SEARCH · PubMed Health

Results for “coupling”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 739 records · Page 41Linked to original sources

PubMed2006

Cardiovascular haemodynamics and ventriculo-arterial coupling in an acute pig model of coronary ischaemia-reperfusion.

Although reperfusion after coronary occlusion is mandatory for myocardial salvage, reperfusion may trigger a cascade of harmful events (reperfusion injury) adding to myocardial injury. We investigated effects of reperfusion on left ventricular (LV) haemodynamics and ventriculo-arterial (VA) coupling in pigs following acute myocardial ischaemia induced by coronary artery occlusion. Experiments were performed in six animals, with measurements of cardiac and arterial function at baseline, after 60 min of ischaemia (T60) and after 2 (T180) and 4 h of reperfusion (T300). Ventriculo-arterial coupling was assessed using the ventriculo-arterial elastance ratio of paper, as well as using a 'stiffness coupling' and 'temporal coupling' index. Reperfusion following ischaemia (T180 versus T60) induced a progressive decline in cardiovascular function, evidenced by a decrease in mean arterial blood pressure, cardiac output and ejection fraction which was not restored at T300. Although reperfusion also induced an increase in slope of the end-systolic pressure-volume relationship (ESPVR), the ESPVR curve shifted to the right, associated with a depression of contractile function. Histology demonstrated irreversible myocardial damage at T300. The ventriculo-arterial elastance ratio and the 'stiffness coupling' index were unaffected throughout the protocol, but the 'temporal coupling' parameter indicated a relative shift between heart period and the time constant of the arterial system. It is unlikely that these alterations are attributable to ischaemic injury alone. The combination of both the stiffness and temporal coupling index may provide more information when studying ventriculo-arterial coupling than the more commonly used ventricular end-systolic stiffness/effection arterial elastance (E(es)/E(a)) ratio.

Animals↗

PubMed1978

Electrical coupling and dye transfer between acinar cells in rat salivary glands.

1. Adjacent acinar cells in isolated rat parotid and submaxillary glands were found to be electrically coupled in greater than 90% of the pairs tested. 2. Cells injected with fluorescein or procion yellow showed transfer of the dyes to their coupled neighbours. While not all coupled cells exchanged dye, exchange occurred only between coupled cells. 3. In experiments using three micro-electrodes, coupled acinar cells from parotid gland were found to have a mean coupling coefficient of 0.69 +/- 0.04. This value is higher than those reported for most other vertebrate epithelial systems. 4. Membrane damage sufficient to reduce the occurrence of coupling between cells by 97% lowered the transmembrane potential by only 13%. This would indicate that in this system membrane potential may not be the most sensitive indicator of cell damage. 5. The significance of the presence of electrical coupling and cell-to-cell transfer of small tracer molecules is discussed in relation to salivary gland structure and possible functional consequences.

Acetylcholine↗

PubMed2002

Gating properties of GIRK channels activated by Galpha(o)- and Galpha(i)-coupled muscarinic m2 receptors in Xenopus oocytes: the role of receptor precoupling in RGS modulation.

