Inhibitory Coupling Research Articles

Spike-train bifurcation scaling in two coupled chaotic neurons

We investigate the variation of the out-of-phase periodic rhythm produced by two chaotic neurons (Hindmarsh-Rose neurons [J. L. Hindmarsh and R. M. Rose, Proc. R. Soc. London B 221, 87 (1984)]) coupled by electrical and reciprocally synaptic connections. The exploration of a two-parametric bifurcation diagram, as a function of the strength of the electrical and inhibitory coupling, reveals that the periodic rhythms associated to the limit cycles bounded by saddle-node bifurcations, undergo a strong variation as a function of small changes of electrical coupling. We found that there is a scaling law for the bifurcations of the limit cycles as a function of the strength of both couplings. From the functional point of view of this mixed typed of coupling, the small variation of electrical coupling provides a high sensitivity for period regulation inside the regime of out-of-phase synchronization.

Modulation of Oscillator Interactions in the Crab Stomatogastric Ganglion by Crustacean Cardioactive Peptide

The modulation of the pyloric rhythm of the stomatogastric ganglion of the crab, Cancer borealis, by crustacean cardioactive peptide (CCAP) is described. CCAP activated pyloric rhythms in most silent preparations, and altered the phase relationships of pyloric motor neuron firing in all preparations. In CCAP, the pyloric rhythms were characterized by long lateral pyloric (LP) neuron bursts of action potentials. The threshold for CCAP action was approximately 10(-10) M, with increasing effects at higher CCAP concentrations. The changes in motor pattern evoked by CCAP produced significant changes in LP-innervated muscle movement. These movements were additionally potentiated by CCAP applications to isolated nerve-muscle preparations. Thus, enhanced motor neuron firing and increase of the gain of the neuromuscular junctions are likely to operate coordinately in response to hormonally released CCAP. High CCAP concentrations sometimes resulted in modification of the normal 1:1 alternation between the pyloric dilator (PD) and LP neurons to patterns of 2:1, 3:1, or 4:1 alternation. CCAP seems to activate slow intrinsic oscillations in the LP neuron, as well as enhance faster oscillations in the pacemaker group of PD/anterior burster (AB) neurons. Simulations of fast and slow oscillators with reciprocal inhibitory coupling suggest mechanisms that could account for the mode switch from 1:1 alternation to multiple PD bursts alternating with one LP neuron burst.

Rhythmogenesis in single cells and population models: olfactory bulb and hippocampus

Dynamics of single cells, small networks and large cell populations are the subject of investigation. The generation and propagation of action potentials in the two major cell types of the olfactory bulb, i.e. in the mitral and granule cells, are simulated by multi-compartmental modeling techniques. The specific effects of the individual ionic currents, the propagation of the signals through the compartments, and dynamic phenomena occurring in small networks (such as synchronized oscillation due to excitatory and inhibitory coupling) have been demonstrated. A statistical model is given to describe the electrical activity patterns of large neural populations. The model is applied for describing the CA3 region of the hippocampus by incorporating some basic electrophysiological properties of hippocampal pyramidal and inhibitory neurons. Population activities as well as underlying single cell voltages are simulated during population bursts in the model of disinhibited hippocampal CA3 slice.

Self-regularization of chaos in neural systems: experimental and theoretical results

The results of neurobiological studies in both vertebrates and invertebrates lead to the general question: How is a population of neurons, whose individual activity is chaotic and uncorrelated able to form functional circuits with regular and stable behavior? What are the circumstances which support these regular oscillations? What are the mechanisms that promote this transition? We address these questions using our experimental and modeling studies describing the behavior of groups of spiking-bursting neurons. We show that the role of inhibitory synaptic coupling between neurons is crucial in the self-control of chaos.

Signal generation and propagation in the olfactory bulb: Multicompartmental modeling

The generation and propagation of action potentials in the two major cell types of the olfactory bulb, i.e., in the mitral and granule cells, are simulated by applying the multicompartmental modeling technique. The specific effects of the individual ionic currents, the propagation of the signals through the compartments, and several dynamic phenomena occurring in small networks (such as synchronized oscillation due to excitatory and inhibitory coupling) have been demonstrated.

