Changes in pyramidal tract response to direct stimulation of the sensomotor cortex of the rabbit during formation of a conditioned reflex

Changes of pyramidal tract (PT) response were analyzed, reflecting the final result of cortical interaction in the process of combinations of direct stimulations of cortical surface in nonimmobilized and unanaesthetized rabbits. It has been shown that in a situation, modelling conditioning, changes take place of the first direct component--the D-component--of the PT response (reflecting the excitability of the PT neurones), as well as changes of the successive indirect synaptic component--I-component (reflecting the excitability of presynaptic cortical elements and of intracortical synaptic connections). I-component changes were significantly more expressed. In most cases the I-component of the response was increased. The obtained data testify to an increase of synaptic efficiency in the process of temporary connection formation and to possible change (increase or reduction) of excitability of PT neurones.     

Reflection of the plastic properties of monosynaptically interconnected neurons in the statistical characteristics of their spike activity

By mathematical and biomathematical methods of neuronal interaction modelling, changes were studied of cross-correlation histograms (CCH) of impulse flows and of average interimpulse intervals of monosynaptically interconnected neurones, at changes of efficiency of forward and backward connections, of excitability of neurones and of summate action on them of independent random afferent synaptic inflows. It is shown, that a single sign of efficiency increase of monosynaptic excitatory or inhibitory connection between neurones (amplitude increase of the corresponding postsynaptic potential) consists in amplitude increase of the main peak or trough the rated CCH of their impulse flows, followed by a decrease of average interspike intervals of both neurones.     

Reflection of the plastic properties of very simple neuronal assemblies in the statistical characteristics of the spike activity of their elements. Monosynaptically connected neurons

Changes of cross-correlation histograms (CCH) of impulse trains and of mean interspike intervals (ISI) of monosynaptically connected neurones under changes of interneuronal connection efficiency, neuronal excitability and action on these neurones of independent irregular afferent synaptic inflows, were studied by methods of mathematical and biomathematical modelling of synaptic neuronal interaction (computer-controlled experiment on mollusc neurones). It was shown that statistical of increase of efficiency of monosynaptic excitatory or inhibitory interneuronal connection (amplitude enhancement of corresponding postsynaptic potential) is an increase of the main peak or trough of normalized CCH of impulse trains accompanied by a decrease of mean ISIs of both neurones.     

The active electrogenesis of the command neurons in the defensive behavior of the mollusk during conditioning]

In the paper changes of active electrogenesis of the command neurones of defensive closure of snail pneumostome at elaboration, extinction and repeated elaboration of classic conditioned defensive reflex to tactile stimulus was described; the tactile stimulation of other point of the body served as a differentiating stimulus. During the increase of biological significance of conditioned stimulus as a result of learning the stimulation of the command neurones in response to this stimulus was raised. At the same time the neurones showed decreased excitability in response to differentiating stimulus. Possible mechanisms of quick reconstruction of neurones excitability and functional value of PA generation threshold changes were discussed.     

Effect of serotonin on the activity of the neurons involved in the realization of the avoidance reflex of the snail

Bath application of 10(-5) mol/l of serotonin (5-HT) elicited a 50% increase of summary EPSPs recorded in command neurones for avoidance behaviour. No significant changes of rest potential and input resistance were seen in these cells. 5-HT evoked an increase of spontaneous level of firing in motoneurones involved in the same reflex, as well as an increase in the number of spikes which paralleled increase of EPSPs to the same stimulus in command neurones. In sensory cells, presynaptic to the command neurones, application of 5-HT evoked a significant increase of excitability and of input resistance. Monosynaptic EPSPs recorded in the command neurones showed a 40% increase after serotonin application. It is concluded that the major locus of plastic changes evoked by 5-HT application in the neuronal chain underlying avoidance reflex is the synaptic contact between sensory and command neurones.     

