Modifications of neuronal activity in the rat hypothalamic supraoptic nucleus after long-lasting vibrational stimulation

We analyzed the background impulse activity (BIA) generated by neurons of the rat hypothalamic supraoptic nucleus in the norm and under conditions of long-lasting vibrational stimulation (exposure 5, 10, or 15 days). Distributions of neurons by the level of regularity, dynamics of discharge trains, form of histograms of interspike intervals (ISIs), as well as distributions of neurons by the BIA frequency ranges, were studied. We also calculated the mean frequency of impulsation of the neurons under study and the coefficient of variation of ISIs. After vibrational influences, we found modifications of both the internal structure of the recorded spike trains and the mean frequency of impulsation within the entire studied group and different frequency subgroups. Neirofiziologiya/Neurophysiology, Vol. 38, No. 3, pp. 224–230, May–June, 2006.     

Protective Effects of Hypothalamic Proline-Rich Peptide and Cobra Venom Naja Naja Oxiana on Dynamics of Vestibular Compensation Following Unilateral Labyrinthectomy

We tested the action of proline-rich peptide (PRP-1) and cobra venom Naja Naja Oxiana (NOX) on Deiters’ nucleus neurons at 3rd, 15th and 35th days after unilateral labyrinthectomy (UL). Early and late tetanic, post-tetanic potentiation and depression of Deiters’neurons to bilateral high frequency stimulation of hypothalamic supraoptic and paraventricualar nuclei was studied. The analysis of spike activity was carried out by mean of on-line selection and special program. The complex averaged peri-event time and frequency histograms shows the increase of inhibitory and excitatory reactions of Deiters’ neurons at early stage of vestibular compensation following PRP-1 and NOX injection, reaching the norm at the end of tests. In histochemical study the changes in Ca²⁺-dependent acidic phosphatase (AP) activity in neurons was discovered. It was shown that in UL animals the total disappearance or delay of decolorizing of Deiters’ neurons lead to neurodegenerative pattern as cellular “shade”. AP activity after UL and PRP-1 injection exerts more effective recovery of neurons in comparison with events, observed after the administration of NOX. The data of this study indicate that PRP-1 and NOX are protectors, which may successfully recover the disturbed vestibular functions.     

Effects of the blockade of the system of opioid peptides on changes in emotional/behavioral reactions of rats induced by the action of extrahigh-frequency electromagnetic radiation in the norm and under conditions of hypokinetic stress

We studied the effects of pharmacological blockade (by injections of naloxone) of the system of opioid peptides on changes in emotional/behavioral reactions of rats in the open-field test. These changes were caused by the isolated action of low-intensity electromagnetic radiation (EMR) of extrahigh frequency (EHF) and its combination with experimentally induced hypokinetic stress. We conclude that one of the mechanisms of physiological effects of low-intensity EHF EMR is an increase in the functional activity of the system of regulatory opioid peptides; this results in adaptive modifications of the emotional/behavioral reactions under new conditions of the open-field test and provide an anti-stress effect under conditions of hypokinetic stress. Neirofiziologiya/Neurophysiology, Vol. 38, No. 1, pp. 52–60, January–February, 2006.     

Roles of different neurochemical systems in mechanisms underlying the antinociceptive effect of extrahigh-frequency electromagnetic radiation

We studied the effect of low-intensity extrahigh-frequency (EHF) electromagnetic radiation (EMR) on the duration of a pain behavioral reaction in rats under conditions of experimental induction of tonic pain (formalin test). The antinociceptive effect of EHF irradiation was modulated by suppression of the activity of a few neurochemical systems resulting from the blockade of receptors of opioid peptides, α-and β-adrenoreceptors, receptors of dopamine and melatonin, as well as from inhibition of serotonin synthesis. We demonstrated that all the respective neurochemical systems are to a certain extent involved in the mechanisms underlying the analgesic action of EHF EMR. Within an early phase of pain stress, functioning of the opioidergic and noradrenergic systems and the effects of melatonin play leading roles, while the activity of the serotonergic system plays such a role within the second (tonic) phase. Neirofiziologiya/Neurophysiology, Vol. 39, No. 2, pp. 165–173, March–April, 2007.     

