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.     

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.     

Structure of Neuronal Impulse Trains of the Rat Inferior Olive under Conditions of Long-Lasting Vibrational Influence

In acute experiments on albino rats anesthetized with Nembutal (40 mg/kg, i.p.), we recorded the background impulse activity (BIA) generated by neurons of the inferior olive in the norm and after 5-, 10-, and 15-daylong vibrational influence (60 Hz, 2 h, daily). We characterized the distributions of neurons according to the regularity of impulse successions, their dynamics, and pattern of histograms of interspike intervals (ISIs); we also calculated the mean frequency of impulsation and the coefficient of variation of ISIs. It was demonstrated that the most significant shifts of the characteristics of BIA generated by neurons of the inferior olive were formed within the first 10 days of the vibrational influence. These shifts were observed mainly in the mean discharge frequency (increased within the initial period) and, to a lesser extent, in the intrinsic structure of impulse trains. Such shifts in the background activity of the inferior olive caused by long-lasting vibrational influence result, perhaps, from intensification of the influences of excitatory cerebellar/mesodiencephalic inputs to olivary neurons within the early periods of action of the above factor and prevalence of GABAergic influences within the later periods. It seems possible that, under such conditions, the characteristics of electrical synapses of the olivary neurons are also subjected to modification. Neirofiziologiya/Neurophysiology, Vol. 40, No. 4, pp. 340–347, July–August, 2008.     

Background impulse activity of neurons of the fastigial nucleus in the rat cerebellum

Background impulse activity (BIA) of neuronal elements of the fastigial nucleus (FN) of rat cerebellum were investigated for the first time with the aid of various methods of statistical analysis. A clear predominance of stationary impulse flows (IFs) was discovered, along with irregularities in such flows, variously expressed and including a significant number of realizations of a regular component of impulse activity. Nonstationary IFs constituted a special variety of BIA; they were found in 15% of the total number of neurons investigated. Serial correlation analysis of the durations of interspike intervals (ISIs), both of stationary and nonstationary IFs, allowed us to identify six main varieties of ISI dynamics in the BIA of neurons of the fastigial nucleus. The patterns of recorded IFs and variations in IFs can serve as an adequate indices of the state of cellular activity during intracellular recording from cells of the central nervous system.L. A. Orbeli Institute of Physiology, Armenian Academy of Sciences, Yerevan. Translated from Neirofiziologiya, Vol. 23, No. 4, pp. 441–450, July–August, 1991.     

Comparative analysis of spontaneous unit activity of the cerebellum fastigial nucleus' neurons in different periods of vibration influence

In conditions of acute experiment on white rats anaesthetized with Nembutal (40 mg/kg, interperitonially) recording and analysis of spontaneous impulse activity of the fastigial nucleus' neurons in norm and after 5, 10 and 15 days of vibration influence on the organism were carried out. Distribution of the neurons was evaluated by the dynamics of neuronal current flow and the modality of the interspike interval hystograms, as well as the statistical parameters: the average discharge frequency and the coefficient of the interspike interval variation. It is shown that more significant changes in neuronal activity of fastigial nucleus cells are formed during the first 10 days of vibration influence. On the 15th day, there was a tendency towards return to control levels of the parameters under study.     

Background activity of neurons of the supraoptic hypothalamic nucleus in rats under conditions of vibrational stimulation and electromagnetic extrahigh-frequency irradiation

We analyzed background impulse activity of neurons of the supraoptic nucleus of the rat hypothalamus in the course of 15-day-long isolated action of generalized vibrational stimulation and combination of such stimulation with irradiation of the animal’s head with low-intensity extrahigh-frequency (EHF, millimeter-range) electromagmetic waves. The distributions of the neurons by the level of regularity and dynamics of spike trains, separate frequency ranges of impulsation, and pattern of interspike interval (ISI) histograms were estimated. We also calculated the mean frequency of discharges and coefficient of variation of ISIs. A trend toward decreases in the deviations of some parameters of neuronal spike activity generated by supraoptic neurons, which were evident within early time intervals of isolated action of vibration (5 to 10 days), was observed under the influence of EHF electromagnetic irradiation; thus, the latter factor probably exerts a sedative effect. Neirofiziologiya/Neurophysiology, Vol. 39, No. 6, pp. 433–442, November–December, 2007.     