In vivo effects of Panax ginseng extracts on the cytochrome P450-dependent monooxygenase system in the liver of 2,3,7,8-tetrachlorodibenzo-p-dioxin-exposed guinea pig

The effects of the subchronic administration of Panax ginseng extracts were examined on the hepatic cytochrome P450-dependent monooxygenase system of guinea pigs pre-exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Panax ginseng extracts were intraperitoneally administered to guinea pigs at 100 mg/kg/day for 14 days from 1 week after a single intraperitoneal injection of 1 microg of TCDD/kg of body weight. TCDD treatment increased the total cytochrome P450 content 2.86-fold, and this was remarkably inhibited by the administration of Panax ginseng extracts. Treatment with ginseng extract alone also decreased the contents of cytochrome P450 by 33%, but both TCDD and ginseng extracts had no effect on cytochrome b(5) content. The administration of TCDD resulted in a 1.73-fold increase in microsomal NADPH-cytochrome P450 reductase activity in the guinea pig liver, and this was significantly inhibited by ginseng extracts, but treatment with ginseng extracts alone had no effect on its activity, and no statistical changes in the activity of NADPH-cytochrome b(5) reductase were observed in guinea pig liver due to TCDD and/or ginseng extract administration. Compared to the control, ECOD activity remarkably (1.76-fold) increased after TCDD administration, but this increase was completely inhibited by treatment with ginseng extract. Treatment with ginseng extract alone resulted in a 50% reduction of ECOD activity. TCDD administration remarkably induced benzphetamine demethylation (BPDM) activity, while ginseng extract also slightly increased the enzyme's activity, but the induction attributed to ginseng extracts was not statistically significant. Even though administration of ginseng extracts slightly inhibited TCDD-induced BPDM activity, the inhibition was not statistically significant. These results indicate that ginseng extract exerts different effect on the induction of P450 isozymes. From these results, we suggest that Panax ginseng extracts may act as an inhibitor of CYP1A rather than that of CYP2B.     

Depression of presynaptic excitation by the activation of vanilloid receptor 1 in the rat spinal dorsal horn revealed by optical imaging

Hypoxia alters neuronal function and can lead to neuronal injury or death especially in the central nervous system. But little is known about the effects of hypoxia in neurones of the peripheral nervous system (PNS), which survive longer hypoxic periods. Additionally, people have experienced unpleasant sensations during ischemia which are dedicated to changes in conduction properties or changes in excitability in the PNS. However, the underlying ionic conductances in dorsal root ganglion (DRG) neurones have not been investigated in detail. Therefore we investigated the influence of moderate hypoxia (27.0 ± 1.5 mmHg) on action potentials, excitability and ionic conductances of small neurones in a slice preparation of DRGs of young rats. The neurones responded within a few minutes non-uniformly to moderate hypoxia: changes of excitability could be assigned to decreased outward currents in most of the neurones (77%) whereas a smaller group (23%) displayed increased outward currents in Ringer solution. We were able to attribute most of the reduction in outward-current to a voltage-gated K⁺ current which activated at potentials positive to -50 mV and was sensitive to 50 nM α-dendrotoxin (DTX). Other toxins that inhibit subtypes of voltage gated K⁺ channels, such as margatoxin (MgTX), dendrotoxin-K (DTX-K), r-tityustoxin Kα (TsTX-K) and r-agitoxin (AgTX-2) failed to prevent the hypoxia induced reduction. Therefore we could not assign the hypoxia sensitive K⁺ current to one homomeric K_V channel type in sensory neurones. Functionally this K⁺ current blockade might underlie the increased action potential (AP) duration in these neurones. Altogether these results, might explain the functional impairment of peripheral neurones under moderate hypoxia.     

