogenic convulsive reaction were given repeated camphor injections in gradually increasing doses (starting at the minimum threshold level required for seizures to occur) over a 4–5 month period. Animals were able to tolerate camphor at doses 3/2–3 times convulsion threshold level without seizure occurring once habituation to the action of this convulsant had been developed. At the same time, the cortical motor zone of strain KM rats acquired properties typical of an epileptic focus: spontaneous epileptiform firing peaks were noted in the background electrical activity of this zone. A decline in the parameter reflecting efficacy of the mechanisms underlying recurrent inhibition emerged in the cortical motor zone of strain KM rats receiving camphor from calculating the parameters of neuronal network from spectra of summated potentials (using the model of a neuronal network). It is suggested that the development of compensatory processes making it possible to avoid generalized seizure following administration of camphor in large doses is associated with intensification of inhibitory caudate function and attenuated hippocampal excitation.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 193–200, March–April, 1990.     

Post-tetanic changes in intracellular response to direct cortical stimulation

Changes in responses to single stimulations of the cortical surface after tetanization (frequency 50/sec, duration 1–10 sec) were studied in sensorimotor cortical neurons of an unanesthetized rabbit on intracellular and "quasiintracellular" recordings. After tetanization insufficient to generate epileptiform after-discharges, an increase was observed in the amplitude and duration of exciting postsynaptic potentials (EPSP) induced by a single test stimulus. This increase is considered as post-tetanic potentiation (PTP). Its duration did not exceed 1 min. The amplitude of inhibitory postsynaptic potentials (IPSP) showed a considerably smaller increase or did not change or even decreased. The PTP increased with an increase in the strength and duration of the tetanization, reaching especially high values during tetanization sufficiently intensive to evoke epileptiform after-discharges. In this case the response to a single test stimulus was identical to an epileptiform intracellular discharge. The data obtained confirm the important role of PTP of the exciting synapses in the generation of epileptiform after-discharges. A simple model of a neuron network with exciting and inhibiting feedbacks which accounts for the generation of epileptiform activity is examined.Institute of the Brain, Academy of Medical Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 2, No. 6, pp. 601–610, November–December, 1970.     

Effects of noradrenaline on neuronal response induced in the motor cortex by conditioned stimuli

In chronic experiments on cats, the effects were investigated of iontophoretic application of the adrenomimetic ephedrine and the -blocker obsidan (propranolol) on neuronal response induced in the motor cortex by conditioned stimulus presentation during performances of instrumental lever-pressing response. Inhibition of background firing activity and response in most neurons induced by conditioned stimuli was produced by ephedrine, whereas obsidan application enhanced this activity. It was concluded that steady, tonic inhibitory action of the noradrenergic system on background and induced firing activity in cortical neurons takes place during free-ranging behavior. Temporary reinforcement of noradrenergic influences could be an important element in mechanisms of external inhibition during stressful situations, aversive effects, and distractive stimuli.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 5, pp. 680–688, September–October, 1990.     

Frequency potentiation of synaptic response in medial bulbar tegmental neurons to microstimulation of the pontine inhibitory site

Synaptic response to single (2 Hz) and regular (30–50 Hz) stimuli applied to the pontine inhibitory site were recorded in decerebrate cats. A change to regular stimulation was usually accompanied by a rise in the firing index of synaptic discharges and raised amplitude of inhibitory and (to a lesser extent) excitatory postsynaptic potentials. Suppression of background spike activity was observed in some neurons. It was deduced that frequency potentiation makes a considerable contribution to the functional effect of stimulating the inhibitory site, i.e., terminating evoked locomotion.Institute for Information Transmission Studies, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 20, No. 2, pp. 172–180, March–April, 1988.     

Firing rhythmicity in the neocortex in vivo and in vitro under sustained iontophoretic excitation

Extracellular recordings were made from the cat intact neocortex and guinea-pig neocortical slices during microiontophoretic application of amino acid neurotransmitters. Spike train autocorrelation analysis showed a high stability of firing patterns in the intact neocortex. When excitation of a cell was increased in a step-wise manner with glutamate iontophoresis only an enhancement of the rate of firing was observed. The rhythmic component, which was mainly due to periodic multiple discharges, remained up to the highest firing frequencies. In contrast to the in vivo observation, glutamate, aspartate or K⁺ iontophoresis in cortical slices resulted in firing pattern alternations (always from bursts or irregular activity to regular spike firing) as well as an increase in firing rate. In slices the periodic component was typically due to single-spike regularity and its frequency rose with an increase of firing rate. The comparison of autocorrelogram alternations in vivo and in vitro suggests that the temporal organization of spike trains in the intact cortex is under tight external control and is defined mainly by neuronal interactions, whereas virtually all the neurons in vitro are very sensitive to the same iontophoretic influences and their individual outputs easily change according to the excitation (depolarization) level. The coincidence of the lowest frequencies of single-spike regularity in the in vitro preparation (5–7 Hz and 8–10 Hz) with theta- and alpha-rhythms in the electroencephalogram (EEG), and with single unit firing rhythmicity in the whole brain, may represent the basis of a unit-circuit resonance and provide a high stability of these EEG-rhythms.Abbreviations ACF autocorrelation function - BFA background firing activity - EEG electroencephalogram     

