Coding with spike shapes and graded potentials in cortical networks

In cortical neurones, analogue dendritic potentials are thought to be encoded into patterns of digital spikes. According to this view, neuronal codes and computations are based on the temporal patterns of spikes: spike times, bursts or spike rates. Recently, we proposed an 'action potential waveform code' for cortical pyramidal neurones in which the spike shape carries information. Broader somatic action potentials are reliably produced in response to higher conductance input, allowing for four times more information transfer than spike times alone. This information is preserved during synaptic integration in a single neurone, as back-propagating action potentials of diverse shapes differentially shunt incoming postsynaptic potentials and so participate in the next round of spike generation. An open question has been whether the information in action potential waveforms can also survive axonal conduction and directly influence synaptic transmission to neighbouring neurones. Several new findings have now brought new light to this subject, showing cortical information processing that transcends the classical models.     

Changes in the configuration of conditioned reactions of visual cortex neurons during changes in reinforcement parameters]

In order to study the influences of controlled changes of defensive integration on the activity of visual cortical units their responses to a conditioned light flash and electric cutaneous stimulation with a 600 msec interval between them were recorded in experiments on alert rabbits. It has been shown that in a third of the neurones the types of reaction to light flashes and electric stimuli coincide. The changes in parameters of the reinforcing shock led to a changed response of most cells to the conditioned photic stimulus and electric stimulation. The changes may have affected units which produce any activation phase, including cells with activity characteristic of detectory ("simple" and "complex") visual neurones. The data obtained suggest that the special function of the visual cortex is used in different ways in systemic mechanisms of conditioned and unconditioned defensive acts and that the integrated system of a behavioral act exerts control both on the use of the unit in a certain systemic process and on its receptive field.     

Conditioned feedback and inhibitory reorganization of the receptive fields of the cortical neurons as a basis for the subconscious change in the thresholds of visual recognition and detection

In the paper three groups of facts are compared: significant adaptative and adaptational modification of receptive fields of cat's visual cortex neurones, conditioned selective subsensory change of the threshold of perception (detection and recognition) of a letter by man in relation to two control ones and the role of spatially specialized cortical inhibition in formation and adaptative modifications of receptive fields and detector properties of the visual cortex neurones. Interconnection is discussed of the phenomena described as well as community of their mechanisms.     

Synchronization dynamics in the neuronal work of the neocortex and hippocampus during learning before and after the administration of nootropics and narcotics

The basal difference in action of the studied drugs was that nootropics (phenybut in a dose of 40 mg/kg and pyracetam in a dose of 200-400 mg/kg) did not change the initial action of pain reinforcement on synchronism in responses of the cortical neurones of alert nonimmobilized rabbits by inhibitory type (coincidence of the presence and absence of impulse activity) towards its decrease, while narcotics of various types (ethanol in a dose of 4-6 mg/kg, morphine-like opiate DAGO and opioid peptide DADLE in doses of 250 mkg/kg) eliminated the action of pain reinforcement on synchronism in responses of the cortical neurones both by inhibitory and activation (time of coincidence only of the presence of impulse activity) types. These and other drugs mainly weakened the initial action of both the inhibitory and reinforced light flashes of synchronism in neurones activity both by inhibitory and activation types. There was no constant parallelism between changes of synchronization and the frequency of the cortical impulses.     

Computer simulation of flagellar movement VIII: coordination of dynein by local curvature control can generate helical bending waves

Computer simulations have been carried out with a model flagellum that can bend in three dimensions. A pattern of dynein activation in which regions of dynein activity propagate along each doublet, with a phase shift of approximately 1/9 wavelength between adjacent doublets, will produce a helical bending wave. This pattern can be termed "doublet metachronism." The simulations show that doublet metachronism can arise spontaneously in a model axoneme in which activation of dyneins is controlled locally by the curvature of each outer doublet microtubule. In this model, dyneins operate both as sensors of curvature and as motors. Doublet metachronism and the chirality of the resulting helical bending pattern are regulated by the angular difference between the direction of the moment and sliding produced by dyneins on a doublet and the direction of the controlling curvature for that doublet. A flagellum that is generating a helical bending wave experiences twisting moments when it moves against external viscous resistance. At high viscosities, helical bending will be significantly modified by twist unless the twist resistance is greater than previously estimated. Spontaneous doublet metachronism must be modified or overridden in order for a flagellum to generate the planar bending waves that are required for efficient propulsion of spermatozoa. Planar bending can be achieved with the three-dimensional flagellar model by appropriate specification of the direction of the controlling curvature for each doublet. However, experimental observations indicate that this "hard-wired" solution is not appropriate for real flagella.     

