Conflicting effects of excitatory synaptic and electric coupling on the dynamics of square-wave bursters

Using two-cell and 50-cell networks of square-wave bursters, we studied how excitatory coupling of individual neurons affects the bursting output of the network. Our results show that the effects of synaptic excitation vs. electrical coupling are distinct. Increasing excitatory synaptic coupling generally increases burst duration. Electrical coupling also increases burst duration for low to moderate values, but at sufficiently strong values promotes a switch to highly synchronous bursts where further increases in electrical or synaptic coupling have a minimal effect on burst duration. These effects are largely mediated by spike synchrony, which is determined by the stability of the in-phase spiking solution during the burst. Even when both coupling mechanisms are strong, one form (in-phase or anti-phase) of spike synchrony will determine the burst dynamics, resulting in a sharp boundary in the space of the coupling parameters. This boundary exists in both two cell and network simulations. We use these results to interpret the effects of gap-junction blockers on the neuronal circuitry that underlies respiration.     

Afferent connections to the fast conduction pathway in the central nervous system of the leech Hirudo medicinalis

A burst of all-or-none action potentials, identical in size and shape, can be recorded from the ventral cord of H. medicinalis following both photic and mechanical stimulation of the skin. This response propagates both anteriorly and posteriorly from its point of origin at the same conduction velocity of about 1.3 m/sec. The action potential elicited by electrical stimulation of the cord collides by refractoriness with the action potentials elicited in response to photic and mechanical stimulation. The cord response to photic and mechanical stimulation is reversibly suppressed by perfusion with high Mg++ solutions, whereas the afferent discharges recorded from the segmental nerves remain unaffected. Lesion experiments show that the cord responses to mechanical and photic stimuli, travel along the median connective (Faivre's nerve). It is concluded that afferent impulses originating from mechanoreceptors and photoreceptors converge with chemical excitatory synapses onto a fast conducting pathway in the ventral cord. This fast conducting pathway is coextensive with the one which is excited by electrical stimulation of the ventral cord (1, 3).     

Regulation of Electrical Bursting in a Spatiotemporal Model of a GnRH Neuron

Gonadotropin-releasing hormone (GnRH) neurons are hypothalamic neurons that control the pulsatile release of GnRH that governs fertility and reproduction in mammals. The mechanisms underlying the pulsatile release of GnRH are not well understood. Some mathematical models have been developed previously to explain different aspects of these activities, such as the properties of burst action potential firing and their associated Ca²⁺ transients. These previous studies were based on experimental recordings taken from the soma of GnRH neurons. However, some research groups have shown that the dendrites of GnRH neurons play very important roles. In particular, it is now known that the site of action potential initiation in these neurons is often in the dendrite, over 100 μm from the soma. This raises an important question. Since some of the mechanisms for controlling the burst length and interburst interval are located in the soma, how can electrical bursting be controlled when initiated at a site located some distance from these controlling mechanisms? In order to answer this question, we construct a spatio-temporal mathematical model that includes both the soma and the dendrite. Our model shows that the diffusion coefficient for the spread of electrical potentials in the dendrite is large enough to coordinate burst firing of action potentials when the initiation site is located at some distance from the soma.     

The origin of spontaneous synchronized burst in cultured neuronal networks based on multi-electrode arrays

Many neural networks in mammalian central nervous system (CNS) fire single spike and complex spike burst. In fact, the conditions for triggering burst are not well understood. In the paper multi-electrode arrays (MEA) are used to record the spontaneous electrophysiological activities of cultured rat hippocampal neuronal network for a long time. After about 3 weeks culture, a transition from single spike to burst is observed in several networks. All of these spikes fire quickly before burst begins. The firing rate during the burst is lower than that just before the burst, but differences of inter-spike intervals (ISIs) between two firing patterns are not clear. Moreover, the electrical activities on neighboring electrodes show strong synchrony during the burst activities. In a word, the generation of the burst requires that network should have a sufficient level of excitation as well as a balance of synaptic inhibition.     