Mechanisms of interaction between central neurons and abdominal stretch receptors in the crayfish

Mechanisms of interaction between central and receptor neurons of the crayfish (the principal inhibitory neuron — PIN — and the slow-adapting stretch receptor — SAR) when functioning under different conditions were investigated: during regular spontaneous activity of SAR, grouped discharges of PIN, and regular spontaneous activity of PIN. A close connection was found between the various parameters of the PIN and SAR responses. Adaptation of SAR to the action of adequate, regular repetitive stimulation takes place faster in the presence of stationary background activity of PIN. The appearance and disappearance of SAR spike activity are determined by the ratio between the firing rates of SAR and PIN: at the moment of changeover the neuron with the higher firing rate is predominant.I. P. Pavlov Institute of Physiology, Academy of Sciences of the USSR, Leningrad. Institute of Zoology, Academy of Sciences of the Moldavian SSR, Kishinev. Translated from Neirofiziologiya, Vol. 4, No. 4, pp. 429–438, July–August, 1972.     

Detection and analysis of recurrent inhibition of firing motoneurons in man

During regular firing of "small" motor units, activated during weak voluntary contraction of the human soleus muscle, thick efferent fibers of n. tibialis were stimulated (a small M response was evoked, in which the small units did not participate). Peristimulus histograms of potentials of single motor units were constructed and the effect of stimulation on interspike interval duration was analyzed. The firing rate of the motor units was 4.5–7.6 spikes/sec. Stimulation of the nerve led to a sharp decrease in probability of their discharge or even complete temporary cessation of firing, i.e., it had a well marked inhibitory effect (lasting 10–20 msec). The latent period of inhibition (35–40 msec) was only a little longer than the latent period of the monosynaptic reflex of the soleus muscle. The effect of an inhibitory volley on duration of the interspike interval of the motor units depended on the time when the volley arrived during the interval. Lengthening of the interval was observed only if the inhibitory volley arrived in the second half or at the end of the interval. It is concluded that inhibition of firing of small motor units is due to Renshaw cells, activated on stimulation of axons of large motoneurons. The efficiency of a short (compared with the duration of the interspike interval) inhibitory volley reaching a motoneuron firing at low frequency characteristic of its adequate activation, is discussed.Institute for Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 16, No. 1, pp. 88–96, January–February, 1984.     

Effects of applying electrical stimulation to the locus coeruleus on neuronal activity in the parietal association cortex

It was shown during experiments on cats undergoing surgery under ketamine-induced anesthesia and immobilized with myorelaxin that applying trains of stimuli to the locus coeruleus (LC) produces an effect on 79% of parietal cortex neurons. This manifests as inhibition lasting 300–700 msec or a 16–32% decline in the activity rate of neurons with background activity. Hyperpolarization of 5–7 mV lasting 120–500 msec preceded by a latency of 30–90 msec was noted in such neurons as well as "silent" cells during intracellular recording. Duration of the inhibitory pause in neuronal background activity induced by transcallosal stimulation (TCS) increased by 50–200 msec under the effects of conditioned stimuli applied to the LC. Duration of the IPSP triggered by TCS likewise increased (by 50–100 msec) under the effects of LC stimulation. It was concluded that the effects of stimulating the LC on neuronal activity in the parietal cortex may manifest either directly, as inhibition of background activity and hyperpolarization, or else as modulation of influences exerted by other neurotransmitters.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 4, pp. 486–494, July–August, 1990.     