Activation of neurons of zone A5 of the rat brain upon hypoxic and thermonociceptive stimulation and switching off of the central respiratory generator

We recorded spike activity of noradrenergic neurons of zone A5 (n = 89) in the brain of anesthetized rats under conditions of hypoxic stimulation (breathing with pure N₂, 10 sec), thermonociceptive stimulation (tail-flick test), and reversible hypothermal blocking of the central respiratory activity. Hypoxic stimulation of peripheral O₂-sensitive chemoreceptors considerably increased the discharge frequency in all the examined neurons and induced tachypnea and a hypotensive reaction. Sixty-nine (77.5%) neurons of the studied group were tested using nociceptive stimulation (thermal stimulation of the tail); such stimulation resulted in a multifold increase in their discharge frequency. This was accompanied by tachypnea and a hypertensive response. Thus, we first demonstrated the role of nociception in the control of activity of noradrenergic neurons in zone A5 and the role of nociceptive afferent signals in the modulation of functions of the respiratory and cardiovascular systems mediated by neurons of the above zone. Under conditions of blocking of the central respiratory activity, we examined 36 (40.4%) neurons of zone A5 and first observed the effect of strong activation of a significant proportion of these cells upon switching off of respiration. This fact shows that there is an activating “respiratory” drive on neurons of zone A5 (probably, from the side of an expiratory neuronal population of the respiratory center) and allows us to hypothesize on the genesis of “respiratory” modulation of these cells. The activity of 16 (18.0%) cells was recorded under conditions of consecutive applications of the above stimuli; all the neurons were activated by the respective afferent influences. The simultaneously induced effects of hypoxic and nociceptive stimulations on the activity of neurons of zone A5 were additive. Thus, we first obtained proofs in favor of the multimodality of noradrenergic neurons of the above zone. This feature is a significant factor providing integrative interaction between the respiratory and cardiovascular systems and the system of nociception. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 305–313, July–August, 2006.     

Presumed mechanisms of a long-term increase in the intrinsic excitability of cerebellar granule cells: A model study

Persistent use-dependent changes in the intrinsic neuronal excitability determine the long-term dynamics of the activity of these neurons. In synergy with the long-lasting modification of synaptic transmission, such changes in the excitability presumably contribute to the formation of a memory trace in the brain. Nevertheless, neither particular transmembrane ion conductances implicated in the intrinsic plasticity nor the mechanisms of regulation of such conductances have been identified in most neurons where this plasticity was observed. In our model study, we tried to determine those membrane conductances in cerebellar granule cells (GrCs) whose changes can result in a persistent increase in the input resistance and a decrease in the spike threshold observed after high-frequency stimulation of presynaptic neurons. For this purpose, published experimental results were simulated with the use of a slightly modified model of the electroresponsiveness of rat cerebellar GrCs. It was concluded that experimentally observed changes in the input resistance of the neuron, in the minimum current step needed to fire action potentials (APs), in the spike threshold, in the average spike frequency, and in the delay of the first spike may be caused only by changes in the background voltage-independent potassium conductance and persistent sodium conductance. Hyperpolarization-directed shifts in the activation and inactivation curves of fast sodium channels are also possible. The observed changes in the intrinsic excitability evoke the shift in the peak of the frequency-response curve in such a manner that it becomes close to the frequency of oscillations recorded in the cerebellar granular layer during realization of voluntary movements. Neirofiziologiya/Neurophysiology, Vol. 38, No. 2, pp. 119–130, March–April, 2006.     