Effect of Long-Lasting Vibration on the Impulse Activity of Neurons of the Inferior Vestibular Nucleus

We analyzed the impulse background activity (BA) of neurons of the inferior vestibular nucleus (IVN) of rats during exposure to long-lasting vibration (daily 2-h-long sessions). It was demonstrated that 5 days after the beginning of vibration stimulation, practically all main characteristics of the BA of IVN neurons changed significantly. In the studied neuronal group, 10 days after the vibration onset we observed an increase in the mean frequency of the BA and shifts in many statistical parameters of the BA, while after 15 days of vibration only significant modifications of dynamic characteristics of the BA of IVN neurons were manifested.Neirofiziologiya/Neurophysiology, Vol. 37, No. 1, pp. 32–38, January–February, 2005.     

Modulation of neuronal impulse activity of the anterior hypothalamus as a functional basis of the mechanisms underlying hypothalamic control

We examined the neuronal activity of hypothalamic neurons in acute experiments on cats under ketamine anesthesia. Using glass microelectrodes, we extracellularly recorded the impulse activity (IA) of neurons of the anterior hypothalamus in the absence of controlled influences (background IA, BIA) and after stimulation of evolutionary heterogeneous zones of the brain cortex projecting to the hypothalamus (hippocampal CA3 area, pyriform, cingular, and proreal gyri). Electrical 5-sec-long stimuli were applied with frequencies of 12, 30, or 100 sec⁻¹. In another experimental series, we recorded changes in the IA of hypothalamic neurons induced by visceral stimuli (heating or cooling by 7°C of the foot pad, cooling of the body of the animal, and infusions of 5% glucose, 0.2% NaCl, 3.0% NaCl, or phenylephrine in the carotid artery), modeling in such a way shifts of the constants of homeostasis within physiological limits. We also compared the parameters of neuronal BIA and stimulation-influenced IA in equal epochs of the analysis and classified the types of BIA. About 50% of the cells of the total studied sampling of hypothalamic neurons responded by a considerable modulation of their BIA with a significant change in the frequency in the course of and after stimulations of the above-mentioned modalities. In some neurons after cortical or visceral stimulation, a significant transformation of the temporal structure of the IA with no changes in the mean frequency occurred. We hypothesize that stimulation-induced transformation of the IA pattern with preservation of the mean discharge frequency can be one of the modes of encoding of information necessary for triggering of one efferent reaction or another, which are controlled by the hypothalamus. Examination of the BIA parameters of subcortical neurons, as well as comparison of the parameters of such an activity with the localization of cells and with the modality of stimulation that leads to modification of the IA, should allow one to reveal reasons for the formation and modification of the IA on neurons of the anterior hypothalamus. Since functional peculiarities of the neurons correlate with their BIA pattern, such data can provide an insight into the functional bases of the neurophysiological mechanisms underlying regulatory functions of the hypothalamus. Neirofiziologiya/Neurophysiology, Vol. 37, Nos. 5/6, pp. 463–474, September–December, 2005.     

Morphine-induced increase in D-1 receptor regulated signal transduction in rat striatal neurons and its facilitation by glucocorticoid receptor activation: Possible role in behavioral sensitization