Integral characteristics of the cardiac electrical excitation wave]

A set of characterisitics of the cardiac electrical generator is described which expresses in an integral form some important properties of the electrical excitation wave, in particular its summary intensity, average spatial localization and distinction from a uniform double layer with planar rim. Relation of the proposed model to the multipole equivalent generator is discussed, and procedures for computing its characteristics are given. Calculation results for these characteristics on the basis of experimentally measured electrical field potentials of isolated dog hearts are presented.     

Pituitary adenylate cyclase-activating peptide enhances electrical coupling in the mouse adrenal medulla

Neuroendocrine adrenal medullary chromaffin cells receive synaptic excitation through the sympathetic splanchnic nerve to elicit catecholamine release into the circulation. Under basal sympathetic tone, splanchnic-released acetylcholine evokes chromaffin cells to fire action potentials, leading to synchronous phasic catecholamine release. Under elevated splanchnic firing, experienced under the sympathoadrenal stress response, chromaffin cells undergo desensitization to cholinergic excitation. Yet, stress evokes a persistent and elevated adrenal catecholamine release. This sustained stress-evoked release has been shown to depend on splanchnic release of a peptide transmitter, pituitary adenylate cyclase-activating peptide (PACAP). PACAP stimulates catecholamine release through a PKC-dependent pathway that is mechanistically independent of cholinergic excitation. Moreover, it has also been reported that shorter term phospho-regulation of existing gap junction channels acts to increase junctional conductance. In this study, we test if PACAP-mediated excitation upregulates cell-cell electrical coupling to enhance chromaffin cell excitability. We utilize electrophysiological recordings conducted in adrenal tissue slices to measure the effects of PACAP stimulation on cell coupling. We report that PACAP excitation increases electrical coupling and the spread of electrical excitation between adrenal chromaffin cells. Thus PACAP acts not only as a secretagogue but also evokes an electrical remodeling of the medulla, presumably to adapt to the organism's needs during acute sympathetic stress.     

Laser-Interferometric Re-examination of Rapid Conductance of Excitation in Mimosa pudica

The correlation between electrical excitation and turgor changesin plants has been investigated with a novel combination ofan electrometer and a laser-interferometer. With a resolutionof about 10 nm, no significant correlation could be detectedbetween the passage of action potentials and physical movementin the excitation conducting stem of Mimosa pudica. Apart frommarginal observations, the results render an hydraulic conductanceof excitation unlikely; they rather confirm the primary roleof electrical events in rapid conductance of excitation in higherplants. Key words: Laser-interferometer, turgor movement, action potential, osmotic relations     

EEG-correlates of alimentary behavior in rabbits with different levels of hunger and satiety]

The electrical activity of the rabbit brain at different stages of hunger and satiation was correlated with the animal's behavioral reactions. It has been found that alimentary reactions are attended with the appearance of complex high-amplitude and high-frequency electrical potentials in the lateral hypothalamic area, which increased with the longer duration of the animal's hunger, as well as during search, in response to natural and conditioned alimentary stimuli, and when feeding. As satiation sets in, they fade and disappear after food refusal. It is assumed that this form of activity is an EEG expression of alimentary motivational excitation. Its constituent rhythms reflect the different components of alimentary excitation.     

Primitive nervous systems: Peripheral habituation in decerebrate polyclad flatworms

The response to a vibration stimulus recorded from the cords of the ventral submuscular plexus of the polyclad flatworm, Notoplana acticola, consists of a burst of action potentials. The response can be abolished by the application of MgCl₂ to the sea water bathing the preparation. With repeated application of the stimulus, decreasing numbers of action potentials can be measured. This waning responsiveness can be dishabituated by applying a more intense vibration stimulus or with electrical shocks applied directly to the ventral nerve plexus. With electrical stimuli a number of shocks have to be applied before the response can be dishabituated. Changes in responsiveness can be measured simultaneously in a number of sites in the plexus even after the nerves between recording sites have been severed. With different interstimulus intervals the extent of habituation changes. As interstimulus intervals increase from 1 to 5 sec, there appears to be a decrease in responsiveness which recovers when interstimulus intervals become longer than 5 sec.     