'Regulators of G protein Signalling' (RGSs) accelerate the activation and deactivation kinetics of G protein-gated inwardly rectifying K(+) (GIRK) channels. In an apparent paradox, RGSs do not reduce steady-state GIRK current amplitudes as expected from the accelerated rate of deactivation when reconstituted in Xenopus oocytes. We present evidence here that this kinetic anomaly is dependent on the degree of G protein-coupled receptor (GPCR) precoupling, which varies with different Galpha(i/o)-RGS complexes. The gating properties of GIRK channels (Kir3.1/Kir3.2a) activated by muscarinic m2 receptors at varying levels of G protein expression were examined with or without the co-expression of either RGS4 or RGS7 in Xenopus oocytes. Different levels of specific m2 receptor-Galpha coupling were established by uncoupling endogenous pertussis toxin (PTX)-sensitive Galpha(i/o) subunits with PTX, while expressing varying amounts of a single PTX-insensitive subunit (Galpha(i1(C351G)), Galpha(i2(C352G)), Galpha(i3(C351G)), Galpha(oA(C351G)), or Galpha(oB(C351G))). Co-expression of each of the PTX-insensitive Galpha(i/o) subunits rescued acetylcholine (ACh)-elicited GIRK currents (I(K,ACh)) in a concentration-dependent manner, with Galpha(o) isoforms being more effective than Galpha(i) isoforms. Receptor-independent 'basal' GIRK currents (I(K,basal)) were reduced with increasing expression of PTX-insensitive Galpha subunits and were accompanied by a parallel rise in I(K,ACh). These effects together are indicative of increased Gbetagamma scavenging by the expressed Galpha subunit and the subsequent formation of functionally coupled m2 receptor-G protein heterotrimers (Galpha((GDP))betagamma). Co-expression of RGS4 accelerated all the PTX-insensitive Galpha(i/o)-coupled GIRK currents to a similar extent, yet reduced I(K,ACh) amplitudes 60-90 % under conditions of low Galpha(i/o) coupling. Kinetic analysis indicated the RGS4-dependent reduction in steady-state GIRK current was fully explained by the accelerated deactivation rate. Thus kinetic inconsistencies associated with RGS4-accelerated GIRK currents occur at a critical threshold of G protein coupling. In contrast to RGS4, RGS7 selectively accelerated Galpha(o)-coupled GIRK currents. Co-expression of Gbeta5, in addition to enhancing the kinetic effects of RGS7, caused a significant reduction (70-85 %) in steady-state GIRK currents indicating RGS7-Gbeta5 complexes disrupt Galpha(o) coupling. Altogether these results provide further evidence for a GPCR-Galphabetagamma-GIRK signalling complex that is revealed by the modulatory affects of RGS proteins on GIRK channel gating. Our functional experiments demonstrate that the formation of this signalling complex is markedly dependent on the concentration and composition of G protein-RGS complexes.

Acetylcholine↗

PubMedDate not supplied

Role of cellular orientation in electrical coupling between gastrointestinal smooth muscle.

Electrical fields produced during depolarization as well as low resistance pathways through gap junctions have been proposed as electrical coupling mechanisms serving to coordinate electrical control activity in gastrointestinal smooth muscle. The differing orientations of the longitudinal and circular muscle layers offer many possible configurations for cells coupled by electrical fields. The boundary element method is used to investigate coupling, with respect to both gap junctions and field effects for ellipsoidal and cylindrical cells. Physiological considerations allow the possibility of aggregates of cells with coordinated electrical activity. The effect of multiple source cells on field coupling is also modeled. Results indicate that even small gap junctional conductances are effective for coupling of smooth muscle and that field coupling is most efficacious when the ellipsoidal cells are coupled side by side and when cylindrical cells are coupled end to end.

Animals↗

PubMed2002

Coupled-mode sound propagation in a range-dependent, moving fluid.

Full-field acoustic methods for current velocity inversion require accurate and efficient mathematical models of sound propagation in a range-dependent waveguide with flow. In this paper, an exact coupled-mode representation of the acoustic field is derived. To account for the physics of the problem, normal modes in a corresponding range-independent waveguide are chosen as the local basis. In the absence of currents, mode shape functions form a complete orthogonal basis. This property is heavily used in coupled-mode theories of sound propagation in motionless fluid. Unlike in the motionless case, however, vertical dependencies of acoustic pressure in individual normal modes are not orthogonal in the presence of currents. To overcome this difficulty, linearized equations of hydrodynamics are rewritten in terms of a state vector. Its five components are expressed in terms of acoustic pressure and particle displacement due to the wave. Orthogonality of the state vectors corresponding to individual normal modes is established. Coupled differential equations are derived for range-dependent mode amplitudes, leading to a remarkably simple result. The mode-coupling equations have the same form as those known for the motionless case, but of course the values of the mode-coupling coefficients differ as long as the range dependence of the flow velocity contributes to mode coupling in addition to the range dependence of sound speed and fluid density. The mode-coupling formulation is verified against known coupled-mode equations for certain limiting cases and an exact analytic solution of a benchmark problem.

