The characteristics of trace rhythm reproduction by the neurons of the rabbit sensorimotor cortex in the aftereffect of periodic stimulation]

Trace rhythm recruitment (TRR)--CR analogue to time was studied appearing in response to prolonged electrocutaneous stimulation of the forelimb of the alert rabbit with the frequency 0.5-1-2 Hz. The activity was recorded of 180 cells of the sensorimotor cortex before (80) and after (100) periodical stimulation during 10-20 min. The first series of rhythmic stimulation led to a short-term TRR of the stimulation frequency, the following series formed a clear TRR, preserved for several days. The possibility was revealed of "relearning" of neurones at stimulation rhythm change. The ability of TRR phenomenon of extinguishment, prolonged preservation and reproduction of traces, "relearning" brings it nearer to the processes, analogous to the temporal connection. The ability to reveal distinctly and to quantitatively estimate the characteristics of the applied stimulus fixated by the neurones, makes this model perspective for comparable study of the memory traces at the neuronal level in the animals of various ages.     

Age-specific morphological-functional characteristics of the rabbit's hippocampal neurons during conditioning

Formation of trace rhythm recruitment (an analogue of conditioned time reflex) was studies in CA3 hippocampal neurons of alert young (less than one year), old (54-65 months), and very old rabbits after a prolonged (10-20 min) electro-cutaneous stimulation of a forelimb with the frequency of 0.5-1 Hz. Comparative analysis of neuronal spike activity in young and old rabbits showed that in the late ontogeny the number of spontaneously active neurons was significantly decreased, the proportion of slowly firing neurons increased, the interspike intervals and intervals between spike groups became longer, the number of spikes in a group reduced. The ability of hippocampal neurons to acquire and reproduce the rhythm of the previous stimulation declined with age. No appropriate rhythms were found in neurons of very old animals. A nonspecific increase in neuronal baseline activity was observed in old rabbits after the stimulation. Deterioration of morphological structures of hippocampal neurons and glial cells may explain the impairment of mnestic processes in late ontogeny.     

The morphofunctional characteristics of the neurons in the sensorimotor cortex of old rabbits during the trace assimilation of rhythm]

Extracellular neuronal activity was recorded from 460 neurons from alert young (5-7 months), middle-aged (54-65 months) and old (66-85 months) rabbits. Trace rhythmic activity of sensorimotor cortical neurons was examined after long-lasting (10-20 min) rhythmic (0.5-2 Hz) electrocutaneous stimulation of the contralateral forelimb. Spectral analysis of spike activity showed age-related differences in capability of producing a rhythm of previous stimulation in spontaneous neuronal activity. In young animals propriate rhythmic fluctuations of firing rate appeared after the first or second sessions of stimulations (on the first experimental day), in middle-aged ones--after 2-4 sessions (on the second or third days); cortical neurons in old rabbits did not exhibit trace rhythmic activity. Significant morphological changes in glial and neuronal cells were observed in sensorimotor cortex of old rabbits. It is proposed that morphological deteriorations may be the reason of the impairement of trace processes during aging.     

Plastic changes in the spontaneous activity of pond snail neurons during rhythmic and associated intracellular electrostimulation

In experiments on spontaneously active neurones of the isolated CNS of pond snail, under contingent stimulation with selective auto-reinforcement of interpulse intervals longer than their mean background value, 70 per cent of neurones were capable of adaptive rearrangements of the initial firing frequency, leading to frequency minimization or maximization of influences applied to them. After control rhythmic stimulation, usually no substantial changes of spontaneous activity were observed. The detected phenomena of initial transformation of the spontaneous impulse activity are considered as a cellular analogue of the instrumental conditioned reflex.     