Effect of somatostatin on neurons of the partially deafferented rabbit amygdala

Changes in spontaneous activity of 291 neurons in the rabbit amygdala were analyzed during microelectrophoretic application of somatostatin under pentobarbital anesthesia. Somatostatin was found both to enhance and to inhibit the spontaneous activity of these cells, by contrast with the exclusively inhibitory effect on spontaneous activity of hypothalamic neurons described previously. After partial chronic deafferentiation of the amygdala, 76% of 103 neurons responded to somatostatin application; 90% of the responding cells, in which the initial spontaneous firing rate was 6–20 spikes/sec, responded by more rapid firing, and only 10% of neurons (with an initial spontaneous discharge frequency of over 20 spikes/sec) showed a decrease in firing rate. Neuronal responses in the amygdala to somatostatin, glutamate, and noradrenalin are compared. Preliminary application of noradrenalin caused an increase in the number of inhibitory responses on subsequent application of somatostatin to the same cell.M. V. Lomonosov Moscow State University. Translated from Neirofiziologiya, Vol. 14, No. 6, pp. 601–607, November–December, 1982.     

Effects of experimentally induced deficiency of catecholaminergic transmission on neuronal activity in the ventrolateral thalamic nucleus

Background activity was investigated in 272 neurons of the ventrolateral thalamic nucleus (VLTN) before and after systemic administration of neuroleptics (haloperidol and droperidol) at cataleptic doses by means of extracellular techniques during chronic experiments on cats. Autocorrelation and spectral analysis revealed regularly-occurring changes in the background activity rate of VLTN neurons, the periodicity of which changed by fractions of seconds (0.2–0.8 sec), seconds (1.5–10 sec), or tens of seconds (12–30 sec). While numbers of neurons with individual types of periodic activity did not exceed 6–8% in intact animals, it did increase to 18–30% after administering neuroleptics. Raised numbers of neurons with two types of regularly occurring processes within a single spike train were also noted. Experimentally-produced data were compared with findings from clinical observations. Quantities of neurons with different variations in the periodicity of their firing activity reached 19–46% in patients with parkinsonism but did not exceed 4–8% in those with torsion dystonia. The genesis of raised rhythmic firing in thalamic neurons occurring with parkinsonism is thought to be associated with impaired catecholaminergic (both dopaminergic and -adrenergic) transmission.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 3, pp. 359–368, May–June, 1990.     

Effects of ketamine on neuronal epileptiform responses in the cat neocortex

The effects of ketamine, an antagonist of NMDA receptors, on the neuronal epileptiform responses evoked by applications of strychnine, penicillin, or bicuculline to the suprasylvian gyrus were studied in cats. Ketamine either exerted no effect, or slightly decreased interictal high-amplitude depolarizing shifts of the membrane potential and depolarizing afterpotentials, which appeared spontaneously or were evoked by intracortical stimulation. Repetitive electrical stimulation of the epileptogenic cortical regions resulted in the appearance of autogenerated ictal activity lasting up to several tens of seconds; this activity was produced against the background of a depolarization of neuronal membranes. After ketamine injections, such stimulations evoked no ictal activity in the neurons, or the discharges became much shorter. The results of our study show that the NMDA-dependent postsynaptic components play a more important role in the development of neocortical ictal activity compared with the interictal activity.Neirofiziologiya/Neurophysiology, Vol. 27, No. 1, pp. 32–35, January–February, 1995.     

Neuronal firing activity in the lateral vestibular nucleus during locomotion in the guinea pig

The effects of spontaneous locomotor activity on neuronal background firing in the lateral vestibular nucleus was investigated during experiments on decerebrate guinea pigs. The onset of rhythmic muscular activity in the extramities was found to produce a rise in the rate of such discharges, which increased from 10–15 to 100 spikes/sec in most neurons. A higher rate occurred as activity began in the ipsilateral forelimb extensor muscles (the stage corresponding to the end of the swing phase and start of the stance phase in the locomotor cycle). The alterations noted in vestibular neuronal activity during locomotion are thought to ensure the background of high anti-graveity muscle tonus against which rhythmic limb movements take place.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 23, No. 5, pp. 536–541, September–October, 1991.     

Changes in membrane potential and postsynaptic potentials evoked by strychnine in neocortical neurons

Intracellular responses of neurons of the suprasylvian fissure to intracortical stimulation before and during topical cortical strychnine application was studied in experiments on immobilized, unanesthetized cats (a local anesthetic was used). Untreated cortical neurons responded to intracortical stimulation with a monosynaptic excitatory postsynaptic potential (EPSP) followed by an inhibitory postsynaptic potential (IPSP). Application of strychnine evoked epileptiform population activity and paroxysmal depolarizations of neuronal membrane potentials (MPs), followed by hyperpolarization. Increased hyperpolarizations, and the prolonged duration of their summation were responsible for an increased MP and reduced or abolished tonic spike activity. Intracellular application (as a result of diffusion from the microelectrode) of ethyleneglycoltetraacetate (EGTA) that blocked the calcium-dependent potassium membrane conductance (gK(Ca)) abolished the hyperpolarization. The development of epileptiform activity was accompanied by reduction of the IPSP, and an increase in the monosynaptic EPSP. The role of gK(Ca) and postsynaptic inhibition in epileptogenesis is discussed.I. I. Mechnikov State University, Odessa. Translated from Neirofiziologiya, Vol. 24, No. 6, pp. 684–691, November–December, 1992.     

