Morphologic differences in the cutaneous receptors of low- and high-excitability lines of rats

By means of methylene blue staining of the rat plantar skin, receptor terminals in lines with low- and high-excitability have been revealed with a subsequent morphometric and cytophotometric estimation of the dye sorption degree. Divergence of the signs at selection according to excitability of the nervous-muscular apparatus is spreading to the peripheral nervous system elements, affecting its structural and tinctorial indices. In rats with low threshold of excitability increasing size of the receptor plates and areas of the receptors division is observed in comparison to the animals with high threshold of excitability. The receptors in the former line are stained less intensively than the receptors in the latter line.     

Open-field behavior of rats with different levels of nervous system excitability

The dependence was studied of characteristics of organization of orienting-investigating behaviour in the open field test on the level of nervous system excitability in rats selected by the threshold of excitability of the peripheral nervous system. It is established that the studied rats lines can be divided into groups according to entropy level of their behaviour. Rats of highly excitable line build their behaviour in highly probable stereotypes as compared with the animals of low-excitable line, which organize their behaviour with more plasticity, diversity. Differences in the nervous system excitability influence first of all the organization of animals behaviour.     

The action of the neurotoxins 5,6-dihydroxytryptamine and p-chlorophenylalanine on the electrical activity parameters of the command neurons during long-term sensitization and learning in the snail]

The influence of 5,6-dihydroxytryptamine (5,6-DHT), which selectively destroyed serotonin terminals, and p-chlorphenylalanine, which inhibited serotonin synthesis, was studied on the long-term sensitization (LTS) in a snail. The membrane mechanisms were analyzed by measuring electrical characteristics of command neurons of defensive behavior LPa3, RPa3, LPa2, and RPa2. Snails injected with saline served as an active control. It was shown that the injected drugs inhibited the LTS in certain concentrations. A significant increase was observed in the membrane potential and the threshold of the action potential generation in the command neurons after 5,6-DHT injection in the doses of 20 and 30 mg/kg (in comparison with the active control). Sensitization of snails injected with saline solution led to the LTS and decrease in the membrane and threshold potentials of the command neurons. After the LTS, changes in membrane and threshold potentials in snails injected with 5,6-DHT were negligible in comparison with those injected with 5,6-DHT but without the LTS. Neither the LTS nor subsequent learning resulted in a further decrease in membrane and threshold potentials. Thus, the neurotoxin injection led to an increase in excitability of command neurons and their depolarization, and the LDS did not elicit further excitability increase. Since the shifts of the threshold and membrane potentials were the same, it was concluded that the increase in membrane excitability was induced by the depolarizing shift of the membrane potential.     

Action potential conduction velocity along the caudal and tibial nerves in rat strains selected for excitability of the neuromuscular system

The study was performed on 2 lines of rat selected for high (H) and low (L) excitability threshold of the nervous-muscle apparatus. H-line rats have higher values of spike conduction velocity in caudal and tibial nerves, as compared to those obtained in L-line rats. It is suggested that behavioral differences between these two lines of rat may be connected with changes of neurological characters both of peripheral and central nervous system, as a result of selection.     

Effect of weak static magnetic fields on the excitability of a neuron

Changes in the excitability of the neuron (amplitude, excitability threshold, rate of action potential transduction), as well as changes in the viscosity of the plasma membrane of the nerve and membranes of subcellular organelles, induced by the action of a weak magnetic field, have been studied by the methods of extracellular registration of membrane potential and combination scattering. It was found that only the threshold of excitability in intact nervous fibers increases by the action of this field. It was proven that the conformation of C40 carotenoids localized not only in plasma membranes but also in subcellular membranes of the neuron changes in a weak magnetic field. It is assumed that the changes in the excitability of the neuron by the action of weak magnetic field are due to changes in the orderliness of membrane lipids and the content of oxygen in the cytoplasm.     

Low-intensity repetitive transcranial magnetic stimulation decreases motor cortical excitability in humans.