Evoked Electrical Activity and Immunocytochemical Peculiarities of Cultured Excitatory and Inhibitory Neurons of the Rat Hippocampus

Experiments were carried out on cultured hippocampal neurons using a patch-clamp technique in the whole-cell configuration. We studied the characteristics of regular series of action potentials (APs), which were generated with a low frequency by inhibitory and excitatory interneurons after their direct stimulation with long-lasting (500 msec) current pulses. Nearly all parameters of the evoked impulse activity (except the frequency of generation and duration of APs) in excitatory and inhibitory neurons were significantly different. According to immunocytochemical analysis, Kv1.2- and Kv4.2-type potassium channels were expressed in the membrane of excitatory neurons (granular cells), and somatostatin was present in all these cells. As to inhibitory interneurons, only a part of such cells (large units) demonstrated immunopositivity with respect to somatostatin. In inhibitory neurons, only Kv1.2-type potassium channels were expressed. Therefore, mechanisms responsible for the ability of hippocampal interneurons to generate impulse activity under conditions of direct stimulation (in our experiments, regular low-frequency series of APs) in inhibitory and excitatory neurons are rather dissimilar. Neirofiziologiya/Neurophysiology, Vol. 37, No. 3, pp. 207–216, May–June, 2005.     

Antinociceptive effects of low-intensity extrahigh-frequency electromagnetic radiation

We studied the effect of low-intensity extrahigh-frequency (EHF) electromagnetic radiation (EMR) on changes of behavior phenomena in rats observed under conditions of experimentally induced tonic somatic, visceral, and acute thermal pain. Preliminary irradiation of the animals with EHF EMR was found to exert clear antinociceptive effects. Decreases in the intensity of pain reactions were observed under conditions of both single and repeated irradiation sessions. Neirofiziologiya/Neurophysiology, Vol. 38, No. 4, pp. 331–341, July–August, 2006.     

Pattern of response in neurosecretory cells of the rat hypothalamic supraoptic nucleus to subiculum stimulation under water deprivation

The effects of water deprivation were investigated in the pattern of response produced by subiculum stimulation in antidromically identified hypothalamic supraoptic neurosecretory cells of lactating rats. In dehydrated animals as compared with the controls, the percentage of neurons responding to subiculum stimulation with an inhibitory action (blockade of antidromic action potential) remained unchanged, although the proportion of differing inhibitory response did alter: numbers of cells with gradually developing inhibitory response increased significantly and fewer cells showed transitory development of inhibition. Inhibitory response emerging as depression of background spike activity showed a quantitative increase, moreover. Plasticity was found to be one distinguishing feature of afferent input from the subiculum to supraoptic nucleus neurosecretory cells and, in particular, a capacity for reorganization under water deprivation.A. A. Ukhtomskii Institute of Physiology, State University, Leningrad. Translated from Neirofiziologiya, Vol. 22, No. 2, pp. 243–249, March–April, 1990.     

Antidromic indentification of hypothalamic neurosecretory cells in rats

Characteristics of antidromic action potentials of neurons of the paraventricular and supraoptic nuclei of the rat hypothalamus were studied during stimulation of the hypothalamo-hypophyseal tract by stimuli of varied amplitude and frequency. Step-like changes were found in spike latency in response to an increase in strength (up to 1.5–2.5 thresholds) or frequency (over 100 Hz) of stimulation, as well as cases with variation of the degree of division of the peak into A and B components. Injection of leu-enkephalin analog into the third ventricle or intravenous injection of NaCl solution (1 M) caused reversible changes in the level of excitability of antidromically activated neurons: leu-enkephalin mainly increased the latent period and threshold of action potential generation and reduced the reproducible frequency of stimulation to 10 Hz, whereas NaCl had the opposite effect. The results indicate that when the adopted criteria of antidromic identification of neurosecretory cells are used the level of their excitability must be taken into account.A. A. Ukhtomskii Physiological Research Institute, A. A. Zhdanov Leningrad State University. Translated from Neirofiziologiya, Vol. 14, No. 6, pp. 585–591, November–December, 1982.     