Synaptic effects evoked by supraspinal and intraspinal stimulation in lamprey motoneurons

In experiments onLampetra fluviatilis in response to electrical stimulation of bulbar reticulospinal neurons and descending fibers the postsynaptic potentials of segmental motoneurons and action potentials of single intraspinal axons were recorded intracellularly and the cord dorsum potentials were recorded by a surface electrode. Fast-conducting reticulospinal axons (Müller's axons) were shown to excite spinal motoneurons monosynaptically. Monosynaptic reticulo-motoneuronal EPSPs arise as the result of excitation of a limited number of descending fibers, they reproduce high frequencies of stimulation readily and, in some cases, they are divided into components of which the first may be attributed to an electrical, and the second to a chemical mechanism of transmission. Besides early monosynaptic EPSPs, late, probably polysynaptic, responses also are found.     

Synchronous Ca(2+) oscillation emerges from voltage fluctuations of Ca(2+) stores

Synchronous Ca(2+) oscillation occurs in various cell types to regulate cellular functions. However, the mechanism for synchronization of Ca(2+) increases between cells remains unclear. Recently, synchronous oscillatory changes in the membrane potential of internal Ca(2+) stores were recorded using an organelle-specific voltage-sensitive dye [Yamashita et al. (2006) FEBS J273, 3585-3597], and an electrical coupling model of the synchronization of store potentials and Ca(2+) releases has been proposed [Yamashita (2006) FEBS Lett580, 4979-4983]. This model is based on capacitative coupling, by which transient voltage changes can be synchronized, but oscillatory slow potentials cannot be communicated. Another candidate mechanism is synchronization of action potentials and ensuing Ca(2+) influx through voltage-dependent Ca channels. The present study addresses the question of whether Ca(2+) increases are synchronized by action potentials, and how oscillatory store potentials are synchronized across the cells. Electrophysiological and Ca(2+)-sensitive fluorescence measurements in early embryonic chick retina showed that synchronous Ca(2+) oscillation was caused by releases of Ca(2+) from Ca(2+) stores without any evidence of action potentials in retinal neuroepithelial cells or newborn neurons. High-speed fluorescence measurement of store membrane potential surprisingly revealed that the synchronous oscillatory changes in the store potential were periodic repeats of a burst of high-frequency voltage fluctuations. The burst coincided with a Ca(2+) increase. The present study suggests that synchronization of Ca(2+) release is mediated by the high-frequency fluctuation in the store potential. Close apposition of the store membrane and plasma membrane in an epithelial structure would allow capacitative coupling across the cells.     

Membrane voltage and neurotransmitter regulation of neuronal growth cone motility

The neurotransmitters serotonin and dopamine inhibit growth cone motility and neurite elongation of specific identified neurons of the pond snail Helisoma. Similarly, experimentally evoked action potentials inhibit motility of these growth cones. Here we explore the possibility that the motility- and elongation-inhibiting actions of serotonin and dopamine derive from the electrophysiological responses of the respective neurons. Evidence of three types in support of this hypothesis is presented: (1) Only those identified neurons for which motility is inhibited by serotonin or dopamine respond to the transmitter with sustained electrical excitation. (2) The magnitude of the electrical excitation response correlates with the degree of inhibition of growth cone motility. (3) The injection of hyperpolarizing current enables motility to continue as in the absence of transmitters. We conclude that membrane voltage is an important level of control of growth cone motility, at which neurotransmitters exert a regulatory influence.     