Humans↗

PubMed2006

A comparison of the antagonist affinities for the Gi- and Gs-coupled states of the human adenosine A1-receptor.

The antagonist affinity for a given receptor is traditionally considered to be constant, reflecting the chemical nature of the specific ligand-receptor interaction. However, recent observations with all three beta-adrenoceptors have cast doubt on this basic pharmacological principle. The extent to which this finding applies to other G protein-coupled receptors and their interaction with different G proteins is unknown. Therefore, we studied the influence of different agonists on antagonist affinity measurements for Gi- and Gs-coupled conformations of the adenosine A1-receptor in Chinese hamster ovary cells stably expressing the human adenosine A1-receptor and a cAMP-response element (CRE)-secreted placental alkaline phosphatase reporter gene. Gi-coupled inhibition of [3H]cAMP accumulation via the A1-receptor was observed at low concentrations of agonist; however, a small increase in [3H]cAMP accumulation was also seen at higher agonist concentrations. This biphasic response was more evident for A1-stimulated CRE-gene transcription. The inhibitory component was abolished by pretreatment with pertussis toxin, whereas the stimulatory component was augmented, suggesting that the responses were due to an A1-Gi-coupled inhibition followed by an A1-Gs-coupled stimulation. However, the antagonist affinity values measured at the Gi-coupled and Gs-coupled conformations of the receptor were the same in both functional responses and whole-cell binding. Thus, in marked contrast to the beta-adrenoceptors, the A1-receptor conforms to the long-held principle of pharmacology that antagonist affinity measurements are constant regardless of the response being measured and the competing agonist used to stimulate that response. This was true even when the receptor was shown, in the same assay, to exist in two different conformational states coupled to two different G proteins.

Adenosine A1 Receptor Antagonists↗

PubMed2000

Molecular analysis of beta(2)-adrenoceptor coupling to G(s)-, G(i)-, and G(q)-proteins.

The beta(2)-adrenoceptor (beta(2)AR) couples to the G-protein G(s) to activate adenylyl cyclase. Intriguingly, several studies have demonstrated that the beta(2)AR can also interact with G-proteins of the G(i)- and G(q)-family. To assess the efficiency of beta(2)AR interaction with various G-protein alpha-subunits (G(xalpha)), we expressed fusion proteins of the beta(2)AR with the long (G(salphaL)) and short (G(salphaS)) splice variants of G(salpha), the G(i)-proteins G(ialpha2) and G(ialpha3), and the G(q)-proteins G(qalpha) and G(16alpha) in Sf9 cells. Fusion proteins provide a rigorous approach for comparing the coupling of a given receptor to G(xalpha) because of the defined 1:1 stoichiometry of receptor and G-protein and the efficient coupling. Here, we show that the beta(2)AR couples to G(s)-, G(i)-, and G(q)-proteins as assessed by ternary complex formation and ligand-regulated guanosine 5'-O-(3-thiotriphosphate) (GTPgammaS) binding. The combined analysis of ternary complex formation, GTPgammaS binding, agonist efficacies, and agonist potencies revealed substantial differences in the interaction of the beta(2)AR with the various classes of G-proteins. Comparison of the coupling of the beta(2)AR and formyl peptide receptor to G(ialpha2) revealed receptor-specific differences in the kinetics of GTPgammaS binding. We also detected highly efficient stimulation of GTPgammaS dissociation from G(salphaL), but not from G(qalpha) and G(16alpha), by a beta(2)AR agonist. Moreover, we show that the 1:1 stoichiometry of receptor to G-protein in fusion proteins reflects the in vivo stoichiometry of receptor/G-protein coupling more closely than was previously assumed. Collectively, our data show 1) that the beta(2)AR couples differentially to G(s)-, G(i)-, and G(q)-proteins, 2) that there is ligand-specific coupling of the beta(2)AR to G-proteins, 3) that receptor-specific G-protein conformational states may exist, and 4) that nucleotide dissociation is an important mechanism for G-protein deactivation.