The role of GABA-ergic regulation in organizing spontaneous and evoked activity of the septal neurons

Effects of GABA, pentobarbital and picrotoxin upon spontaneous and evoked activity of neurones of the medial septal nucleus and the nucleus of the diagonal band (MS-DB) were investigated in the guinea pig septal slices. GABA and pentobarbital have similar effect upon all neurones, but the cells with a regular single spike and rhythmic burst activity of pacemaker type were less sensitive to their inhibitory influence. Picrotoxin affects neither frequency, nor pattern of activity. Electrical stimulation of the medial forebrain bundle evoked initial suppression of activity in majority of the neurones (74%); the remaining cells reacted mainly with an initial burst. GABA and pentobarbital increased the duration of the initial inhibition and revealed it in all cells with initial excitation in the control state. Picrotoxin did not influence this type of response, but revealed initial short-latency bursts in the cells with inhibitory effect in control state. The experiments show double nature of the effect of afferent stimulation controlling the activity of the MS-DB neurones. The mechanism of synchronization of the rhythmic activity in MS-DB, resulting in generation of the hippocampal theta-rhythm, is discussed.     

Spontaneous activity of hippocampal neurons and stimulation rhythm acquisition in young rabbits during learning: age features

Ontogenetic mechanisms of memory formation were studied using an experimental model of conditioned reflex to time, i.e., trace acquisition of a stimulation rhythm by hippocampal CA1 neurons of young (1-4 weeks old) and adult rabbits (5-6 months old). It was found that age-related development of learning ability includes several stages: complete absence of memory traces (6-7 days old), rapid acquisition without consolidation (8-14 days old), and formation of perfect memory (25-30 days old). Both specific and nonspecific changes in spontaneous activity of neurons were observed. Changes in the rate of discharges related to rhythmic stimulation were accompanied by changes in spontaneous activity. With the development of an animal, spike activity increased in parallel with improving of the functional properties of neurons, their structural organization, formation of the afferent contacts in the hippocampus completed after a period of three weeks from birth, and formation of metabolic processes, modulatory systems, and traffic function of hippocampal neurons. A capability for plastic reorganization is of great importance for adaptation mechanisms and conditioned behavior of a developing animal in accordance with structural maturation and development of the functional regulation of neuronal reactivity in the hippocampus.     

The excitability of neurons of the medial septal area in brain slices from hibernating and active Citellus undulatus susliks]

Spontaneous and evoked neuronal activity of the medical septum-diagonal band complex (MS-DB) has been investigated in slices from the brain of hibernating and active ground squirrels, as well as guinea pigs. In all experimental groups, the majority of the MS-DB neurones exhibited high regular of rhythmic burst spontaneous activity which persisted even after synaptic blockade in half of the neuronal population. Under the same conditions, the activity of the surrounding structures was completely suppressed. The density of the spontaneously active neurones in the slices, as well as the mean frequency of discharges in the MS-DB of hibernating ground squirrels, were significantly higher than in active ground squirrels and guinea pigs. Stimulation of the medial forebrain bundle evoked initial suppression of the activity in the majority of MS-DB units; in many of them, the suppression was followed by a burst discharge. Neurones with background rhythmic burst activity always reacted by resetting the spontaneous bursts. In total, 50-60% of the MS-DB neurones in active ground squirrels and guinea pigs reacted by post-inhibitory bursts, whereas in hibernating animals these responses were observed nearly in all neurones. Threshold values of the stimulating current were lower in hibernating animals; the intraburst density of spikes was increased.     

Neuronal correlates of changes in the defensive behavior of Helix lucorum L. during ontogeny

In experiments on the isolated nervous system, responses of the same command neurones of avoidance behaviour to electrical stimulation of the intestinal nerve were compared in adult snails (Helix pomatia) and in snails 1-20 days old. Dynamics of spike reactions of the command neurones to rhythmic nerve stimulation differed in adult and newborn snails. In the neurones of young snails, no sensitization, common in the adult animals, was observed. Study of excitatory input in the command neurones during rhythmic nerve stimulation suggests independence of habituation of synaptic input amplitude and spike response sensitization, because dynamics of habituation coincided in the young and adult snails while spike response underwent sensitization only in adult animals.     