Investigation of burst generation by the electrically coupled cyberchron network in the snail Helisoma using a single-electrode voltage clamp

This paper describes the results of investigating burst generation by the cyberchron network in the snail Helisoma. The cyberchron network is composed of approximately 20 electrically coupled neurons and controls the feeding behavior of the snail. The electrical coupling between network members has made it particularly difficult to distinguish between the importance and involvement of single-cell and network properties in burst generation by this system. The present investigations utilized the new single-electrode voltage clamp to examine the membrane properties and network interactions of the cyberchron neurons: (1) A slow outward current is activated by moderately large depolarizing commands (?40 to 0 mV) and does not undergo inactivation decay (i.e., decline in magnitude) during a command potential step maintained for 10 sec or more. The lack of inactivation of the outward current in cyberchron neurons appears to be due to the dominating role of a Ca-dependent K current. (2) There are two functionally distinct classes of cyberchrons—current generator cyberchrons and follower cyberchrons. (3) Primary current generator cyberchrons have membrane properties similar to endogenous bursting neurons (e.g., persistent inward Ca current and negative resistance region in I–V plot) and appear to provide the main driving and timing current for the rest of the network. (4) The vast majority of cyberchrons are secondary current generator cyberchrons with membrane properties which exhibit inward-going rectification and appear to burst as a result of regenerative excitation with one another and the primary current generator cyberchrons. (5) The second class of cyberchrons are driven by the electrical synaptic input from the current generator cyberchrons, do not exhibit inward-going rectification, and are called follower cyberchrons. (6) Burst termination is due to activation of a slow outward tail current in most cyberchrons during the burst (probably Ca-activated K current) which causes a hyperpolarization in individual cyberchrons, terminating the burst. (7) Decay of the outward tail current causes the cyberchrons to depolarize, which activates the persistent inward Ca current in the primary current generator cyberchrons, starting the burst cycle anew.     

A spectral-correlational analysis of the EEG of the neocortex in the rabbit in a state of thirst

Summate electrical activity of the rabbit neocortex during formation of drinking excitation was studied by means of mathematical analysis. It is shown that the change of the electrical activity depends on the level of drinking excitability created by various duration of water deprivation (24-48 h) and is expressed in a generalized lowering of potentials amplitude without frequency change. Spectro-correlative EEG analysis showed that lowering of spectrum power took place within the whole analyzed frequencies range. Besides, an increase took place of interconnections of the cortical electrical processes, estimated by coherence function. It may by suggested that the manifested reconstruction of spectro-correlative characteristics of the neocortical biopotentials reflects a formation of motivational excitation establishing optimal level of cortex functioning.     

Antidromic vasodilation caused by A-delta afferents in the frog

In anesthetized immobilized frog we recorded changes in hind leg volume evoked by electrical stimulation of peripheral end of the sciatic nerve. The ranges of the stimulus amplitudes sufficient to induce vasodilator or vasoconstrictor reactions were estimated. In a separate set of experiments thresholds of A alpha beta, A delta and C-afferent fibers excitation were evaluated by recording waves of compound action potentials in VIII-X dorsal roots. It was found that vasodilation is elicited by the stimuli of virtually the same intensity range as the excitation of A delta afferent fibers, including low threshold one. Consequently we concluded that in frog these myelinated afferent fibers are capable of dilating the blood vessels by antidromic action. This finding is in contrast with antidromic vasodilation in mammals which is known to result mainly from the impulses of the unmyelinated afferent fibers.     

Ionic mechanisms of endogenous bursting in CA3 hippocampal pyramidal neurons: a model study

A critical property of some neurons is burst firing, which in the hippocampus plays a primary role in reliable transmission of electrical signals. However, bursting may also contribute to synchronization of electrical activity in networks of neurons, a hallmark of epilepsy. Understanding the ionic mechanisms of bursting in a single neuron, and how mutations associated with epilepsy modify these mechanisms, is an important building block for understanding the emergent network behaviors. We present a single-compartment model of a CA3 hippocampal pyramidal neuron based on recent experimental data. We then use the model to determine the roles of primary depolarizing currents in burst generation. The single compartment model incorporates accurate representations of sodium (Na(+)) channels (Na(V)1.1) and T-type calcium (Ca(2+)) channel subtypes (Ca(V)3.1, Ca(V)3.2, and Ca(V)3.3). Our simulations predict the importance of Na(+) and T-type Ca(2+) channels in hippocampal pyramidal cell bursting and reveal the distinct contribution of each subtype to burst morphology. We also performed fast-slow analysis in a reduced comparable model, which shows that our model burst is generated as a result of the interaction of two slow variables, the T-type Ca(2+) channel activation gate and the Ca(2+)-dependent potassium (K(+)) channel activation gate. The model reproduces a range of experimentally observed phenomena including afterdepolarizing potentials, spike widening at the end of the burst, and rebound. Finally, we use the model to simulate the effects of two epilepsy-linked mutations: R1648H in Na(V)1.1 and C456S in Ca(V)3.2, both of which result in increased cellular excitability.     