Repetitive transcranial magnetic stimulation of the motor cortex (rTMS) can be used to modify motor cortical excitability in human subjects. At stimulus intensities near to or above resting motor threshold, low-frequency rTMS (approximately 1 Hz) decreases motor cortical excitability, whereas high-frequency rTMS (5-20 Hz) can increase excitability. We investigated the effect of 10 min of intermittent rTMS on motor cortical excitability in normal subjects at two frequencies (2 or 6 Hz). Three low intensities of stimulation (70, 80, and 90% of active motor threshold) and sham stimulation were used. The number of stimuli were matched between conditions. Motor cortical excitability was investigated by measurement of the motor-evoked potential (MEP) evoked by single magnetic stimuli in the relaxed first dorsal interosseus muscle. The intensity of the single stimuli was set to evoke baseline MEPs of approximately 1 mV in amplitude. Both 2- and 6-Hz stimulation, at 80% of active motor threshold, reduced the magnitude of MEPs for approximately 30 min (P < 0.05). MEPs returned to baseline values after a weak voluntary contraction. Stimulation at 70 and 90% of active motor threshold and sham stimulation did not induce a significant group effect on MEP magnitude. However, the intersubject response to rTMS at 90% of active motor threshold was highly variable, with some subjects showing significant MEP facilitation and others inhibition. These results suggest that, at low stimulus intensities, the intensity of stimulation may be as important as frequency in determining the effect of rTMS on motor cortical excitability.     

代谢抑制剂对有尾类胚胎表皮细胞兴奋性的影响

It has been reported that the cells in atypical epidermis, which developed from the in vitro cultured ectoderm isolated at early gastrula, showed very low excitability or were even non-excitable at 6 V when examined electro-physiologically. If non-excitable explants were treated with energy supplying substances, such as glucose, the action potential (AP) appeared quickly. It indicates that, the excitability of epidermis cells is related to their energy metabolism. In order to verify the above proposition the effects of metabolic inhibitors on the excitability of the epidermis cells were examined using electrophysiological technique. Two kinds of explants were used: explants which developed from the epidermis underlaid with mesoderm isolated at early neurula (epidermis vesicle) and explant which developed from the ectoderm isolated at early gastrula (atypical epidermis). In all experiments explants were stimulated extracellularly and APs were recorded intracellularly. The specimens were stimulated with electric stimulus at 6 V first, and, if they displayed AP, the strength was lowered to determine the stimulus threshold to evoke AP. The duration of stimulus was fixed at 1 ms. The ratio of the resting potential value during treatment to the original value was taken as index of change level of the resting potential (RP). During treatment of epidermis vesicle with 1 mM NaN3 or 1 mM NaCN or 0.1 mM 2,4-dinitrophenol (DNP), the excitability of the epidermis cells was reduced: the stimulus threshold gradually increased and the cells in most explants lost the excitability. The cells became excitable after the drugs were washed out.(ABSTRACT TRUNCATED AT 250 WORDS)     

Developmental changes in intrinsic excitability of principal neurons in the rat medial nucleus of the trapezoid body

The calyx of Held synapse is a giant axosomatic synapse that has a fast relay function within the sound localization circuit of the brainstem. In the adult, each principal neuron of the medial nucleus of the trapezoid body (MNTB) is contacted by a single calyx terminal. In rodents, the calyx of Held synapse forms around the third postnatal day (P3). Here, we studied the developmental changes in the intrinsic excitability of the principal neurons during the first postnatal week by making whole-cell recordings from brainstem slices. In slices from P0-1 rats, about 20% of the principal neurons were spontaneously active, whereas after P3, no spontaneously active cells were observed. Already at P0, principal neurons received both glutamatergic and GABAergic/glycinergic inputs. The occurrence of spontaneous action potentials depended upon the presence of spontaneous glutamatergic inputs; summation of only a few quanta was enough to reach action potential threshold. The main cause for this high excitability was a high resting membrane resistance, which decreased at least four-fold during the first postnatal week. A relatively slow decay of synaptic currents and a relatively depolarized membrane potential may have contributed as well. We conclude that the decrease in the excitability of principal neurons in the MNTB matches the increase of the strength of the synaptic inputs resulting from the formation and maturation of the calyx of Held synapse during the first postnatal week. This decrease in excitability will make it progressively more difficult for non-calyceal inputs to trigger action potentials.     

An endogenous elevation of cGMP increases the excitability of identified insect neurosecretory cells

In the moth, Manduca sexta, the neuropeptide, eclosion hormone, triggers a dramatic rise in the levels of intracellular cGMP within a group of 50 neurons. The cells within this group include the segmentally repeated neurosecretory cell, Cell 27. In this study the effect of cGMP on the excitability of Cell 27 was investigated using intracellular recordings. Prior to its normal elevation in cGMP, Cell 27 exhibited a high spike threshold, but this was lowered dramatically when intracellular cGMP levels increased. The latter was also associated with spontaneous action potentials. This change in excitability did not correspond with changes in either resting potential, input resistance, or action potential amplitude. A similar lowering of threshold was induced by perfusion of 8-bromo-cGMP, whereas 8-bromo-cAMP caused the threshold to increase. Intracellular recordings using various ion substitution paradigms and channel blockers provided evidence which suggests indirectly that Ca²⁺ is mostly responsible for the depolarizing phase of the action potential while a Ca²⁺-activated K⁺ current contributes to the hyperpolarization. The results of these manipulations are consistent with the hypothesis that cGMP may partially increase excitability in Cell 27 by enhancing an inward Ca²⁺ current. Accepted: 31 October 1996     