The characteristics of the neuronal reactions of the cat somatosensory cortex to a heteromodal complex conditioned signal]

On alert cats the change was studied of the activity of the neurones of the sensorimotor cortical area at instrumental reaction to a simultaneous heteromodal complex stimulus. It was shown that in the projection of distal limb areas a group could be singled out of neurones, which changed their activity in one direction depending on the character of presented signals. In these cells an increase of discharges frequency was observed in response to complex stimulus, consisting of light and sound signals. After the extinction of the motor reaction both to the complex stimulus and to its components neuronal reactions of lesser intensity was recorded, what determined the absence of the motor reaction. This group of neurones had receptive fields localized on distal limb areas, it was activated at fulfillment of the movement of catching the reinforcement and belonged to neurones of the pyramidal tract. The neurones with receptive fields on the whole limb surface or changing their activity at the animal pose change, had variable reactions to positive and differentiation stimuli.     

IL-8 release of HL-60 cells treated with electric currents of different wave forms

Human promyelocytic leukaemia HL-60 cells which have been differentiated by DMSO to granulocytes were used to investigate the effect of different waveforms on the release of interleukine-8 (IL-8). The cells were prestimulated with 100 pM fMLP and subsequently treated for 15 min with different electrical fields and currents. Three hours later the release of IL-8 into the medium was determined by ELISA. Varying the frequency of the sinusoidal electrical current between 0 and 20 Hz resulted in 2 maxima of IL-8 release at 5 and 13 Hz. Prestimulated cells were treated with sine-, triangular-, and rectangular-waveforms at 5 Hz in the current intensity range of 0-3 mA/cm(2). For the three waveforms tested, the IL-8 release was enhanced 1.5 fold. Treatment of the cells with capacitively coupled electric fields of 5 Hz using field strengths between 0 and 10 V(eff)/cm had no effect on the release of IL-8. In comparison to the positive results after sine wave exposure alone, an exposure with sine wave current to which noise had been superimposed had no effect on the HL-60 cells. From these investigations it can be concluded that for electrical current treatment of prestimulated HL-60 cells the release of IL-8 does not depend on the waveform if the waveform information is not destroyed by superimposed noise.     

Changes in the activity of rat cortical and hippocampal neurones after the iontophoretic administration of beta-endorphin, glutamate and GABA

The effect of microiontophoretically administered beta-endorphin on the activity of 62 cortical and hippocampal neurones was studied in acute experiments on 14 rats. The effectiveness of beta-endorphin was first of all verified in the isolated guinea pig ileum, the mouse was deferens and in a study if its analgetic and catatonic effect in rats. Beta-endorphin only mildly depressed the spontaneous activity of cortical neurones, but markedly inhibited the activity stimulated by the microiontophoretic administration of glutamate. In the hippocampus, beta-endorphin stimulated the activity of all the studied neurones when only low ejection currents were used and activation persisted for 1-4 min after terminating administration. With higher ejection currents, the discharge frequency rose enormously and not even GABA blocked this effect. The excitatory effect of beta-endorphin on the hippocampal neurones may possibly be the basis of the epileptogenic action of this substance.     