Interstitial potentials and their change with depth into cardiac tissue.

The electrical source strength for an isolated, active, excitable fiber can be taken to be its transmembrane current as an excellent approximation. The transmembrane current can be determined from intracellular potentials only. But for multicellular preparations, particularly cardiac ventricular muscle, the electrical source strength may be changed significantly by the presence of the interstitial potential field. This report examines the size of the interstitial potential field as a function of depth into a semi-infinite tissue structure of cardiac muscle regarded as syncytial. A uniform propagating plane wave of excitation is assumed and the interstitial potential field is found based on consideration of the medium as a continuum (bidomain model). As a whole, the results are inconsistent with any of the limiting cases normally used to represent the volume conductor, and suggest that in only the thinnest of tissue (less than 200 micron) can the interstitial potentials be ignored.     

Unresponsive, a behavioral mutant in Xenopus laevis: electrophysiological studies of the neuromuscular system

Normal Xenopus laevis embryos begin movements at 1 day after fertilization. Embryos homozygous for the unresponsive mutation fail to move until 4 days after fertilization (just prior to feeding), after which they recover slowly. Electrophysiological studies were undertaken to determine the focus of this mutation. Formamide treatment of normal embryos was used to produce a phenocopy of the unresponsive condition, permitting direct comparisons between mutant and normal embryos. Intracellular recordings from muscle cells were obtained in formamide-treated and untreated preparations with both normal and unresponsive animals. Local electrical stimulation evoked either isolated endplate potentials and action potentials or after-discharges of these events in all preparations. A decrease in illumination also caused a burst of endplate potentials and action potentials. Therefore, the electrophysiology of the neuromuscular junction in unresponsive appears qualitatively normal; the effect of the mutation on the motor system is probably distal to the neuromuscular junction, either at or subsequent to excitation-contraction coupling.     

The spectral correlation characteristics of the brain electrical activity in the rabbit during thirst]

Spectral-correlation analysis of the summate electrical activity of a number of subcortical structures of rabbit brain, having, by literature data, a relation to drinking behaviour showed that the increase of drinking excitability, induced by water deprivation was accompanied by definite reconstruction of biopotentials. In electrical activity of the studied structures, the spectrum power, as a rule, decreased (except in the paraventricular nucleus), and a definite structure of coherent connections between the subcortical and cortical potentials was established. Among the studied subcortical formations, structures (anterior hypothalamic area, lateral preoptic area, medial preoptic area, paraventricular nucleus) could be singled out where reconstructions of spectral characteristics of biopotentials took place most regularity, and the electrical processes in which were characterised by coherence index by an increase of spatial interconnection with the neocortex potentials, what allows to consider them as most significant for organization of drinking excitation.     

Lateral inhibition shapes the oscillatory responses of the horseshoe crab's compound eye

The synchronized response of the compound eye of the horseshoe crab to uniform illumination arises from the integration of excitation with the strong lateral inhibition present in many specimens. At the higher levels of excitation, the steady production of nerve impulses by individual eccentric cells is often replaced by periodically recurring volleys of impulses. This behavior is shown here to be the result of the temporal behavior of the post-synaptic potentials responsible for lateral inhibition. For a broad class of inhibitory potentials, a simple condition is established which separates potentials which permit volleys at high excitation levels from those which support only the steady production of impulses throughout the physiological range of excitations.