One month (but not 1–3 days) after intermittent morphine administration, the hyperresponsiveness of rats toward the locomotor effects of morphine and amphetamine was associated with an increase in dopamine (DA) D-1 receptor-stimulated adenylyl cyclase activity and enhanced steady state levels of preprodynorphin gene expression in slices of the caudate/putamen and nucleus accumbens. Such an enduring increase in postsynaptic D-1 receptor efficacy also occurred in cultured γ-aminobutyric acid (GABA) neurons of the striatum obtained from rats prenatally treated with morphine. Interestingly, in vitro glucocorticoid receptor activation in these cultured striatal neurons by corticosterone potentiated this neuroadaptive effect of prior in vivo morphine exposure. Since activation of glucocorticoid receptors by corticosterone did not affect D-1 receptor functioning in cultured neurons of saline-pretreated rats, prior intermittent exposure to morphine (somehow) appears to induce a long-lasting state of corticosterone hyperresponsiveness in striatal neurons. Therefore, DA-sensitive striatal GABA neurons may represent common neuronal substrates acted upon by morphine and corticosterone. We hypothesize that the delayed occurrence of these long-lasting morphine-induced neuroadaptive effects in GABA/dynorphin neurons of the striatum is involved in the enduring nature of behavioral sensitization to drugs of abuse and cross-sensitization to stressors. Special issue dedicated to Dr. Eric J. Simon.     

A Possible Mechanism of Blocking of Limbic Motor Seizure Reactions Induced by Activation of the Thalamic Reticular Nucleus

Experiments were directed toward elucidation of the role of the thalamic reticular nucleus (R) in the modulation of generalized seizure reactions under kindling conditions and of the mechanisms mediating the effects of stimulation of the above nucleus on seizure activity. It was shown that activation of the thalamic R in rats limits generalization of the seizure reactions both in the course of development of seizures of limbic genesis (evoked by stimulation of the hippocampus) and under conditions of the existence of a pre-formed epileptic nidus. Tetanic stimulation of the R in cats under conditions of acute experiments induced significant facilitation of IPSPs in thalamo-cortical neurons of the ventrolateral thalamic nucleus. This effect is rather long-lasting and may be considered a mechanism providing blocking of generalized seizures under kindling conditions. Neirofiziologiya/Neurophysiology, Vol. 37, No. 4, pp. 352–361, July–August, 2005.     

Parameters for a model of an oscillating neuronal network in the cochlear nucleus defined by genetic algorithms

Chopper neurons in the cochlear nucleus are characterized by intrinsic oscillations with short average interspike intervals (ISIs) and relative level independence of their response (Pfeiffer, Exp Brain Res 1:220–235, 1966; Blackburn and Sachs, J Neurophysiol 62:1303–1329, 1989), properties which are unattained by models of single chopper neurons (e.g., Rothman and Manis, J Neurophysiol 89:3070–3082, 2003a). In order to achieve short ISIs, we optimized the time constants of Rothman and Manis single neuron model with genetic algorithms. Some parameters in the optimization, such as the temperature and the capacity of the cell, turned out to be crucial for the required acceleration of their response. In order to achieve the relative level independence, we have simulated an interconnected network consisting of Rothman and Manis neurons. The results indicate that by stabilization of intrinsic oscillations, it is possible to simulate the physiologically observed level independence of ISIs. As previously reviewed and demonstrated (Bahmer and Langner, Biol Cybern 95:371–379, 2006a), chopper neurons show a preference for ISIs which are multiples of 0.4 ms. It was also demonstrated that the network consisting of two optimized Rothman and Manis neurons which activate each other with synaptic delays of 0.4 ms shows a preference for ISIs of 0.8 ms. Oscillations with various multiples of 0.4 ms as ISIs may be derived from neurons in a more complex network that is activated by simultaneous input of an onset neuron and several auditory nerve fibers.     

Effects of coagulation of thelocus coeruleus and pontine raphe nuclei on the background activity recorded from the rat cerebellar fastigial nucleus neurons

Simultaneous or separate coagulation of thelocus coeruleus (LC) and the pontine raphe nucleus (PRN) results in a significant increase of irregular-type background activity in the cerebellar fastigial nucleus neurons. There are also considerable changes in the dynamics of impulse sequences, in particular, the number of neurons with random interpulse intervals markedly increases. Destruction of theLC and/or PRN is followed by a marked drop in the mean frequency of discharges in the neurons of the fastigial nucleus.Neirofiziologiya/Neurophysiology, Vol. 26, No. 6, pp. 437–442, November–December, 1994.     

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.     