Adrenergic Agonists↗

PubMed2002

The intracellular loops of the GB2 subunit are crucial for G-protein coupling of the heteromeric gamma-aminobutyrate B receptor.

The gamma-aminobutyrate B (GABA(B)) receptor is the first discovered G-protein-coupled receptor (GPCR) that needs two subunits, GB1 and GB2, to form a functional receptor. The GB1 extracellular domain (ECD) binds GABA, and GB2 contains enough molecular determinants for G-protein activation. The precise role of the two subunits in G-protein coupling is investigated. GB1 and GB2 are structurally related to the metabotropic glutamate, Ca(2+)-sensing and other family 3 GPCRs in which the second (i2) as well as the third (i3) intracellular loop play important roles in G-protein coupling. Here, the role of the i2 loops of GB1 and GB2 in the GABA(B) receptor ability to activate G(alpha)-proteins is investigated. To that aim, the i2 loops were swapped between GB1 and GB2 heptahelical domains (HDs), either in the wild-type subunits or in the chimeric subunits GB1/2 that contain the ECD of GB1 and the HD of GB2. The effect of an additional mutation within the i3 loop of GB2 that prevents coupling of the heteromeric receptor was also examined. Combinations of interest were found to be correctly addressed at the cell surface and to assemble into heteromers. Taken together our data revealed the following new information on the G-protein coupling of the heteromeric GABA(B) receptor: 1) the i2 loop of GB2 within the GB2 HD is required for the heteromeric GABA(B) receptor to couple to G-proteins, whereas the i2 loop of GB1 is not; 2) the presence of the i2 loop of GB2 within the GB1 HD is not sufficient to allow coupling of GB1; 3) the GB2 HD activates the Gqi9 protein whether it is associated with the GB2 or GB1 ECD; 4) in the combination with two GB2 HDs, each is able to couple to G-proteins; and finally, 5) the use of mutations in i2, i3, or both within the GB2 HD brings evidence for the absence of domain swapping enabling the exchange of region including i2 and i3 between the subunits.

Amino Acid Sequence↗

PubMed1998

Efficiency and frequency of translational coupling between the bacteriophage T4 clamp loader genes.

The bacteriophage T4 DNA polymerase holoenzyme is composed of the core polymerase, gene product 43 (gp43), in association with the "sliding clamp" of the T4 system, gp45. Sliding clamps are the processivity factors of DNA replication systems. The T4 sliding clamp comes to encircle DNA via the "clamp loader" activity inherent in two other T4 proteins: 44 and 62. These proteins assemble into a pentameric complex with a precise 4:1 stoichiometry of proteins 44 and 62. Previous work established that T4 genes 44 and 62, which are directly adjacent on polycistronic mRNA molecules, are-to some degree-translationally coupled. In the present study, measurement of the levels (monomers/cell) of the clamp loader subunits during the course of various T4 infections in different host cell backgrounds was accomplished by quantitative immunoblotting. The efficiency of translational coupling was obtained by determining the in vivo levels of gp62 that were synthesized when its translation was either coupled to or uncoupled from the upstream translation of gene 44. Levels of gp44 were also measured to determine the relative stoichiometry of synthesis and the percentage of gp44 translation that was transmitted across the intercistronic junction (coupling frequency). The results indicated a coupling efficiency of approximately 85% and a coupling frequency of approximately 25% between the 44-62 gene pair during the course of infection. Thus, translational coupling is the major factor in maintaining the 4:1 stoichiometry of synthesis of the clamp loader subunits. However, coupling does not appear to be an absolute requirement for the synthesis of gp62.

Bacteriophage T4↗

PubMed1995

Antenatal screening for carriers of cystic fibrosis: randomised trial of stepwise v couple screening.