Accommodation properties of isolated hippocampal neurons under conditions of an experimental model of epilepsy

A pilocarpine/lithium model of status epilepticus is an effective tool allowing one to study the principles of development of temporal epilepsy. It is believed that, in addition to the corresponding modifications of the efficacy of synaptic transmission, changes in the endogenous properties of neuronal activity can promote repetitive epileptiform activity. We measured the accommodation parameters of spike generation by isolated neurons of the CA1 hippocampal area obtained from 14-day-old rats 2 or 24 h after they had been subjected to an epileptization procedure, as well as from control rats of the same age. The spike activity of the neurons was initiated by their depolarization with a long-lasting stimulus in a current-clamp mode under conditions of perforated patch clamp. We found that the initial phase of accommodation manifested as a rapid increase in interspike intervals immediately after application of the depolarizing stimulus became significantly shorter in rats 24 h after epileptization; at the same time, the characteristics of the late phase of accommodation underwent no changes. In addition, the mean number of generated action potentials dropped. Such changes were not found in neurons of rats 2 h after epileptization. It is hypothesized that the above effect is compensatory and not injuring; it can develop because of prolonged abnormal activation of neurons in the course of epileptic attacks. Neirofiziologiya/Neurophysiology, Vol. 38, No. 3, pp. 211–218, May–June, 2006.     

Dynamics of the background impulse activity of neurons of the lateral vestibular nucleus in the norm and under vibrational influence

The background impulse activity (BIA) generated by neurons of the right lateral vestibular nucleus (LVN) of rats in the norm and under conditions of long-lasting general vibrational stimulation was subjected to computer analysis. Statistically significant changes in intragroup values of the mean BIA frequency were observed after 5 and 10 days with 2-h-long sessions of vibrational stimulation. Significant shifts in the distributions of LVN neurons by the level of regularity and dynamic types of BIA were observed 10 and 15 days with vibrational influences. Trends toward return of the intragroup mean value of the BIA frequency to the initial level were noticeable at the end of the stimulation period (15 days). Neirofiziologiya/Neurophysiology, Vol. 37, Nos. 5/6, pp. 424–431, September–December, 2005.     

Activity of neurons of the cerebral A5 zone of rat induced by adequate stimulation of muscle afferents: On the control of arterial pressure and respiration during muscle activity

In experiments on 24 anesthetized rats with preserved spontaneous respiration, we first recorded the volley impulse activity of neurons (n = 30) in the brainstem A5 zone, which was induced by periodical stretchings of the forelimb flexors and hindlimb extensors. The frequency of action potentials in such volleys was, on average, 99.7 ± 19.6 sec⁻¹. In the course of this kinesthetic stimulation, along with the activation of “proprioceptive” neurons of the A5 zone, we observed transitory drops in the arterial pressure and increases first recorded the activity of baroceptive neurons in subpial parts of the A5 zone (n = 4); the frequency of their background impulsation was, on average, 25.1 ± 0.8 sec⁻¹. This activity in all cases was transitorily suppressed both upon increases of the blood pressure caused by constriction of the carotid arteries or nociceptive tail stimulation, as well as upon stretching of skeletal muscles. Therefore, we first obtained direct proof that neuronal systems of the A5 zone are involved in integration of visceral and somatic proprioceptive afferent influences. We hypothesize that the physiological role of this mechanism of integration of somatic and visceral information at the level of the A5 zone is directed toward lowering of the arterial pressure and intensification of respiration within the period of intensified motor activity. This mechanism is based on the interaction between “proprioceptive,” baroceptive, and, perhaps, multiceptive neurons within the A5 zone. Neirofiziologiya/Neurophysiology, Vol. 39, No. 6, pp. 443–452, November–December, 2007.     