Correlation between the Activity of Dopaminergic Neurons of the Ventral Tegmentum and Spectral Power of the EEG Rhythms in Awake Cats

We studied correlations between the frequency of background impulse activity (BIA) of dopaminergic (DAergic) neurons of the ventral tegmentum (VT) and spectral power (SP) of the frequency components of EEG samples recorded in awake cats. The EEG was recorded monopolarly (electrodes were fixed in the cranial bones) from the frontal, occipital, and right and left temporal regions of the cortex. In a great majority of the cases, the BIA frequency of VT DA-ergic neurons demonstrated significant positive correlations with changes in the SPs of the alpha and beta EEG rhythms. The closest correlations of the spiking frequency of DA-ergic cells with the SP of the alpha rhythm was observed in the occipital region, while those with the beta SP were found in the frontal area. Correlations of the activity of DA-ergic neurons with the SPs of the alpha and beta rhythms in the left temporal cortical zone were closer, as compared with those in the symmetrical right zone. Correlations of the SPs of the delta, theta, and gamma EEG components with the discharge frequency of VT DA neurons were of opposite directions, and in most cases such correlations did not reach the level of significance. The results of this study show that, in some cases, specific EEG patterns can be considered indicators of the state of the cerebral VT DA-ergic system. Neirofiziologiya/Neurophysiology, Vol. 40, No. 4, pp. 359–367, July–August, 2008.     

Effects of morphine on electrical activity of the emotion-producing zones in the hypothalamus of adult and aged rats

In the experiments performed on adult and aged rats, the effect of morphine on the electrical activity, recorded from the emotion-producing zones of the hypothalamus, the ventromedial nucleus (VMN), and the lateral hypothalamic area (LHA), was studied. In thein vitro experiments, an age-dependent reduction of background impulse activity (BIA) was found in the VMN single neurons, but not in the LHA neurons. Morphine reduced BIA in most of the VMN neurons, but enhanced it in the LHA neurons of adult rats, and enhanced BIA in the neurons of both structures of the aged rats. The inhibitory effect of morphine on the VMN and LHA neurons and its excitatory effect on the LHA neurons decreased with age. In thein vivo experiments, an age-dependent reduction of the background field electrical activity (background electrogram, BEG) was found in the neurons of both emotion-producing zones. Morphine reduced the BEG magnitude in the VMN and LHA more effectively in the aged rats than in the adult rats. The results allow us to suggest that both the opiate regulation of hypothalamic functions and formation of an opiate dependence in the adult rats essentially differ from those in the aged rats.Neirofiziologiya/Neurophysiology, Vol. 27, No. 2, pp. 126–133, March–April, 1995.     

Neurogenic Neuroprotection

1. Stimulation of the rostral-ventromedial pole of the cerebellar fastigial nucleus exerts powerful effects on systemic and cerebral circulation.2. Excitation of fibers passing through the fastigial nucleus evokes sympathoactivation and increases in arterial pressure.3. Increase in cerebral blood flow evoked by excitation of fibers passing through the FN is mediated by intrinsic brain mechanisms independently of metabolism.4. Excitation of the fastigial nucleus neurons in contrast decreases arterial pressure and cerebral blood flow. The latter probably is secondary to the suppression of brain metabolism.5. Excitation of the fastigial nucleus neurons significantly decreases damaging effects of focal and global ischemia on the brain.6. The fastigial nucleus-evoked neuroprotection can be conditioned: 1-h stimulation protects the brain for up to 3 weeks.7. Other brain structures such as subthalamic cerebrovasodilator area and dorsal periaqueductal gray matter also produce long-lasting brain salvage when stimulated.8. More than one mechanism may account for neurogenic neuroprotection.9. Early neuroprotection, which develops immediately after the stimulation, involves opening of potassium channels.10. Delayed long-lasting neuroprotection may involve changes in genes expression resulting in suppression of inflammatory reaction and apoptotic cascade.11. It is conceivable that intrinsic neuroprotective system exists within the brain, which renders the brain more tolerant to adverse stimuli when activated.12. Knowledge of the mechanisms of neurogenic neuroprotection will allow developing new neuroprotective approaches.     