OBJECTIVE: To perform a rigorous comparative evaluation of stepwise and couple approaches to antenatal carrier screening for cystic fibrosis. DESIGN: Pragmatic randomised trial. SETTING: Hospital antenatal clinic serving a regional population. SUBJECTS: 2002 women (couples) attending for booking antenatal visit at less than 17 weeks' gestation with no family history of cystic fibrosis. INTERVENTIONS: Offering counselling and carrier testing for cystic fibrosis, either to women in the first instance (stepwise) or to couples (couple screening). MAIN OUTCOME MEASURES: Uptake rates; anxiety; knowledge of cystic fibrosis and carrier status (both partners); attitudes to health, pregnancy, the baby, and screening (both partners); and uptake of carrier testing by relatives. RESULTS: Uptake of screening was the same for both approaches (90%). After delivery most women remembered test results and their meaning, but 53/253 (21%) of those with negative results of couple testing had forgotten that repeat testing would be advisable if they had a pregnancy with a new partner. With stepwise screening women identified as carriers had high levels of anxiety when results were received (mean anxiety score 52.3). This dissipated with a reassuring partner's result (carriers' mean anxiety score 36.1) to levels similar to those receiving negative results from couple screening. Of those receiving negative results, women who had stepwise screening were significantly less anxious than those who had couple screening (mean score with result 32.1 v 35.4, 95% confidence interval for difference -4.7 to -2.1). CONCLUSIONS: Couple screening allows carriers to avoid transient high levels of anxiety, but is associated with more anxiety and false reassurance among most screenees who will test negative. Stepwise screening gives carriers and their relatives genetic information and is, in our opinion, the better method.

Anxiety↗

PubMed2003

Estimating the costs and benefits of screening monogamous, heterosexual couples for unrecognised infection with herpes simplex virus type 2.

OBJECTIVES: Herpes simplex virus type 2 (HSV-2) is the most common cause of ulcerative genital disease in the United States, but infection is commonly unrecognised. Serological screening tests could identify discordantly infected couples and permit targeted interventions to limit HSV-2 transmission. Our objective was to evaluate the projected cost effectiveness of strategies to prevent HSV-2 transmission in couples with no history of HSV-2 infection. METHODS: We created a mathematical model to simulate the natural history and costs of HSV-2 transmission, and the expected impact of HSV-2 prevention strategies in monogamous, heterosexual couples. Strategies evaluated included (i) no screening; (ii) universal condom use; and (iii) serological screening for HSV-2 with condom use targeted to discordant couples. Screening tests considered included western blot (WB), ELISA, and ELISA with confirmation of positive test results using WB (ELISA-->WB). RESULTS: Compared to no screening, the use of ELISA-->WB prevented 38 future infections per 1000 couples, with a cost effectiveness ratio of $8200 per infection averted. The use of WB in all couples had an incremental cost effectiveness ratio of $63 600 per infection averted. Strategies of ELISA alone and universal condom use were not cost effective. The cost effectiveness of ELISA-->WB improved with increasing prevalence of HSV-2, but worsened with decreasing condom compliance. Screening with ELISA alone was a reasonable strategy only when ELISA specificity increased to 99%. CONCLUSIONS: Serological screening for unrecognised HSV-2 infection in monogamous, heterosexual couples is expected to decrease the incidence of HSV-2 infection, but increase healthcare costs. For couples choosing to be screened, a two step testing strategy (ELISA-->WB) is recommended. Recommendations for a national policy to conduct serological screening will depend on the value placed on averting an incident HSV-2 infection.

Blotting, Western↗

PubMed1997

GTP gammaS removal of D-600 block of skeletal muscle excitation-contraction coupling.