Functional regulation of the neuronal activity of the rat hippocampus transplanted into the rabbit septum

Embryonal tissue of the rat hippocampus was grafted into dorsolateral septum of the rabbit after its disconnection from the hippocampus. Extracellular investigation of the grafted neurones was performed in chronic conditions 6 to 7 weeks later. The grafted neurones had some characteristics typical of the rat hippocampus (low spontaneous activity and presence of complex spikes, low-frequency rhythmic modulation--below 1 Hz, significant increase of activity level after physostigmine injection). Weak periodic theta-modulation, observed in spontaneous activity of some grafted neurones, became more stable and appeared in additional units after injection of physostigmine, under the influence of electrical stimulation of the septum and reticular formation and in response to sensory stimulation of the host animal. Its frequency was 4.5-6.0 Hz, as in the host septum. Microelectrode investigation for 5-10 days provoked lymphocyte infiltration of the grafts, which was not observed in the grafts not subjected to such treatment.     

Influence of certain stimulation parameters on the character of the cortical self-sustained after-discharge

The ECoG pattern of self-sustained after-discharges (SSADs) evoked by rhythmic electrical stimulation of the cerebral cortex is far from uniform. In acute experiments on male rats the authors studied the significance of the frequency, intensity and length of stimulation for the character of the resultant SSAD. In the first group (11 rats), a stimulation frequency of 8 Hz was used; the stimulation series, which lasted 10 and 20 s, always led to the formation of a SSAD composed of spike-and-wave rhythm right from the outset. Shortening the time of stimulation markedly reduced its effectiveness. In the second group (10 animals), stimulation with 50 Hz frequency often evoked a complex SSAD starting with desynchronization, which was followed by fast spike activity of increasing amplitude and only later by spike-and-wave rhythm or by polyspike-and-wave rhythm. Towards the end, serrated waves--i.e. graphoelements typical of SSADs evoked by electrical stimulation of limbic structures--often appeared in the SSAD. A higher stimulation intensity increased the incidence of this complex SSAD. In this group a minimum duration of stimulation was also essential (series of less than 2 s were not reliably effective). When this second type of SSAD ended, depression of ECoG activity was followed in 27% of the cases by a spontaneous recurrent seizure (RS). The ECoG character of these RS can be very variable. The two types of seizures evoked by slow and fast stimulation differ from each other not only in respect of their ECoG pattern (where the difference is probably due to more pronounced propagation to subcortical structures after faster stimulation), but also as regards the presumed mechanism of their onset.     

Investigation of the functional role of the septum

A spectral-correlation analysis was made of the EEG recorded from the motor and visual cortex, hippocampus, and septum (in some series of experiments, the lateral geniculate body and mesencephalic reticular formation also) of rabbits in the presence or absence (background) of sensory stimulation. To investigate the functional role of the septum as a pacemaker the method of "rhythm binding" by electrical stimulation of the septum (lateral and medial nuclei) was used. By electrical stimulation of the medial nucleus of the septum at a frequency of 4–30 Hz rhythm binding was successfully obtained in all regions studied. Maximal rhythm binding was observed in cortical potentials. It is postulated that cortical rhythmic activity is generated as a result of physiological interaction between cortex and septum.Institute of Higher Nervous Activity and Neurophysiology, Academy of Sciences of the USSR, Moscow. Translated from Neirofiziologiya, Vol. 8, No. 3, pp. 267–275, May–June, 1976.     