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.     

Electrical activity in the vagus nerves and some medullary nuclei in rats: Changes induced by endotoxin action and hyperthermia evoked by an increase in ambient temperatures

Acute experiments on rats showed that intraperitoneal administration of 5 μg/kg of a bacterial toxin (pyrogenal) increases the afferent impulsation frequency in the cervical segments of vagus nerves, VN (multifiber recording), and frequency of the multineuronal activity in the solitary tract nucleus (STN); these changes were observed during the whole period of recording (10–160 min following toxin injection). Enhancement of the efferent impulsation in the VN and neuronal activity in the dorsal nucleus of the vagus nerve (DNVN) could be observed only 120–130 min after toxin administration. Under these conditions rectal temperature in experimental animals was 1.5° higher than that in control rats throughout the period of recording. Following subdiaphragmatic vagotomy, the afferent impulsation frequency in the cervical VN decreased about four times and kept on decreasing during the whole period of registration. Pyrogenal introduction evoked no changes in the direction of reactions to vagotomy. Under these conditions, body temperature of these animals was 2.5°C higher than in control vagotomized rats by the final stage of recording. Animal heating in a chamber caused no changes in the afferent impulsation frequency and resulted in a decrease in the frequency of VN efferent discharges. Involvement of the VN in the maintenance of temperature homeostasis during fever induced by the endotoxin action and by hyperthermia due to a rise in ambient temperature is discussed. Neirofiziologiya/Neurophysiology, Vol. 32, No. 2, pp. 112–119, March–April, 2000.     

Changes in the mitochondrial permeability in medullary cardiovascular neurons influence the hemodynamics in rats

In acute experiments on anesthetized rats, we studied the effects of modulation of the mitochondrial permeability in medullary cardiovascular neurons (nucl. tractus solitarii, NTS, nucl. ambiguus, AMB, paramedian reticular nucleus, PMn, and lateral reticular nucleus, LRN) on the systemic arterial pressure (SAP). We were the first to show that the mitochondrial permeability is essential for medullary cardiovascular control. An increase in the mitochondrial permeability with injections of an inductor of mitochondrial transition pore opening, phenylarsine oxide (PAO, 0.5 to 504 nmol), into the medullary nuclei resulted in long-lasting decreases in the SAP; at high doses of PAO, these drops could be irreversible and led to the animal’s death. Injections of an inhibitor of mitochondrial transition pore opening, melatonin (0.7 to 70.0 nmol), into the medullary nuclei induced dose-dependent increases in the SAP. Melatonin and L-arginine were shown to demonstrate neuroprotective effects due to their ability to attenuate the consequences of increased mitochondrial permeability in medullary cardiovascular neurons. Neirofiziologiya/Neurophysiology, Vol. 39, Nos. 4/5, pp. 392–395, July–October, 2007.     

Effect of the vermian cortex of the anterior lobe of the cerebellum on the background electrical activity of fastigial neurons

The effect of electrical stimulation of the vermian cortex of the anterior lobe of the cerebellum on the activity of neurons of different portions of the fastigial nucleus was studied in acute experiments on cats under light nembutal anesthesia. Inhibitory influences of the cortex (80.6% of the reacting neurons) were manifested in total blocking or decrease in the frequency of the background activity of the neurons and were characterized by a long aftereffect and "rebound." Stimulation of the cortex also had a blocking effect on the inhibitory interaction of adjacent nuclear elements. Facilitatory influences (14.5% of the neurons) were expressed either by an increase of spontaneous discharges of the neurons or by the appearance of activity in rhythm with the stimulation. The effectiveness of cortical stimulation depended on the localization of the stimulating electrodes. Zones of maximum density of projections to a given neuron of the nucleus and convergence and divergence of influences were found in the cerebellar cortex.L. A. Orbeli Institute of Physiology, Academy of Sciences of the Armenian SSR, Erevan. Translated from Neirofiziolgiya, Vol. 2, No. 3, pp. 260–268, May–June, 1970.