Excitability of septo-hippocampal axon terminals: changes as a function of the level of neuronal activity

The septo-hippocampal terminals were electrically stimulated at the level of the gyrus dentatus in urethane anesthetized rats and antidromic responses were recorded in the medial septum. The excitability of the terminals was assessed by the threshold of terminal antidromic activation. An increase in the discharge frequency of the septal neurons following a microiontophoretic application of glutamate to their soma induced an increase in the antidromic activation threshold, i.e. a decrease in excitability of the terminals. An application of GABA which inhibited septal neuronal activity, induced a decrease in the antidromic activation threshold, i.e. an increase in the terminal excitability of septo-hippocampal neurons. These results are discussed in the light of the presynaptic autoreceptor hypothesis.     

Changes in the electrical properties of atrial trabecula induced by an electric stimulus]

Electrical activity, excitation threshold and "steady--state" current-voltage, relationship (estimated under voltage clamp conditions) in the membrane of chicken embryo atrial trabecula were investigated by means of double succrose-gap technique. Application of short (10 msec) electrical stimuli with magnitudes up to 6.10(-5) a (1-150 threshold) resulted in increased excitability and appearance of spontaneous activity. Release of neurotransmitters and polarity of the applied sitmulus are shown not to play a significant role in the changes in membrane excitability observed, the main cause of the latter being the increased sodium permeability of the membrane.     

Variable synaptic strengths controls the firing rate distribution in feedforward neural networks

Heterogeneity of firing rate statistics is known to have severe consequences on neural coding. Recent experimental recordings in weakly electric fish indicate that the distribution-width of superficial pyramidal cell firing rates (trial- and time-averaged) in the electrosensory lateral line lobe (ELL) depends on the stimulus, and also that network inputs can mediate changes in the firing rate distribution across the population. We previously developed theoretical methods to understand how two attributes (synaptic and intrinsic heterogeneity) interact and alter the firing rate distribution in a population of integrate-and-fire neurons with random recurrent coupling. Inspired by our experimental data, we extend these theoretical results to a delayed feedforward spiking network that qualitatively capture the changes of firing rate heterogeneity observed in in-vivo recordings. We demonstrate how heterogeneous neural attributes alter firing rate heterogeneity, accounting for the effect with various sensory stimuli. The model predicts how the strength of the effective network connectivity is related to intrinsic heterogeneity in such delayed feedforward networks: the strength of the feedforward input is positively correlated with excitability (threshold value for spiking) when firing rate heterogeneity is low and is negatively correlated with excitability with high firing rate heterogeneity. We also show how our theory can be used to predict effective neural architecture. We demonstrate that neural attributes do not interact in a simple manner but rather in a complex stimulus-dependent fashion to control neural heterogeneity and discuss how it can ultimately shape population codes.     

Asymmetry in Signal Propagation between the Soma and Dendrites Plays a Key Role in Determining Dendritic Excitability in Motoneurons

It is widely recognized that propagation of electrophysiological signals between the soma and dendrites of neurons differs depending on direction, i.e. it is asymmetric. How this asymmetry influences the activation of voltage-gated dendritic channels, and consequent neuronal behavior, remains unclear. Based on the analysis of asymmetry in several types of motoneurons, we extended our previous methodology for reducing a fully reconstructed motoneuron model to a two-compartment representation that preserved asymmetric signal propagation. The reduced models accurately replicated the dendritic excitability and the dynamics of the anatomical model involving a persistent inward current (PIC) dispersed over the dendrites. The relationship between asymmetric signal propagation and dendritic excitability was investigated using the reduced models while varying the asymmetry in signal propagation between the soma and the dendrite with PIC density constant. We found that increases in signal attenuation from soma to dendrites increased the activation threshold of a PIC (hypo-excitability), whereas increases in signal attenuation from dendrites to soma decreased the activation threshold of a PIC (hyper-excitability). These effects were so strong that reversing the asymmetry in the soma-to-dendrite vs. dendrite-to-soma attenuation, reversed the correlation between PIC threshold and distance of this current source from the soma. We propose the tight relation of the asymmetric signal propagation to the input resistance in the dendrites as a mechanism underlying the influence of the asymmetric signal propagation on the dendritic excitability. All these results emphasize the importance of maintaining the physiological asymmetry in dendritic signaling not only for normal function of the cells but also for biophysically realistic simulations of dendritic excitability.     