Background impulse activity of neurons of the fastigial cerebellar nucleus of intact and labyrinthectomized rats under conditions of vibration

In acute experiments on nembutal-anesthetized (40 mg/kg, i.p.) albino rats, we recorded extracellularly and analyzed the background impulse activity (BIA) of neurons of the fastigial nucleus of the cerebellum. Experiments were carried out on intact and labyrinthectomized rats in the norm and after long-lasting (up to 15 days) influence of general vertical vibration (60 Hz, 0.4 mm, 2-h-long everyday sessions). Distributions of the neurons according to the level of regularity of BIA, dynamics of spike trains, pattern of histograms of interspike intervals (ISIs), and different frequency ranges of BIA were plotted; the mean frequency of this activity and the coefficient of variation of ISIs were also calculated. Possible mechanisms of the effects of long-lasting vibration of different durations on the BIA generated by neurons of the fastigial cerebellar nucleus in intact animals and after switching off of labyrinth afferent inputs are discussed. Neirofiziologiya/Neurophysiology, Vol. 38, No. 1, pp. 32–39, January–February, 2006.     

Projections from the ventral subiculum to supraoptical hypothalamic region neurons not responding to stimulation of the hypophyseal pedunculus

Effects of subiculum stimulation on spike activity of neurons localized in the supraoptical nucleus (SON) and perinuclear region were studied in experiments on rats; special attention was paid to neurons that did not respond to stimulation of the hypophyseal pedunculus. With rare exception, the SON cells did not respond to subiculum stimulation; 47% of neurons in the perinuclear region were activated after subiculum stimulation, whereas in 15% the frequency of spike activity decreased. Some neurons were found in the perinuclear region that responded to subiculum stimulation by antidromic spike generation.Organization of the studied afferent input to neurons of the supraoptical region and probability of interconnections between investigated structures are discussed.Neirofiziologiya/Neurophysiology, Vol. 25, No. 4, pp. 253–257, July–August, 1993.     

Background neuronal activity in thenucleus supraopticus and its modifications under the influence of parathyroid hormone

In experiments on anesthetized cats, we found that i. v. injection of 5.0 U/kg of parathyroid hormone (PTH) results in modifications of the statistical parameters of the neuronal impulse activity in thenucleus supraopticus (SO) of the hypothalamus. Sliding frequency graphs, histograms of interspike intervals, autocorrelograms, and serial correlation coefficients were plotted and calculated before and after PTH injections; their comparison demonstrates that the hormone significantly modulates the temporal organization of spike trains generated by the neurons of this nucleus. We observed that PTH mostly activated SO neurons and diminished the level of spike grouping in their activity. The effect of PTH to a certain level depended on the initial frequency of background activity: an increase in the spiking frequency was typical of primarily dominating “low-frequency” neurons, while “high-frequency” units were mostly inhibited. The possible mechanisms of the observed modifications are discussed.     

Pheromone-evoked potentials and oscillations in the antennal lobes of the sphinx moth Manduca sexta

Using intra- and extracellular recording methods, we studied the activity of pheromone-responsive projection neurons in the antennal lobe of the moth Manduca sexta. Intracellularly recorded responses of neurons to antennal stimulation with the pheromone blend characteristically included both inhibitory and excitatory stages of various strengths. To observe the activity of larger groups of neurons, we recorded responses extracellularly in the macroglomerular complex of the antennal lobe. The macroglomerular complex is part of a specialized olfactory subsystem and the site of first-order central processing of sex-pheromonal information. Odors such as the pheromone blend and host-plant (tobacco) volatiles gave rise to evoked potentials that were reproducible upon repeated antennal stimulation. Evoked potentials showed overriding high-frequency oscillations when the antenna was stimulated with the pheromone blend or with either one of the two key pheromone components. The frequency of the oscillations was in the range of 30–50 Hz. Amplitude and frequency of the oscillations varied during the response to pheromonal stimulation. Recording intracellular and extracellular activity simultaneously revealed phase-locking of action potentials to potential oscillations. The results suggest that the activity of neurons of the macroglomerular complex was temporally synchronized, potentially to strengthen the pheromone signal and to improve olfactory perception. Accepted: 19 December 1997     

Neuronal electrical activity in the epileptic focus produced by electrical stimulation in an isolated cortical slab