人参茎叶提取物对刺参生长、免疫及抗病力的影响

以初始体重为(4.910.17) g的刺参(Apostichopus japonicas)为研究对象,研究投喂不同剂量人参茎叶提取物对刺参生长、免疫及抗病力的影响,探讨人参茎叶提取物在刺参养殖中的应用。在每千克基础饲料中分别添加10、20、40和80 g人参茎叶提取物作为实验组,并以基础饲料为对照进行为期30d的饲喂养殖。结果显示,投喂人参茎叶提取物对刺参的生长并无显著影响,刺参特定生长率不随人参茎叶提取物添加量的增加而提高。当人参茎叶提取物添加量为80 g/kg时,刺参体腔细胞总数、呼吸暴发强度、细胞吞噬活性、超氧化物歧化酶活力、总一氧化氮合酶活力均显著高于对照组(P0.05);当人参茎叶提取物添加量为40 g/kg时,细胞吞噬活性也显著高于对照组(P0.05),但其余免疫指标与对照组相比无显著差异(P0.05);当人参茎叶提取物的添加量不大于20 g/kg时,各项免疫指标与对照组之间均无显著差异(P0.05)。攻毒实验表明, 20、40和80 g/kg人参茎叶提取物组的健康率要高于对照组,其中80 g/kg人参茎叶提取物组健康率为80.56%要显著高于对照组和10 g/kg人参茎叶提取物组(P0.05)。人参茎叶提取物可作为免疫增强剂应用于刺参的养殖中来提高刺参的免疫和抗病能力。       

Reflection of the plastic properties of the simplest neuronal associations in statistical characteristics of the spike activity of their elements. Polysynaptically linked neurons

Changes of crosscorrelation histograms of trains of action potentials and mean interspike intervals of polysynaptically connected neurones were studied by means of mathematical modelling of synaptic neuronal interaction at changes of efficiency of interneuronal monosynaptic connections, at changes of neuronal excitability, and at changes of total action on them of independent disorderly afferent synaptic inflows. Increase of amplitude of the main maximum (minimum) of the normalized crosscorrelation histogram of trains of action potentials accompanied by reduction of mean interspike intervals of both neurones, was shown to be a unsignificant indication of an increase of efficiency of polysynaptic excitatory (inhibitory) connections between the neurones (due to modification of synapses or to a change of the functional state of interneurones).     

Effect of a ginseng tissue culture preparation on morphofunctional changes in motor neurons upon activation

Irritation for 10 min of the posterior spinal root in the frog Rana temporaria (electrical stimulation 50 imp/sec, threshold power 4) results in decreasing size of the motoneurons and their nuclei and in appearing pycnomorphous type of neurons. Simultaneously, peculiar changes in cellular ultrastructure connected with inhibition of protein synthesis are observed. When the ginseng preparation is administered to intact animals, an increased excitability of the spinal centers, as well as increasing volume of the motoneuronal nuclei and certain ultrastructural shifts demonstrating activation of protein synthesis and cellular energy are observed. When the ginseng preparation is preliminary administered to the frogs, before a high-frequency synaptic activation of the motoneurons, it protects the cells from pathological changes and pycnotic shrinkage.     

Properties of a symmetric pair of serotonin-containing neurones in the cerebral ganglia of Planorbis.

1. There is a bilaterally symmetric pair of large serotonin-containing neurones in the cerebral ganglia of Planorbis corneus. 2. In some animals these neurones are connected by a non-rectifying electrotonic synapse, and fire in synchrony even at prolonged high frequency. In other animals the neurones are not coupled, and fire independently except when driven by common input. Occasionally the coupling is weak. 3. Both coupled and non-coupled serotonin neurones have processes in the major nerve trunks of both buccal ganglia. 4. Synapses are made with many neurones in the buccal ganglia. The serotonin neurones can initiate firing in several motoneurones and thus produce movements of the buccal mass. 5. During spontaneous feeding cycles the input and firing pattern of the serotonin neurones do not bear any obvious relation to the movements of the buccal mass. 6. The data suggest that the serotonin neurones are modulatory cells, altering the level of excitability of buccal ganglion neurones.     

Effect of the microiontophoretic application of acetylcholine on the formation of conditioned reactions in motor cortex neurons

In alert rabbits the activity of the motor cortex neurones was recorded with simultaneous application of acetylcholine to them in the process of defensive conditioning. Conditioned reorganization, mainly of activation type, were found in 60% of neurones. In most cases conditionally reacting cells were sensitive to acetylcholine. Ionophoretic application of the transmitter promoted the formation of conditioned neuronal responses and increased them in comparison with conditioned reactions evoked in absence of acetylcholine. It is supposed that the influence of acetylcholine on conditioned cellular process is realized due to its action on the state of excitability of the cortical neurones.     