MULTICOMPARTMENTAL MODELING OF THE OLFACTORY BULB

The generation and propagation of action potentials in the two major cell types of the olfactory bulb the mitral and granule cells are simulated by applying the multicompartmental modeling technique The specific effects of the individual ionic currents the propagation of the signals through the compartments and several dynamic phenomena occurring in small networks such as synchronized oscillation due to excitatory and inhibitory coupling have been demonstrated

Synchronized action of synaptically coupled chaotic model neurons.

Experimental observations of the intracellular recorded electrical activity in individual neurons show that the temporal behavior is often chaotic. We discuss both our own observations on a cell from the stomatogastric central pattern generator of lobster and earlier observations in other cells. In this paper we work with models with chaotic neurons, building on models by Hindmarsh and Rose for bursting, spiking activity in neurons. The key feature of these simplified models of neurons is the presence of coupled slow and fast subsystems. We analyze the model neurons using the same tools employed in the analysis of our experimental data. We couple two model neurons both electrotonically and electrochemically in inhibitory and excitatory fashions. In each of these cases, we demonstrate that the model neurons can synchronize in phase and out of phase depending on the strength of the coupling. For normal synaptic coupling, we have a time delay between the action of one neuron and the response of the other. We also analyze how the synchronization depends on this delay. A rich spectrum of synchronized behaviors is possible for electrically coupled neurons and for inhibitory coupling between neurons. In synchronous neurons one typically sees chaotic motion of the coupled neurons. Excitatory coupling produces essentially periodic voltage trajectories, which are also synchronized. We display and discuss these synchronized behaviors using two "distance" measures of the synchronization.

Partial synchronization in populations of pulse-coupled oscillators.

I study the long-term behavior of populations of nonlinear oscillators with all-to-all, noninstantaneous, pulse coupling. With fast enough excitatory coupling both the fully synchronized and the asynchronous state are unstable. In this case individual units fire quasiperiodically even though the network as a whole shows a periodic firing pattern. The behavior of networks with three or more units is different in this regard from that of two-unit networks. With inhibitory coupling the network can break up into a variable number of fully synchronized clusters. For fast inhibition the number of clusters tends to be large, while the number of clusters is smaller for slow inhibition. \textcopyright{} 1996 The American Physical Society.

Inhibition of renin secretion by Ca2+ through activation of myosin light chain kinase.

This study sought to identify specific enzyme(s) involved in the biochemical cascade of inhibition of renin secretion through Ca(2+)-calmodulin mediation with the use of inhibitors of protein kinase and phosphatases. Inhibition of renin secretion mediated by Ca(2+)-calmodulin was induced by incubating rat renal cortical slices in K(+)-rich depolarizing medium, producing > 50% inhibition. This inhibition was completely blocked by the calmodulin antagonist calmidazolium. The inhibitor of protein kinase with broad specificity, K-252a, blocked the inhibition of renin secretion. Neither KN-62, a specific inhibitor of Ca(2+)-calmodulin-dependent protein kinase II (CaMK II), nor specific inhibitors of protein phosphatase 2B (PP2B), cyclosporin A and FK-506, blocked the inhibition. On the other hand, all four known inhibitors specific for myosin light chain kinase (MLCK), with different chemical structures and mechanisms of inhibition (ML-9, ML-7, KT-5926 and wortmannin), almost completely protected renin secretion against the inhibition by Ca2+. In particular, ML-9 reversively protected > 77% secretion against the inhibition both in K(+)-rich medium alone and in combination with the calcium ionophore A-23187 in a concentration-dependent manner. Together, these findings from our present study provide the first evidence, albeit indirect in nature, for the possibility that activation of Ca(2+)-calmodulin-dependent MLCK at the downstream of Ca2+ influx into juxtaglomerular (JG) cells leads to phosphorylation of 20-kDa regulatory myosin light chain (MLC20). Through interaction with actin, the phosphorylated MLC20 may play an important role in the inhibitory stimulus-secretion coupling of renin.