The relationship between the formation of trace reactions and the functional state of rats of different genetic lines]

The level of excitability of the nervous system was enhanced in rats of the Krushinsky--Molodkina (K--M) and Wistar (W) lines by means of dynamic and static physical loads and injections of different doses of al-amphetamine. It was shown that a higher level of excitability of the central nervous system produced in both lines of rats improved memory and increased the rate of formation of a conditioned active aboidance reflex (CAAR). A greater physical load or dose of the stimulant drug in the K-M line of rats resulted in a decrease of all parameters characterizing CAAR, while in the other line they rose in progression. The data obtained are believed to be related to a different genetically conditioned initial level of excitability in the indicated lines of rats--a higher one in the K--M line animals as compared with the W line rats, which determines a different norm of the nervous system responsiveness in the indicated groups of animals.     

Dissociation of motor task-induced cortical excitability and pain perception changes in healthy volunteers

Background

There is evidence that interventions aiming at modulation of the motor cortex activity lead to pain reduction. In order to understand further the role of the motor cortex on pain modulation, we aimed to compare the behavioral (pressure pain threshold) and neurophysiological effects (transcranial magnetic stimulation (TMS) induced cortical excitability) across three different motor tasks.

Methodology/Principal Findings

Fifteen healthy male subjects were enrolled in this randomized, controlled, blinded, cross-over designed study. Three different tasks were tested including motor learning with and without visual feedback, and simple hand movements. Cortical excitability was assessed using single and paired-pulse TMS measures such as resting motor threshold (RMT), motor-evoked potential (MEP), intracortical facilitation (ICF), short intracortical inhibition (SICI), and cortical silent period (CSP). All tasks showed significant reduction in pain perception represented by an increase in pressure pain threshold compared to the control condition (untrained hand). ANOVA indicated a difference among the three tasks regarding motor cortex excitability change. There was a significant increase in motor cortex excitability (as indexed by MEP increase and CSP shortening) for the simple hand movements.

Conclusions/Significance

Although different motor tasks involving motor learning with and without visual feedback and simple hand movements appear to change pain perception similarly, it is likely that the neural mechanisms might not be the same as evidenced by differential effects in motor cortex excitability induced by these tasks. In addition, TMS-indexed motor excitability measures are not likely good markers to index the effects of motor-based tasks on pain perception in healthy subjects as other neural networks besides primary motor cortex might be involved with pain modulation during motor training.     

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.     

Calcium signal-dependent plasticity of neuronal excitability developed postnatally

Neuronal plasticity and its development were investigated at pyramidal neurons in the cortical slices of rats. The threshold and probability of firing spikes were measured by using whole-cell recording to assess neuronal excitability. Postsynaptic high frequency activity (HFA) at the pyramidal neurons, evoked by 20 trains (250-ms interval) of five depolarization-pulses (1 ms) at 100 Hz, persistently lowered the threshold and increased the probability of firing spikes. After long-term enhancement of neuronal excitability by HFA was stable, another HFA induced further enhancement. Infusing 1 mM 1,2-bis(2-aminophenoxy)-ethane-N, N,N',N'-tetraacetic acid or 100 microM CaMKII(281-301) into the recording neurons prevented HFA-induced long-term enhancement of neuronal excitability. The infusion of 40 microM calcineurin autoinhibitory peptide enhanced neuronal excitability, which occluded HFA effect. HFA-induced long-term enhancement of intrinsic excitability expressed at most pyramidal neurons after postnatal day (PND) 14, but not at those before PND 9. Our results show a new type of neuronal plasticity induced by physiological activity at cortical neurons, which requires calcium-dependent protein phosphorylation and develops during postnatal period. An upregulation of intrinsic excitability at cortical neurons facilitates their activity and broadens signal codes; consequently, their computational ability is upgraded.     

Effect of firing rate on the calcium permeability in adult neurons during spontaneous action potentials.

Calcium channels in neurons mediate a wide variety of essential functions. In addition to contributing to action potential shape, they furnish a substrate that acts as an intracellular second messenger. This study shows that the shape of the neuronal action potential has characteristics that promote long openings of L-type (high threshold) calcium channels. We also present evidence that a change in the firing rate of isolated neurons modulates gating of single calcium channels. This mechanism could be important in modulating neuron excitability and providing a rise in intracellular Ca, when needed.