Functional significance of the serotoninergic influence on neuronal activity of the somatosensory cortex in 12-day-old kittens

Monoamines, which participate in synaptic transmission as transmitters, also accomplish the modulation of neuronal activity. The role of serotonin (5-hydroxytryptamine--5-HT) was investigated in 8 to 14-day-old kittens by means of iontophoretic application onto neurones of the somatosensory cerebral cortex. The most typical response was the inhibition of neuronal activity. Another type of reaction was generated by inhibitory interneurones. After the microiontophoretic application of 5-HT, the tonic response of cortical neurones to the stimulation of the sciatic nerve changed into a phasic response. It is being suggested that the application of 5-HT to cortical neurones increases the excitability of inhibitory neurones. Hence, the serotoninergic regulation of neuronal activity in the somatosensory cortex may be operational from the 11th to the 12th day of postnatal life in cats.     

3,4-Diaminopyridine induced stimulus-bound repetitive firing in frog sympathetic ganglion: no changes in postsynaptic membrane excitability

It has been shown previously that 3,4-diaminopyridine (3,4-DAP) facilitates synaptic transmission in the frog sympathetic ganglion inducing so-called stimulus-bound repetition (SBR), i.e. a brief burst of repetitive postganglionic discharges after a single orthodromic stimulus. In the present study we analyzed one of the possible mechanisms of the 3,4-DAP-induced SBR, namely changes in postsynaptic membrane excitability. We found that 3,4-DAP in concentration optimal for inducing SBR (2 X 10(-4) mol.l-1) had no direct effect on the excitability of the postsynaptic membrane of frog sympathetic neurones. The excitability was expressed as the threshold for action potentials elicited orthodromically, antidromically and directly, as well as the spike activity evoked by constant depolarizing current pulses. We also indirectly excluded the involvement of two other possible mechanisms of neuronal membrane excitability modulation in the 3,4-DAP-induced SBR, i.e. the M-current suppression by analyzing the participation of muscarinic receptor activation in the SBR, and inhibition of the Ca(2+)-activated K+ currents by measuring the duration of afterhyperpolarization of antidromic action potential. Our findings indicate that no remarkable changes in the properties of the postsynaptic membrane contribute to the generation of 3,4-DAP-induced SBR in the frog sympathetic ganglion. This strongly supports the hypothesis that the mechanism underlying SBR evoked by this drug is presynaptic.     

The analysis of the impulse activity of 2 neurons monosynaptically excitable by a 3rd using cross-correlation histograms and Cox's method. The potential for detecting neuronal and synaptic plasticity

By a method of mathematical modelling exogenic stationary random single impulse activity was reproduced of two neurones (N1 and N2), monosynaptically excited by a third one (N3). Value P12, defined from cross-correlation histogram and Cox coefficient beta 12 were used to evaluate the degree of dependence of N1 and N2 impulse trains. Dynamics of P12, beta 12 and of values of P1*, P2* and P3* proportional to corresponding mean interimpulse intervals of N1, N2 and N3, was studied under changes of efficiency of interneuronal connections, neurones excitability and summate action on them of independent random afferent synaptic inflows. It has been shown that the increase (decrease) of P12 or beta 12 accompanied by decrease (increase) of P1* and P2* is a sign of plastic change or N3 discharges frequency, or a sign of plastic changes of the amplitude of excited postsynaptic potentials elicited by these discharges.     