Experimental investigation on neural cell survival after dielectrophoretic trapping

Negative dielectrophoretic forces can effectively be used to trap cortical rat neurons. The creation of dielectrophoretic forces requires electric fields of high non-uniformity. High electric field strengths, however, can cause excessive membrane potentials by which cells may unrecoverably be changed or it may lead to cell death. In a previous study it was found that cells trapped at 3 Vtt/14 MHz did not change morphologically as compared to cells that were not exposed to the electric field. This study investigates the viability of fetal cortical rat neurons after being trapped by negative dielectrophoretic forces at frequencies up to 1 MHz. A planar quadrupole micro-electrode structure was used for the creation of a non-uniform electric field. The sinusoidal input signal was varied in amplitude (3 and 5 Vtt) and frequency (10 kHz-1 MHz). The results presented in this paper show that the viability of dielectrophoretically trapped postnatal cortical rat cells was greatly frequency dependent. To preserve viability frequencies above 100 kHz (at 3 Vtt) or 1 MHz (5 Vtt) must be used.     

Electric fields induce curved growth of Enterobacter cloacae, Escherichia coli, and Bacillus subtilis cells: implications for mechanisms of galvanotropism and bacterial growth.

Directional growth in response to electric fields (galvanotropism) is known for eukaryotic cells as diverse as fibroblasts, neurons, algae, and fungal hyphae. The mechanism is not understood, but all proposals invoke actin either directly or indirectly. We applied electric fields to bacteria (which are inherently free of actin) to determine whether actin was essential for galvanotropism. Field-treated (but not control) Enterobacter cloacae and Escherichia coli cells curved rapidly toward the anode. The response was both field strength and pH dependent. The direction of curvature was reversed upon reversal of field polarity. The directional growth was not due to passive bending of the cells or to field-induced gradients of tropic substances in the medium. Field-treated Bacillus subtilis cells also curved, but the threshold was much higher than for E. cloacae or E. coli. Since the curved morphology must reflect spatial differences in the rates of cell wall synthesis and degradation, we looked for regions of active wall growth. Experiments in which the cells were decorated with latex beads revealed that the anode-facing ends of cells grew faster than the cathode-facing ends of the same cells. Inhibitors of cell wall synthesis caused spheroplasts to form on the convex regions of field-treated cells, suggesting that the initial curvature resulted from enhanced growth of cathode-facing regions. Our results indicate that an electric field modulates wall growth spatially and that the mechanism may involve differential stimulation of wall growth in both anode- and cathode-facing regions. Electric fields may therefore serve as valuable tools for studies of bacterial wall growth. Use of specific E. coli mutants may allow dissection of the galvanotropic mechanism at the molecular level.     

Elastic Properties of the Sea Urchin Sperm Flagellum

The theory of flexural vibrations in thin rods, applied to the movement of flagella, has been extended to include an investigation of the influence of the boundary conditions on the theoretical waveforms. It was found that for flagella which are flexible enough, the flexibility can be estimated solely from the wavelength of the wave traveling in it. This can be expected to hold for those flagella which do not possess a fibrous sheath. The bending moment in flagella in which the ampitude of the wave is maintained as the wave travels distally is almost completely produced by active contractile elements. This means that the active bending moment can be estimated from the radius of curvature of the flagellum and the stiffness. The above findings were applied to the case of the sea urchin sperm flagellum. One finds that the stiffness of the flagellum is caused mainly by the nine longitudinal fibers which must have a Young's modulus of slightly less than 10⁸dyne/cm². The longitudinal fibers need to develop a tension of 1.6 × 10⁸dyne/cm² to account for the bending moment in the flagellum. These two figures are in line with those found for muscle fibers.     

Cholinergic regulation of the activity of somatosensory cortex neurons during early postnatal ontogeny of the cat

In 11-14 days kittens, about 20% of neurones in the somatosensory cortical zone react to stimulation of subpallidal region which is a source of cholinergic projections to the cerebral cortex. The effect of subpallidal region stimulation is reproduced in case of microiontophoretic acetylcholine application and blocked by atropine what points to its cholinergic nature. Cholinergic stimulation causes inhibition of the background and evoked activities of the cortical neurones while, as it is known, in adult cats, acetylcholine mainly stimulates a reaction of activation. It is postulated that in kittens at the end of the second week of postnatal development, cholinergic innervation of the cortex significantly differs from the definitive one by its quantitative and functional parameters.     