Analysis of gamma rhythms in the rat hippocampus in vitro and in vivo.

1. We have shown previously, with experimental and computer models, how a '40 Hz' (gamma) oscillation can arise in networks of hippocampal interneurones, involving mutual GABAA-mediated synaptic inhibition and a source of tonic excitatory input. Here, we explore implications of this model for some hippocampal network phenomena in the rat in vitro and in vivo. 2. A model network was constructed of 1024 CA3 pyramidal cells and 256 interneurones. AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid), NMDA (N-methyl-D-aspartate), GABAA and GABAB receptors were simulated on pyramidal cells and on interneurones. 3. In both model and experiment, the frequency of network oscillations, in the gamma range, depended upon three parameters: GABAA conductance and decay time constant in interneurone-->interneurone connections, and the driving current to the interneurones. 4. The model of gamma rhythm predicts an average zero phase lag between firing of pyramidal cells and interneurones, as observed in the rat hippocampus in vivo. The model also reproduces a gamma rhythm whose frequency changes with time, at theta frequency (about 5 Hz). This occurs when there is 5 Hz modulation of a tonic signal to chandelier and basket cells. 5. Synchronized bursts can be produced in the model by several means, including partial blockade of GABAA receptors or of AMPA receptors on interneurones, or by augmenting AMPA-mediated EPSCs. In all of these cases, the burst can be followed by a 'tail' of transiently occurring gamma waves, a phenomenon observed in the hippocampus in vivo following sharp waves. This tail occurs in the model because of delayed excitation of the interneurones by the synchronized burst. A tail of gamma activity was found after synchronized epileptiform bursts both in the hippocampal slice (CA3 region) and in vivo. 6. Our data suggest that gamma-frequency EEG activity arises in the hippocampus when pools of interneurones receive a tonic or slowly varying excitation. The frequency of the oscillation depends upon the strength of this excitation and on the parameters regulating the inhibitory coupling between the interneurones. The interneurone network output is then imposed upon pyramidal neurones in the form of rhythmic synchronized IPSPs.

Neuropeptide Y suppresses prolactin secretion from rat anterior pituitary cells: evidence for interactions with dopamine through inhibitory coupling to calcium entry

Neuropeptide Y suppresses prolactin secretion from rat anterior pituitary cells: evidence for interactions with dopamine through inhibitory coupling to calcium entry

Neuropeptide Y suppresses prolactin secretion from rat anterior pituitary cells: evidence for interactions with dopamine through inhibitory coupling to calcium entry.

Expression of neuropeptide Y (NPY) in the medial basal hypothalamus is increased during lactation, and at least part of this increase is due to the appearance of the peptide in hypothalamic tuberoinfundibular dopamine neurons, a cell population that does not exhibit NPY expression in other physiological conditions. The present studies tested the hypothesis that NPY affects PRL secretion by modulating the action of dopamine (DA) at the lactotroph. In static incubations of cultured anterior pituitary (AP) cells, the addition of either NPY or DA in concentrations of 0.1-500 nM resulted in dose-dependent inhibition of PRL secretion, and the combination of DA and NPY in submaximal concentrations produced an additive inhibition of PRL release. NPY also inhibited PRL secretion induced by TRH in perifused AP cells, and the effects were again additive with DA. The interactions of NPY and DA on TRH-induced elevations in cytosolic Ca2+ ([Ca2+]i) were examined by loading cultured AP cells of lactating rats with the fluorescent calcium probe fura-2 TRH produced a dose-dependent stimulation of [Ca2+]i, which was characterized by a rapid transient spike and a more prolonged plateau. Both phases were attenuated by either DA or NPY at 100 nM and were nearly abolished by the combination of DA and NPY, whereas neither DA nor NPY altered resting [Ca2+]i. DA and NPY also inhibited the increases in PRL secretion and [Ca2+]i induced by elevated extracellular K+ in an additive manner. Stimulation of AP cells with TRH in the absence of extracellular Ca2+ resulted in an attenuated spike of PRL release and [Ca2+]i and no plateau phase. Under these conditions, DA still inhibited the residual [Ca2+]i and PRL responses, but the inhibitory effects of NPY on PRL secretion and [Ca2+]i, and the potentiation by NPY of DA inhibition, were abolished. These results suggest that one physiological function of the NPY expressed in tuberoinfundibular dopamine neurons in lactation is to amplify the inhibitory action of DA on PRL secretion through negative coupling to the Ca2+ messenger system, particularly the entry of extracellular Ca2+.