Effect of brief inhibitory volley upon human firing motoneurons (experiment and model)

We investigated the effect of reciprocal inhibition upon single firing motoneurons of the human soleus and ex. carpus uln. A computer simulation of the effect of an inhibitory volley upon motoneuron impulse activity was carried out on the basis of our own data and data in the literature [3, 4]. It was shown that the duration of the silent period (SP), i.e., the period of complete cessation of firing as revealed on the peristimulus histogram (PSH), can be altered under the influence of the following factors: mean frequency of background firing (inverse dependence); variance of interspike intervals (ISIs) of background firing (inverse dependence); duration of that portion of an ISI of motoneuron activity during which an inhibitory volley causes a prolongation of the ISI (d); the maximum prolongation of the ISI (x_max). If _maxmax for the briefest ISI within the range of variability in background firing. If x_max>d, the duration of the SP is similar to the duration d of the briefest ISI. To a significant degree, the parameters of the peristimulus histogram thus determine the frequency and variance of ISIs in the background firing and possibly also the individual tendency of the motoneuron to respond to an inhibitory volley by prolongation of the ISI.L. A. Orbeli Institute of Biocybernetics and Biomedical Engineering PAS, Warsaw (Republic of Poland), Institute for Problems of Information Transmission, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 23, No. 4, pp. 463–471, July–August, 1991.     

Involvement of bulbar respiratory and non-respiratory neurons in onset of expiration reflex

It was shown that excitation of high- and low-threshold superior laryngeal afferents triggers reflexes of varying complexity in a considerable proportion of non-respiratory neurons during experiments on cats anesthetized by Nembutal involving stimulation-induced expiration reflex. Systemic alterations in background firing activity were noted during this reflex in "respiratory" neurons; reflex reaction setting in as a result of low-threshold laryngeal afferent activation was also recorded in 22.4% of this group. Oligo- and polysynaptic excitatory connections were found between low-threshold laryngeal afferents and inspiratory beta neurons, P-cells, and laryngeal muscle motoneurons as opposed to inhibitory connections with inspiratory gammaneurons. This article discusses involvement of the neurons investigated in mechanisms of inspiratory inhibition, closure of the vocal chords, and adaptive decline in breathing rate occurring during expiration reflex.A. A. Bogomolets Institute of Physiology, Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 22, No. 5, pp. 670–680, September–October, 1990.     

Static and dynamic activity of cutaneous cold receptors induced by noradrenaline infusion

Experiments on rats showed that cutaneous cold receptors are sensitive to altered blood level of noradrenaline (NA). Both rise in and re-establishing of NA at a new, higher level exert an effect on firing activity in cutaneous cold receptors. When sustained at the raised level, NA alters both static and dynamic activity of cold receptors. The pattern of change (whether excitatory or inhibitory) depends on initial type of receptor activity.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 22, No. 1, pp. 69–75, January–February, 1990.     

Effects of aspartate,substance P,and serotonin on neuronal activity in the central gray substance:In vitro experiments

Effects of aspartate (2 · 10^–5 M), substance P (10^–7–10^–8 M), and serotonin (5-hydroxytryptamine, 5-HT; 5 · 10^–5 M) on the background activity of neurons in the central gray substance (CGS) were studied on slices of the rat midbrain. Aspartate and substance P (transmitters of nociceptive signals), and 5-HT (modulator of transmission of nociceptive influences) were found either to facilitate or to depress the activity of CGS neurons. The predominant effect of substance P or 5-HT applications to neurons of the dorsal CGS part was facilitation, and to neurons of the ventral CGS part, inhibition. The effects of aspartate application on studied CGS neurons were of varying nature, but inhibitory effects were found to prevail.The findings support our earlier hypothesis that assigned the studied neurons to spontaneously discharging inhibitory CGS interneurons, which control the activity of efferent CGS neurons. The role of tested substances in the regulation of CGS neuronal activity and the antinociceptive CGS effects is discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 5, pp. 354–362, September–October, 1993.