Effect of bradykinin and morphine on rat sensomotor cortex neurons]

As revealed in acute experiments on rats bradykinin applied microiontophoretically produced neuronal activation in the sensory-motor region of the rat brain cortex. Morphine applied iontophoretically prevented bradykinin effect. It is suggested that bradykinin interacts with opiate receptors in the cortical neurones.     

Numerical evaluation of currents induced in a worker by ELF non‐uniform electric fields in high voltage substations and comparison with experimental results

An ungrounded human, such as a substation worker, receives contact currents when touching a grounded object in electric fields. In this article, contact currents and internal electric fields induced in the human when exposed to non‐uniform electric fields at 50 Hz are numerically calculated. This is done using a realistic human model standing at a distance of 0.1–0.5 m from the grounded conductive object. We found that the relationship between the external electric field strength and the contact current obtained by calculation is in good agreement with previous measurements. Calculated results show that the contact currents largely depend on the distance, and that the induced electric fields in the tissues are proportional to the contact current regardless of the non‐uniformity of the external electric field. Therefore, it is concluded that the contact current, rather than the spatial average of the external electric field, is more suitable for evaluating electric field dosimetry of tissues. The maximum induced electric field appears in the spinal cord in the central nervous system tissues, with the induced electric field in the spinal cord approaching the basic restriction (100 mV/m) of the new 2010 International Commission on Non‐Ionizing Radiation Protection guidelines for occupational exposure, if the contact current is 0.5 mA. Bioelectromagnetics 34:61–73, 2013. © 2012 Wiley Periodicals, Inc.     

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.     

Quantal release of ATP in mouse cortex

Transient currents occur at rest in cortical neurones that reflect the quantal release of transmitters such as glutamate and gamma-aminobutyric acid (GABA). We found a bimodal amplitude distribution for spontaneously occurring inward currents recorded from mouse pyramidal neurones in situ, in acutely isolated brain slices superfused with picrotoxin. Larger events were blocked by glutamate receptor (AMPA, kainate) antagonists; smaller events were partially inhibited by P2X receptor antagonists suramin and PPADS. The decay of the larger events was selectively prolonged by cyclothiazide. Stimulation of single intracortical axons elicited quantal glutamate-mediated currents and also quantal currents with amplitudes corresponding to the smaller spontaneous inward currents. It is likely that the lower amplitude spontaneous events reflect packaged ATP release. This occurs with a lower probability than that of glutamate, and evokes unitary currents about half the amplitude of those mediated through AMPA receptors. Furthermore, the packets of ATP appear to be released from vesicle in a subset of glutamate-containing terminals.     

Neurochemically distinct myenteric neurone populations containing calbindin have specific distribution patterns around the circumference of the gastric corpus

We recently described calbindin immunoreactivity in the myenteric plexus of the guinea-pig stomach. To study the neurochemical coding of calbindin D28 k (CALB)-containing myenteric neurones, the presence of calretinin (CALRET), choline acetyltransferase (ChAT), enkephalin (ENK), neuropeptide Y, serotonin (5-HT), somatostatin (SOM) and substance P(SP) was investigated immunohistochemically in colchicine-treated preparations. Nitric oxide synthase-containing neurones were detected by NADPH-diaphorase histochemistry. In addition, we investigated the neurone distribution patterns around the gastric corpus. Most CALB neurones were ChAT positive. ChAT/CALB neurones were either CALRET (ca 75%) or 5-HT positive and most contained in addition SP and/or ENK. All 5-HT neurones contained CALB. CALB labelled on average 2.3, 4.8 and 7.5 neurones per ganglion at the lesser curvature, in the central region and the greater curvature, respectively, which indicated a preferential localisation at the greater curvature. Compared to the total number of myenteric neurones, the proportion of CALB neurones increased significantly from the lesser curvature (6%) towards the greater curvature (18%). This shift, although observed for most ChAT/CALB-positive populations, was most prominent for the ChAT/CALB/CALRET/SP/ENK-encoded neurones. SOM-positive and ChAT-only encoded neurones were preferentially located at the lesser curvature. The remaining ten neurochemically defined populations did not exhibit an uneven distribution. The colocalisation of CALB with CALRET or 5-HT is specific for myenteric neurones in the stomach and represents one significant difference to the neurochemical code of CALB neurones in the guinea-pig intestine. The functional significance of the unevenness of neurone distribution along the circumference of the gastric corpus remains to be studied.     