Synchronization induced by temporal delays in pulse-coupled oscillators.

We derive return maps and phase diagrams to identify mechanisms of synchronization of pulse-coupled oscillators and emphasize the importance of temporal delays and inhibitory coupling. Optimum synchronization between two oscillators is obtained for inhibitory coupling, where delays give rise to stable in-phase synchronization; those with excitatory coupling only synchronize with a phase lag. In large ensembles of globally coupled oscillators the delayed interaction leads to new collective phenomena like synchronization in multistable clusters of common phases for inhibitory coupling; for excitatory coupling a mechanism of emerging and decaying synchronized clusters prevails.

Role of G proteins and KCa channels in the muscarinic and beta-adrenergic regulation of airway smooth muscle

We have examined the functional consequences of G protein coupling to calcium-activated potassium (KCa) channels using isometric tension records from guinea pig tracheal smooth muscle. After incubation with 1 microgram/ml pertussis toxin (PTX) for 6 h, the contraction response to 1 microM methacholine (MCh) was suppressed by 31.7 +/- 5.0% (n = 10). Similarly, the contraction was inhibited by 29.1 +/- 5.0% (n = 6) after application of 0.1 microM AF-DX 116, an M2-selective muscarinic receptor antagonist. Cholera toxin (CTX, 2.0 micrograms/ml for 6 h), which activates the stimulatory G protein of adenylyl cyclase (Gs), also suppressed contraction by 43.9 +/- 3.3% (n = 11). The inhibitory effects of PTX, AF-DX 116, or CTX were reversed in the presence of 100 nM charybdotoxin (ChTX), a selective KCa channel inhibitor. These findings suggest that disruption of inhibitory coupling between muscarinic receptor and KCa channels mediated by PTX-sensitive G proteins, or KCa channel activation induced by Gs/adenylyl cyclase-linked processes, antagonizes muscarinic contraction. The isoproterenol concentration-inhibition curves for precontracted trachea (1 microM MCh) were shifted to the left after perfusion with PTX or AF-DX 116, and the leftward shift of the curve was blocked by ChTX. Thus direct or indirect regulation of KCa channels mediated by the inhibitory guanine nucleotide binding protein (Gi) and Gs may play a functionally important role in the mechanical antagonism by the two receptor agonists.

When inhibition not excitation synchronizes neural firing.

Excitatory and inhibitory synaptic coupling can have counter-intuitive effects on the synchronization of neuronal firing. While it might appear that excitatory coupling would lead to synchronization, we show that frequently inhibition rather than excitation synchronizes firing. We study two identical neurons described by integrate-and-fire models, general phase-coupled models or the Hodgkin-Huxley model with mutual, non-instantaneous excitatory or inhibitory synapses between them. We find that if the rise time of the synapse is longer than the duration of an action potential, inhibition not excitation leads to synchronized firing.

Sound localisation in crickets

Intracellular recordings were made from the auditory interneurons ON1, AN1 and AN2 in the prothoracic ganglion of the cricket Gryllus bimaculatus. Their responses to synthesized calling song (carrier frequency 5 kHz, intensity 40–90 dB SPL), presented monaurally and binaurally via legphones (acoustic trachea cut), were recorded (Fig. 2). These data were then analysed to determine the strength of inhibitory coupling of ON1-ON1, ON1-AN1 and ON1-AN2 (Fig. 3). Inhibitory coupling of ON1-ON1 and ON1-AN1 are relatively independent of stimulus intensity, ON1-ON1 = -0.25 to -0,4 ap ON1a/ap ON1b; ON1-AN1 = -0.4 to -0.55 ap AN1/ap ON1contra. The inhibition of AN2 by ON1 is rather ineffective, maximally -0.13ap AN2/ap ON1contra. The left-right contrast enhancement or gain, due to lateral inhibition via omega neurons, is 1.6–1.9 for the ON1 pair and 2–3.4 for the AN1 pair, over most of the relevant sound intensity range. For the AN2 pair, there is little contrast enhancement except at sound intensities > 80 dB SPL (Table 1).