G proteins interacting with dihydropyridine receptors (DHPR) in transverse tubules (TT) of skeletal muscle may have a role in skeletal excitation-contraction (EC) coupling. The aim of this study was to determine the effects of G protein-specific nucleotides [guanosine 5'-O-(3-thiotriphosphate) (GTP gammaS) and guanosine 5'-O-(2-thiodiphosphate) (GDP betaS)] on the EC coupling mechanism in the presence of D-600, an agent that blocks EC coupling by immobilizing the voltage-sensing subunit of the DHPR in its inactivated state. By use of the mechanically peeled single-fiber preparation from rabbit adductor magnus skeletal muscle, 50 microM GTP gammaS and 500 microM GDP betaS were applied with the fiber in a D-600-induced state of blocked EC coupling. Neither nucleotide served as an independent stimulus for sarcoplasmic reticulum (SR) Ca2+ release when added to the TT polarizing bath under conditions of D-600 block. The presence of GTP gammaS or GDP betaS during a complete EC coupling cycle removed the D-600 block of EC coupling, despite continuous bath D-600. After the nucleotides were washed out, in the continued presence of D-600, the D-600 block of EC coupling was reestablished. In contrast, GTP gammaS added only during the period of TT depolarization under D-600 block did not remove the D-600 block of EC coupling, even though GTP gammaS did stimulate SR Ca2+ release. GTP gammaS had no effect on submaximum (0.5-1.0 mM) caffeine contractures and thus is unlikely to be acting through the Ca2+-induced Ca2+ release mechanism of the SR. These data suggest that the molecular binding site for GTP gammaS and GDP betaS is likely to be in the TT near the DHPR, perhaps on a G protein.

Animals↗

PubMed1990

Coupling mechanisms in airway smooth muscle.

This review documents available information about coupling mechanisms involved in airway smooth muscle force development and maintenance and relaxation of force. Basic concepts, obtained from experiments performed on many different mammalian cell types, are in place regarding coupling between surface membrane receptors and cell function; these concepts are considered as a framework for understanding coupling between receptors and contractile proteins in smooth muscles and in airway smooth muscles. We have divided various components of coupling mechanisms into those dependent on changes in the surface membrane potential (electromechanical coupling) and those independent of the surface membrane potential (pharmacomechanical coupling). We have, to some degree, emphasized modulation of coupling mechanisms by intrasurface membrane microprocessing or by second messengers. A challenge for the future is to obtain a better understanding of how coupling mechanisms are altered or modulated during different phases of contractions evoked by a single agonist and under conditions of multiple agonist exposure to airway smooth muscle cells.

Animals↗

PubMed2005

Computational model of electrically coupled, intrinsically distinct pacemaker neurons.

Electrical coupling between neurons with similar properties is often studied. Nonetheless, the role of electrical coupling between neurons with widely different intrinsic properties also occurs, but is less well understood. Inspired by the pacemaker group of the crustacean pyloric network, we developed a multicompartment, conductance-based model of a small network of intrinsically distinct, electrically coupled neurons. In the pyloric network, a small intrinsically bursting neuron, through gap junctions, drives 2 larger, tonically spiking neurons to reliably burst in-phase with it. Each model neuron has 2 compartments, one responsible for spike generation and the other for producing a slow, large-amplitude oscillation. We illustrate how these compartments interact and determine the dynamics of the model neurons. Our model captures the dynamic oscillation range measured from the isolated and coupled biological neurons. At the network level, we explore the range of coupling strengths for which synchronous bursting oscillations are possible. The spatial segregation of ionic currents significantly enhances the ability of the 2 neurons to burst synchronously, and the oscillation range of the model pacemaker network depends not only on the strength of the electrical synapse but also on the identity of the neuron receiving inputs. We also compare the activity of the electrically coupled, distinct neurons with that of a network of coupled identical bursting neurons. For small to moderate coupling strengths, the network of identical elements, when receiving asymmetrical inputs, can have a smaller dynamic range of oscillation than that of its constituent neurons in isolation.

Animals↗

PubMed2002

Electrical coupling between model midbrain dopamine neurons: effects on firing pattern and synchrony.