Frequency modulation of theta volleys of septal neurons during rhythmic oligosynaptic stimulation in the rabbit

Activity of the neurones with stable theta-bursts was recorded extracellularly in intact and hippocampectomized septum of unanaesthetized chronic rabbits during low-frequency (3-17 Hz) stimulation of horizontal limb of the diagonal band or the lateral septal nucleus. Gradual entrainment and phase-locking of the spontaneous theta-cycles occurred. Two types of entrainment were observed: "entrainment by pause", where interburst interval was reset by the stimuli; and "entrainment by burst", where bursts were time-locked to the stimuli. Such reorganization of the spontaneous bursts occurred in a narrow frequency range of stimulation (from 4 Hz up to 9-12 Hz), with the best resonance following in the range of "basic" theta frequencies of the awake rabbit (5-6 Hz). With stimulation beyond the theta-range three phenomena occurred: shift of the burst frequencies to higher or lower harmonics of stimulation frequencies; complex interactions of basic background frequency with the rhythm of stimulation ("beating"); escape from the influence of the stimuli with return to background theta-burst frequency.     

The morphochemical characteristics and plastic restructurings of the hippocampal neurons after rhythmic stimulation of an extremity in old rabbits]

The rhythmic activity of CA1 hippocampal neurons was studied after the rhythmic (1-2 Hz) electrocutaneous forelimb stimulation (10-20 min) of 6-84-months-old rabbits. The spectral analysis of neuronal activity revealed the age-dependent decrease in ability to reproduce the rhythm of stimulation. The cytochemical data showed that the protein synthesis in the neurons under study also declined with age.     

Regulation of the plastic properties of an electro-excitable neuronal membrane by serotonin

The action of serotonin on plastic properties of electroexcitable membrane was studied in Helix lucorum parietal ganglia on neurones of two types: habituating (HC) and nonhabituating (NHC) to rhythmic intracellular stimulation by impulses of depolarizing current. Serotonin produced an effect of facilitation on HC (increase of responses to stimulation against the background of depolarization and rise of input resistance of the cell). Besides, serotonin completely blocked the ability of these cells to habituate to rhythmic stimulation. The obtained data testify that such action of serotonin may be based on suppression by it of C-dependent K-conductivity. Serotonin suppresses responses of NHC to stimulation and contributes to their habituation to rhythmic stimulation. Such action is due to serotonin suppression of Ca-conductivity, and, consequently, to elimination of the mechanism of action potential generation.     

The effect of a vasopressin analog on the reaction of the command neurons in the defensive behavior of the edible snail during nerve stimulation

On the level of snail command neurones of the defensive behaviour an increase was revealed of the amplitude of summary EPSP recorded in command neurones in response to nerve stimulation, an increase of probability of appearance of action potential in the reaction and, under certain conditions, a significant decrease of habituation speed at rhythmic (0.1 Hz) nerve stimulation against the background of peptide. The latter effect was found during comparison of groups of neurones--control neurones and those to which the peptide was presented before the first series of stimulation in the test, i. e. without preliminary elaboration of habituation. The decrease of the speed of habituation concerned both the amplitude of summary EPSP and the probability of action potential appearance in the reaction. All these changes against the background of vasopressin analogue may be the basis of the increase of spike reactions of command neurones of the defensive behaviour and thus the basis of the initiation or the increase of behavioural defensive reactions. The obtained effects were not protracted and took place only in the presence of the peptide in the extracellular medium.     

The Lateral Hypothalamic Area: Peculiarities of Aging and the Effect of Chronic Electrical Stimulation on the Lifespan in Rats

Age-related morphological and functional changes in the lateral hypothalamic area (LHA) were studied in experiments on young adult (6-8 months) and old (26-28 months) male Wistar rats. It was found that during aging the neuronal density in the LHA decreased, and significant qualitative destructive and dystrophic changes in the neuronal population developed. The background impulse activity of LHA neuronal units, the mass background electrical activity recorded from this structure, and the Na⁺, K⁺-ATPase activity decreased during aging. In old rats, the rate of LHA self-stimulation was lower, and the range of reinforcing current amplitudes, which provided self-stimulation intensity close to the maximum, was narrower than in adult animals. Chronic electrical LHA stimulation in old rats ensured an increase in the lifespan and maximum life expectancy in these animals. In addition, the lifespan positively correlated with the duration of LHA stimulation. It is concluded that lowering of the functional activity of the LHA neural systems is one of the substantial aspects of the aging process, and activation of this structure in old animals by its chronic electrical stimulation can exert a geroprotective effect.     