GABA is toxic for mouse striatal neurones through a transporter-mediated process

In the present study, GABA was shown to induce a necrotic neuronal death in cultured striatal neurones from mouse embryos. This effect did not depend on the activation of GABA(A), GABA(B) or GABA(C) receptors as it was neither antagonized by bicuculline, saclofen or picrotoxin, respectively, nor reproduced by the GABA receptor agonists, muscimol and baclofen. Excluding the participation of glutamate, GABA neurotoxicity persisted in the presence of either the antagonists of ionotropic and metabotropic glutamate receptors or glutamate pyruvate transaminase, which induces an immediate catabolism of glutamate. A GABA transport-associated process is involved in GABA neurotoxicity as nipecotic acid and NO 711, two inhibitors of the high-affinity neuronal GABA transporters (GAT-1, in particular), completely prevented the neurotoxic effect of GABA. The activation of a subset of G proteins is also implicated in the GABA transport-mediated neuronal death as GABA neurotoxicity was completely suppressed when striatal neurones were pre-treated with pertussis toxin. Further demonstrating the specificity of this neurotoxic process, GABA-induced neurotoxicity was not observed in cortical neurones which, in contrast to striatal neurones, are largely represented by glutamatergic neurones. In conclusion, our study suggests that glutamate is not the sole neurotransmitter that can be responsible for brain damage and that GABA neurotoxicity involves both GABA transport and G protein transduction pathways.     

On thermofield electron emission from metal microtips

The electric field in the vicinity of a cone apex has an integrable singularity. Therefore, in order to calculate the thermofield emission current from a conical tip, it is necessary to find the emission current density at extremely high electric fields at the cone apex. In this paper, an original method for correctly calculating the electric field near a perfect conical tip and a tip with a rounded apex is proposed. A universal numerical approach to calculating thermionic, field, and thermofield electron emission from metal in a wide range of surface electric fields is offered. It is shown that, at high electric fields, the thermofield current density tends to a certain limiting (saturated) value, and the reason for this saturation is revealed. It is found that, for moderate fields, the total electron emission current from a conical tip is determined by the current from the immediate vicinity of the apex and depends substantially on the curvature radius of its rounding.     

Physiological studies of cortical spreading depression

Cortical spreading depression (CSD) produces propagating waves of transient neuronal hyperexcitability followed by depression. CSD is initiated by K+ release following neuronal firing or electrical, mechanical or chemical stimuli. A triphasic (30-50 s) cortical potential transient accompanies localized transmembrane redistributions of K+, glutamate, Ca2+, Na+, Cl- and H+. Accumulated K+ in the restricted interstitial space can cause both further neuronal depolarisation and inward movement of K+ into astrocytes that buffers this increased extracellular K+ concentration ([K+])o. However, astrocyte interconnections may then propagate the CSD wave by K+ liberation through an opening of remote K+ channels by volume, Ca2+ or N-methyl-D-aspartate receptor activation. Changes in cerebral blood volume and in apparent water diffusion co-efficient (ADC) accompanying CSD were first studied using magnetic resonance imaging (MRI) in whole lissencephalic brains. Diffusion-weighted echoplanar imaging in gyrencephalic brains went on to demonstrate CSD features that paralleled classical migraine aura. The ADC activity persisted minutes/hours post KCl stimulus. Pixelwise analyses distinguished single primary events and multiple, spatially restricted, slower propagating, secondary events whose detailed features varied with the nature of the originating stimulus. These ADC changes varied reciprocally with T2*-weighted (i.e. referring to spin-spin relaxation times) waveforms reflecting local blood flow. There followed prolonged decreases in cerebral blood flow culminating in late cerebrovascular changes blocked by the antimigraine agent sumatriptan. CSD phenomena have possible translational significance for human migraine aura and other cerebral pathologies such as the peri-infarct depolarisation events that follow ischaemia and brain injury.