The role of gap junctions between midbrain dopamine (DA) neurons in mechanisms of firing pattern generation and synchronization has not been well characterized experimentally. We modified a multi-compartment model of DA neuron by adding a spike-generating mechanism and electrically coupling the dendrites of two such neurons through gap junctions. The burst-generating mechanism in the model neuron results from the interaction of a N-methyl-D-aspartate (NMDA)-induced current and the sodium pump. The firing patterns exhibited by the two model neurons included low frequency (2-7 Hz) spiking, high-frequency (13-20 Hz) spiking, irregular spiking, regular bursting, irregular bursting, and leader/follower bursting, depending on the parameter values used for the permeability for NMDA-induced current and the conductance for electrical coupling. All of these firing patterns have been observed in physiological neurons, but a systematic dependence of the firing pattern on the covariation of these two parameters has not been established experimentally. Our simulations indicate that electrical coupling facilitates NMDA-induced burst firing via two mechanisms. The first can be observed in a pair of identical cells. At low frequencies (low NMDA), as coupling strength was increased, only a transition from asynchronous to synchronous single-spike firing was observed. At high frequencies (high NMDA), increasing the strength of the electrical coupling in an identical pair resulted in a transition from high-frequency single-spike firing to burst firing, and further increases led to synchronous high-frequency spiking. Weak electrical coupling destabilizes the synchronous solution of the fast spiking subsystems, and in the presence of a slowly varying sodium concentration, the desynchronized spiking solution leads to bursts that are approximately in phase with spikes that are not in phase. Thus this transitional mechanism depends critically on action potential dynamics. The second mechanism for the induction of burst firing requires a heterogeneous pair that is, respectively, too depolarized and too hyperpolarized to burst. The net effect of the coupling is to bias at least one cell into an endogenously burst firing regime. In this case, action potential dynamics are not critical to the transitional mechanism. If electrical coupling is indeed more prominent in vivo due to basal level of modulation of gap junctions in vivo, these results may indicate why NMDA-induced burst firing is easier to observe in vivo as compared in vitro.

Action Potentials↗

PubMed2002

Electrical coupling can prevent expression of adult-like properties in an embryonic neural circuit.

Electrical coupling is widespread in developing nervous systems and plays a major role in circuit formation and patterning of activity. In most reported cases, such coupling between rhythmogenic neurons tends to synchronize and enhance their oscillatory behavior, thereby producing monophasic rhythmic output. However, in many adult networks, such as those responsible for rhythmic motor behavior, oscillatory neurons are linked by synaptic inhibition to produce rhythmic output with multiple phases. The question then arises whether such networks are still able to generate multiphasic output in the early stage of development when electrical coupling is abundant. A suitable model for addressing this issue is the lobster stomatogastric nervous system (STNS). In the adult animal, the STNS consists of three discrete neural networks that are comprised of oscillatory neurons interconnected by reciprocal inhibition. These networks generate three distinct rhythmic motor patterns with large amplitude neuronal oscillations. By contrast, in the embryo the same neuronal population expresses a single multiphasic rhythm with small-amplitude oscillations. Recent findings have revealed that adult-like network properties are already present early in the embryonic system but are masked by an as yet unknown mechanism. Here we use computer simulation to test whether extensive electrical coupling may be involved in masking adult-like properties in the embryonic STNS. Our basic model consists of three different adult-like STNS networks that are built of relaxation oscillators interconnected by reciprocal synaptic inhibition. Individual model cells generate slow membrane potential oscillations without action potentials. The introduction of widespread electrical coupling between members of these networks dampens oscillation amplitudes and, at moderate coupling strengths, may coordinate neuronal activity into a single rhythm with different phases, which is strongly reminiscent of embryonic STNS output. With a further increase in coupling strength, the system reaches one of two final states depending on the relative contribution of inhibition and inherent oscillatory properties within the networks: either fully synchronized and dampened oscillations, or a complete collapse of activity. Our simulations indicate that, beginning from either of these two states, the emergence of distinct adult networks during maturation may arise from a developmental decrease in electrical coupling that unmasks preexisting adult-like network properties.

Action Potentials↗

PubMed1985

Intersegmental coordination of the leech swimming rhythm. I. Roles of cycle period gradient and coupling strength.