Generation of ginsenosides Rg3 and Rh2 from North American ginseng

Rg3 and Rh2 ginsenosides are primarily found in Korean red ginseng root (Panax ginseng C.A. Meyer) and valued for their bioactive properties. We quantified both Rh2 and Rg3 ginseng leaf and Rg3 from root extracts derived from North American ginseng (Panax quinquefolius). Quantification was obtained by application of HPLC with ion fragments detected using ESI-MS. Ginseng leaf contained 11.3+/-0.5 mg/g Rh2 and 7.5+/-0.9 mg/g Rg3 in concentrated extracts compared to 10.6+/-0.4 mg/g Rg3 in ginseng root. No detectable Rh2 was found in root extracts by HPLC, although it was detectable by ESI-MS analysis. Ginsenosides Rg3 and Rh2 were detected following hot water reflux extraction, but not from tissues extracted with 80% aqueous ethanol at room temperature. Therefore ginsenosides Rg3 and Rh2 are not naturally present in North American ginseng, but are products of a thermal process. Using ESI-MS analysis, it was found that formation of Rg3 and Rh2, among other compounds, were a function of heating time and were breakdown products of the more abundant ginsenosides Rb1 and Rc. Our findings that heat processed North American ginseng leaf is an excellent source of Rh2 ginsenoside is an important discovery considering that ginseng leaf material is obtainable throughout the entire plant cycle for recovery of valuable ginsenosides for pharmaceutical use.     

Mycotoxins in root extracts of American and Asian ginseng bind estrogen receptors alpha and beta

The estrogenic activity of ginseng has been the subject of conflicting reports. Cell proliferation, induction of estrogen-responsive genes, and isolated cases of adverse reactions such as postmenopausal vaginal bleeding and gynecomastia have been reported after ginseng treatment. Other studies report antiproliferative effects with no induction of estrogen-responsive genes. We developed estrogen receptor (ER) alpha and ER alpha competitive binding assays using recombinant receptors and [(3)H]-17 alpha-estradiol to detect phytoestrogens in extracts of Asian ginseng root (Panax ginseng C. A. Meyer) and American ginseng root (Panax quinquefolius L.). Root extracts contained substances that bound both receptor isoforms. These substances had a two to three times greater affinity for ER alpha. Significantly higher binding was found in methanol extracts than in hot water extracts. Subsequent analysis of the extracts revealed significant ER binding attributable to zearalenone, the estrogenic mycotoxin produced by several Fusarium species. The ER showed no binding affinity for Rb1 and Rg1, the major ginsenosides found in P. quinquefolius and P. ginseng, respectively. Thus, ginseng extraction methods, plant species tested, and mycotoxin contaminants may help to explain the disparate literature reports. The prevalence and health significance of fungal contamination in herbal products used for medicinal purposes should be further investigated.     

Dynamics of changes in the excitability of Helix lucorum neurons in response to an analog of vasopressin

Application of desglycine-arginine-vasopressin to spontaneously nonactive command neurones of the snail's defensive reflex in the process of low-frequency (2-4 min intervals) intracellular stimulation led under certain conditions to an increase of excitability that was expressed in the shortening of latency of action potential generation, increase of the number of action potentials in response to a stimulus of fixed value, increase of membrane resistance, lowering of critical level of membrane depolarization and amplifying of pacemaker activity. However in spite of unidirectional changes of all the recorded parameters, the increases of values, opposite to the latency, did not correlate with the increases of membrane resistance and correlated well with the changes of depolarization critical level. If desglycine arginine-vasopressin was added to the medium during worsening of the neurones' excitability was probably caused by the influence of desglycine-arginine-vasopressin on the membrane active properties.     

Possibilities of detecting the plasticity of monosynaptic excitable connections during the analysis of impulse activity of neurons using cross-correlation histograms and Cox's method

By the method of mathematical modelling, stationary irregular exogenous impulse activity of two monosynaptically connected neurones (N1 and N2; excitatory connection) was reproduced. The degree of impulse flows N1 and N2 dependence was estimated by the value P12, proportional to the height of crosscorrelation histogram peak, and by Cox's coefficient beta 12. The dynamics was studied of P12, beta 12 and of values P1* and P2*, proportional to mean interpulse intervals of N1 and N2, at changes of connection efficiency, neurones excitability and of influence of afferent synaptic bombardment on them. The following signs of modification of existing between N1 and N2 monosynaptic excitatory connection were established: 1) change of P12 in direction opposite to that of P1* and P2* change; 2) differently directed changes of beta 12 and P2* of postsynaptic N2.