Characteristics of neuronal activity in an isolated cortical slab were investigated during the onset of seizure spikes induced by frequent and powerful stimulation of the slab during experiments on unanesthetized immobilized cats. A high degree of coordination between the activity of cellular elements was found in the focus of epileptiform activity studied: convulsive shifts in membrane potential exactly corresponding to electrocorticograms of convulsive activity waves were observed in all neurons studied using intracellular techniques. No action potentials occurred in the soma of any of these neurons, moreover. Bursting spike discharges were recorded from neurons of the isolated slab at the same time. Findings from extra- and intracellular recordings of activity in the same neurons showed that action potentials are generated during convulsive activity at certain trigger zones remote from the cell in question without involving the soma, from which convulsive shifts in membrane potentials were recorded simultaneously. Mechanisms possibly underlying the generation of spike activity in neurons of the isolated slab undergoing development of generalized convulsive state are discussed.I. I. Mechnikov State University, Odessa. Translated from Neirofiziologiya, Vol. 20, No. 3, pp. 357–365, May–June, 1988.     

Rhythmic aftereffects in the osmotic stimulation-induced spike activity of thermosensitive neurons of the preoptic region

Acute experiments on cats showed that mild shifts in osmotic homeostasis (within physiological limits) result in modifications of the spike activity in a significant share of thermosensitive neurons of the Preoptic region (RPO); in particular, rhythmic aftereffects (RAE) are induced in these units. The neurons were identified as thermosensitive cells according to their responses to local heating/cooling (±7°C) of the pad surface of the contralateral forelimb. Osmotic stimulation was performed by infusions of 0.1–0.3 ml of 3.0 or 0.2% NaCl solutions in thea. carotis communis dextra. The RAE phenomenon more frequently developed in thermosensitive neurons after infusions of the hyportonic solution (13/34) than after hypotonic infusions (6/34), while in non-thermosensitive neurons the situation was reverse: hypotonic infusions induced RAE more frequently. Certain specificities were also observed in localization of the thermosensitive RPO neurons, in which osmotic stimulation-induced RAE was observed. The mechanisms of such induction and possible functional role of spike grouping in the activity of thermosensitive neurons are discussed.     

Neuronal background of activation of estivated snails,with special attention to the monoaminergic system: a biochemical,physiological, and neuroanatomical study

Osmotic stimulation activates both estivated and inactivated specimens of Helix pomatia and increases their central arousal. High-pressure liquid chromatography has shown that, during activation, the level of both serotonin and dopamine decreases in the central nervous system (CNS) but increases in the foot and heart, organs that are involved in the eversion of the body. In isolated CNS from activated animals, the firing frequency of the heart-modulator serotonergic (RPas) neurons is significantly higher than that in the CNS of estivated or inactivated animals. These neurons innervate both the heart and the anterior aorta. In semi-intact preparations, distilled water (an osmotic stimulus) applied to the mantle collar increases their firing frequency, whereas tactile stimulation evokes their inhibition. Extracellularly applied monoamines mimic the effect of peripheral stimuli: serotonin (0.1–10 μM) increases the activity of the RPas neurons, whereas dopamine (0.1–10 μM) inhibits their activity. Tyrosine-hydroxylase immunocytochemistry and retrograde neurobiotin tracing have revealed similar bipolar receptor cells in the mantle collar and tail, organs that are exposed to environmental stimuli in estivated animals. Serotonin immunocytochemistry carried out on the same tissues does not visualize receptor cells but labels a dense network of fibers that appear to innervate neurobiotin-labeled receptor cells. The combination of neurobiotin-labeling of RPas neurons and immunolabeling suggests that RPas neurons receive direct dopaminergic inputs from receptor cells and serotonergic inputs from central serotonergic neurons, indicating that central serotonergic neurons are interconnected. Thus, the RPas neurons may belong to neuronal elements of the arousal system. This work was supported by Hungarian OTKA grants T037389, T046580, T037505, and K63451.