Information processing of a complex system: Response behaviors specified by the Weierstrass function.

By generalizing the usual lateral neural inhibition, analytic behavior of the response function of a complex system is studied. Units of the system are assumed to be interconnected vertically by successive bifurcations and influenced horizontally by lateral inhibitory couplings. It is found that the response function is approximately expressed by the Weierstrass (W) function and the asymptotic behavior is specified by a power law. The exponent of the power law represents the fractal dimension determined by a geometrical structure of the interconnections and the lateral inhibitory couplings.

Inhibition-Produced Patterning in Chains of Coupled Nonlinear Oscillators

This paper describes the behavior of chains of oscillators in which there is both local coupling and coupling between points on the chain that are roughly a distance of a half-chain apart. The local coupling is designed to produce synchrony, while the long-distance coupling is an abstraction of inhibitory coupling: alone it would produce antiphase behavior between the oscillators directly coupled. The investigation is motivated by data concerning traveling waves of electrical activity in the nervous system of animals that swim in an undulatory manner and also by observations concerning the motor behavior of more general vertebrates in early development. The aim of the work is to show that this connectivity can give rise to waves with wavelength equal to the length of the chain, as observed in swimming animals, as well as the more complicated patterns seen in early development. The latter include “S-waves,” in which the two halves of the chain are each in synchrony but are oscillating in antiphase with one...

Clustering in globally coupled inhibitory neurons

A model of a large population of identical excitable neurons with a global slowly decaying inhibitory coupling is studied and its patterns of synchrony are examined. In addition to converging to a homogeneous fixed point and a homogeneous limit cycle, the system exhibits cluster states, in which it breaks spontaneously into a few macroscopically big clusters, each of which is fully synchronized. A method for calculating the stability of cluster states is described and used for investigating the dynamical behavior of the network versus the parameters that describe the neurons and synapses. Effects of stochastic noise on the network dynamics are discussed. At large enough noise the system goes to a globally stationary state. Low levels of noise preserve the cluster-like neuron trajectories. In the regime where a noiseless system converges to a fully synchronized periodic state, relatively low noise levels cause neurons to burst only every two or more consecutive time periods.

Influence of MgADP on phosphofructokinase from Escherichia coli. Elucidation of coupling interactions with both substrates.

A comprehensive assessment is presented of the mutual influence that MgADP, MgATP, and fructose 6-phosphate (Fru-6-P) have on each other's binding to phosphofructokinase (PFK) from E. coli. When virtually any combination of these ligands binds to PFK it produces a significant perturbation in the intrinsic tryptophan fluorescence intensity and/or polarization which not only provides a means to follow binding in titration experiments but which also underscores the fact that more than two different enzyme conformations result from the binding of these ligands. When MgATP is saturating, the binding of MgADP to the allosteric site increases the affinity the enzyme subsequently displays for Fru-6-P. However, in the absence of MgATP, MgADP can bind to both the allosteric site and the nucleotide portion of the active site, with the latter antagonizing the binding of Fru-6-P to an extent that leads to an overall inhibition of Fru-6-P binding by MgADP. MgADP binding at the allosteric site also inhibits the binding of MgATP, indicating that under many circumstances MgADP should be more properly viewed as an inhibitor rather than an activator of E. coli PFK. After quantifying all of the 20 dissociation constants and 11 coupling parameters between ligand pairs pertinent to this three-ligand system, the more significant coupling parameters have been further characterized by examining their variation with temperature to establish the apparent enthalpy and entropy contributions to the corresponding coupling free energies. For both activating and inhibitory couplings, the enthalpy and entropy terms have the same sign as the coupling free energy.(ABSTRACT TRUNCATED AT 250 WORDS)