The isolated leech nervous system generates a metachronally coordinated rhythmic output that is the neuronal correlate of swimming activity. We investigated two factors that contribute to intersegmental coordination: the swim-cycle periods expressed by segmental ganglia and the strength of neuronal coupling between ganglia. To determine the regional variation in swim-cycle periods, we severed both of the lateral intersegmental connectives. We left intact the median connective, which conveys tonic excitation but little phasic information. We obtained a reduction in intersegmental coupling strength by severing a single lateral intersegmental connective. Cycle periods were manipulated by cooling restricted sections of the nerve cord. Our experiments revealed an anterior-posterior gradient of cycle periods in ganglia of the isolated nerve cord; that is, chains of ganglia obtained from the anterior nerve cord exhibited longer cycle periods than those obtained from the posterior end of the cord. This gradient extends posteriorly to approximately ganglion 12 and may reverse posterior to ganglion 13. Increasing local cycle periods by cooling restricted sections of the nerve cord caused delay in activity cycles in the cooled ganglia, relative to the cycles of ganglia at the control temperature. This finding demonstrates that the observed gradient in cycle period provides for smaller intersegmental phase lags than would occur if there were no period gradients. Reduction of coupling strength by severing a lateral connective led to altered phase relationships across the lesion, both at the motor and oscillator levels. For those ganglion chains in which the anterior ganglia had greater periods, the reduced coupling led to reduced or even reversed phase relationships across the lesion but left unchanged the phase lag between the ends of the chain. In contrast, reduced coupling between halves of a chain in which the posterior ganglia had greater cycle periods led to increased phase lags across the lesion and between the ends. These altered phase relationships arise from a relative increase in the contribution of period differences when coupling strength is decreased. We conclude that the anterior-to-posterior progression of neuronal activity in the isolated leech nerve cord during swimming activity is provided by the intersegmental coupling signals. Furthermore, the period gradient expressed in our preparations acts to provide for smaller phase lags than would be generated by these coupling signals in the absence of such a gradient.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1995

Structural basis of cortical synchronization. I. Three types of interhemispheric coupling.

1. Single-unit and multiunit activities were recorded at the area 17-18 border of each cortical hemisphere in paralyzed cats anesthetized with nitrous oxide supplemented with halothane. Cross-correlation histograms (CCHs) were computed between 86 pairs of single units and 99 pairs of multiunit activities. Visually evoked peaks in the CCHs were removed by subtracting the shift predictor. 2. Three types of CCH peaks were observed: T peaks with narrow widths (4-28 ms), C peaks with intermediate widths (30-100 ms), and H peaks with large widths (100-1,000 ms). Oscillatory coupling was observed rarely. This tripartite distribution of CCH peaks is similar to that reported in an earlier study on the temporal coupling between areas 17 and 18. Different types of peaks occurred in isolation or in combination. Combination of different peak types was more often observed in multiunit recordings. 3. CCH peaks of all types were usually centered, meaning that units in opposite hemispheres tend to synchronize their discharges. 4. T peaks were observed almost exclusively for units with overlapping receptive fields and preferentially for units with similar optimal orientations. No dependence on receptive field position or optimal orientation was observed for the encounter rate of C and H peaks. 5. A new method, called the peristimulus CCH, was developed to study the time course of the temporal coupling. This showed that H peaks can occur during visual stimulation and that their time course follows that of the visual responses of the coupled neurons. 6. Using one single bar or two simultaneously presented light bars as stimuli, we studied the effect of visual stimulation on the strength of H coupling. This showed that H coupling observed under stimulation with a single moving light bar can be completely abolished, with little change in visual responses, when the stimulus is changed to two noncoherently moving bars. This was related to a strong decrease of the H peaks in the autocorrelograms. 7. These results demonstrate that T, C, and H peaks constitute, together with high-frequency oscillations, universal forms of temporal coupling between neurons located in different cortical areas. The following paper reports on the effects of cortical lesions on the encounter rate and strength of these different types of coupling.

Anesthesia↗