Electrophysiological characteristics of reticulospinal neurones in relation to the conduction velocity of their axons

Activity was recorded intracellularly from the bodies of 87 reticulospinal neurones in the cat's gigantocellular nucleus, whose axons had a conduction velocity of 18-148 m.s-1. Slow-conducting neurones (18-45 m.s-1, 23%) were characterized by a wider action potential, higher input resistance (3.8-7.0 M omega) and a lower rheobase (1.0-1.7 nA). They were also very sensitive to changes in membrane polarity and generated regular rhythmic activity. Fast-conducting neurons (45-148 m.s-1) were characterized by a short action potential, low input resistance (0.7-2.9 M omega) and a higher rheobase (1.5-5.2 nA). When depolarizing current pulses were applied, they generated responses with action potentials with a high frequency, especially in the initial phase of depolarization, but their thresholds for the initiation of activity and steady firing were higher than in the case of slow neurones. Slow reticulospinal neurones always responded to stimulation of the spinal funiculi (mainly the dorsal funiculus) by a characteristic large postsynaptic potential on which large numbers of spike potentials were superimposed and which did not occur in fast neurones. The differences observed in membrane properties and in the character of generation of action potentials draw attention to the phasic character of fast, and the tonic character of slow, reticulospinal neurones.     

The neuronal organization of a focus of conditioned excitation in the cat sensory-motor cortex]

The activity of single units in the focus of conditioned excitation was studied during defensive conditioning to direct electrical stimulation of the cat sensorimotor cortex. Reorganizations of spike activity set in during the period of reflex elaboration, were manifest in the increased number of excited neurones and those which respond both to the conditioned and unconditioned stimuli. In the course of elaboration, the inhibitory phase of unit responses to direct electrical stimulation of the sensorimotor cortex was reduced, while the frequency of background unit spike activity was enhanced. Acute extinction of the reflex restored the initial duration of the inhibitory phase and reduced the frequency of the background activity.     

The action of L-DOPA on the structure of spontaneous motor activity in rat pups

In experiments on 2-3-, 7-8-, 10- and 16-day old rat pups, basic age differences have been observed in the effect of a precursor of catecholamine mediator, i.e. L-DOPA on the activity on the spinal and brain mechanisms of autogenic periodic motor excitation. Strong stimulation of the spinal motor rhythm was observed during the first week. At this period, supraspinal rhythm becomes even less evident. On further development, the effect is an opposite one. In 10- and 16-day rat pups, at the background of total inhibition of the spontaneous activity, administration of L-DOPA significantly increases the activity of supraspinal generator of the motor rhythm. The data obtained reveal ontogenetic changes in regulatory mechanisms of autogenic motor activity.     

The modelling of theta rhythm regulation by an increasing afferent inflow in septal slices in vitro

The aim of the work was the modelling in vitro of the condition of increased afferent inflow, which in the intact septum results in an increase of population of theta-bursting units, their synchronization and shift to a higher frequency of the bursts, with corresponding changes in the hippocampal electrical activity. Neuronal activity was recorded extracellularly in the medial septal nucleus and vertical limb of the nucleus of diagonal band (MS-DB) in guinea pig septal slices. Electrical stimulation in the medial part of horizontal limb of DB evokes initial period of suppression of spontaneous activity in 85% of the neurones. This low-threshold, rapid inhibition has variable duration (20-280 ms) in different units at low intensities of the stimulating current. With increased intensities of stimulation this inhibitory phase in majority of units is gradually or by steps shortened, though in some units with initial short inhibition it is not changed. As a result the variability of initial inhibitory period between units is decreased and centered around 30-60 ms. Many units with single-spike background activity developed postinhibitory burst responses at various levels of stimulating current. The spontaneously bursting MS-DB units always responded by resetting of their background bursts. In total 58% of all recorded neurones generated evoked bursts under condition of increased afferent inflow.