Dopamine maintains network synchrony via direct modulation of gap junctions in the crustacean cardiac ganglion

The Large Cell (LC) motor neurons of the crab cardiac ganglion have variable membrane conductance magnitudes even within the same individual, yet produce identical synchronized activity in the intact network. In a previous study we blocked a subset of K+ conductances across LCs, resulting in loss of synchronous activity (Lane et al., 2016). In this study, we hypothesized that this same variability of conductances makes LCs vulnerable to desynchronization during neuromodulation. We exposed the LCs to serotonin (5HT) and dopamine (DA) while recording simultaneously from multiple LCs. Both amines had distinct excitatory effects on LC output, but only 5HT caused desynchronized output. We further determined that DA rapidly increased gap junctional conductance. Co-application of both amines induced 5HT-like output, but waveforms remained synchronized. Furthermore, DA prevented desynchronization induced by the K+ channel blocker tetraethylammonium (TEA), suggesting that dopaminergic modulation of electrical coupling plays a protective role in maintaining network synchrony.

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Dopamine maintains network synchrony via direct modulation of gap junctions in the crustacean cardiac ganglion

10.1101/355651 ◽

2018 ◽

Author(s):

Brian J Lane ◽

Daniel R Kick ◽

David K Wilson ◽

Satish S Nair ◽

David J Schulz

Keyword(s):

Motor Neurons ◽

Channel Blocker ◽

Electrical Coupling ◽

Membrane Conductance ◽

Large Cell ◽

Protective Role ◽

Cardiac Ganglion ◽

Junctional Conductance ◽

Network Synchrony ◽

Gap Junctional

AbstractAbstract The Large Cell (LC) motor neurons of the crab (C. borealis) cardiac ganglion have variable membrane conductance magnitudes even within the same individual, yet produce identical synchronized activity in the intact network. In our previous study (Lane et al., 2016) we blocked a subset of K+ conductances across LCs, resulting in loss of synchronous activity. In this study, we hypothesized that this same variability of conductances could make LCs vulnerable to desynchronization during neuromodulation. We exposed the LCs to serotonin (5HT) and dopamine (DA) while recording simultaneously from multiple LCs. Both amines had distinct excitatory effects on LC output, but only 5HT caused desynchronized output. We further determined that DA rapidly increased gap junctional conductance. Co-application of both amines induced 5HT-like output, but waveforms remained synchronized. Furthermore, DA prevented desynchronization induced by the K+ channel blocker tetraethylammonium (TEA), suggesting that dopaminergic modulation of electrical coupling plays a protective role in maintaining network synchrony.

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Synergistic plasticity of intrinsic conductance and electrical coupling restores synchrony in an intact motor network

eLife ◽

10.7554/elife.16879 ◽

2016 ◽

Vol 5 ◽

Cited By ~ 14

Author(s):

Brian J Lane ◽

Pranit Samarth ◽

Joseph L Ransdell ◽

Satish S Nair ◽

David J Schulz

Keyword(s):

Motor Neurons ◽

Electrical Coupling ◽

High Threshold ◽

Cardiac Ganglion ◽

Physiological Regulation ◽

Blocking High ◽

Motor Network ◽

Ionic Conductances ◽

Network Output ◽

Coupling Conductance

Motor neurons of the crustacean cardiac ganglion generate virtually identical, synchronized output despite the fact that each neuron uses distinct conductance magnitudes. As a result of this variability, manipulations that target ionic conductances have distinct effects on neurons within the same ganglion, disrupting synchronized motor neuron output that is necessary for proper cardiac function. We hypothesized that robustness in network output is accomplished via plasticity that counters such destabilizing influences. By blocking high-threshold K+ conductances in motor neurons within the ongoing cardiac network, we discovered that compensation both resynchronized the network and helped restore excitability. Using model findings to guide experimentation, we determined that compensatory increases of both GA and electrical coupling restored function in the network. This is one of the first direct demonstrations of the physiological regulation of coupling conductance in a compensatory context, and of synergistic plasticity across cell- and network-level mechanisms in the restoration of output.

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Gap-junctional properties of electrically coupled skate horizontal cells in culture

Visual Neuroscience ◽

10.1017/s0952523800003680 ◽

1993 ◽

Vol 10 (2) ◽

pp. 287-295 ◽

Cited By ~ 25

Author(s):

Haohua Qian ◽

Robert Paul Malchow ◽

Harris Ripps

Keyword(s):

Receptive Field ◽

Lucifer Yellow ◽

Horizontal Cell ◽

Electrical Coupling ◽

Cell Voltage ◽

Horizontal Cells ◽

Electrical Synapse ◽

Cell Coupling ◽

Junctional Conductance ◽

Gap Junctional

AbstractWhole-cell voltage-clamp recordings were used to examine the unusual pharmacological properties of the electrical coupling between rod-driven horizontal cells in skate retina as revealed previously by receptive-field measurements (Qian & Ripps, 1992). The junctional resistance was measured in electrically coupled cell pairs that had been enzymatically isolated and maintained in culture; the typical value was about 19.92 MΩ(n = 45), more than an order of magnitude lower than the nonjunctional membrane resistance. These data and the intercellular spread of the fluorescent dye Lucifer Yellow provide a good indication that skate horizontal cells are well coupled. The junctional conductance between cells was not modulated by the neurotransmitters dopamine (200 μM) or GABA (1 mM), nor was it affected by the membrane-permeable analogues of cAMP or cGMP, or the adenylate cyclase activator, forskolin. Although resistant to agents that have been reported to alter horizontal-cell coupling in cone-driven horizontal cells, the junctional conductance between paired horizontal cells of skate was greatly reduced by the application of 20 mM acetate, which is known to effectively reduce intracellular pH. Together with the results obtained in situ on the receptive-field properties of skate horizontal cells, these findings indicate that the gap-junctional properties of rod-driven horizontal cells of the skate are fundamentally different from those of cone-driven horizontal cells in other species. This raises the possibility that there is more than one class of electrical synapse on vertebrate horizontal cells.

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Xenopus oocyte K+ current. III. Phorbol esters and pH regulate current at gap junctions

AJP Cell Physiology ◽

10.1152/ajpcell.1990.259.5.c792 ◽

1990 ◽

Vol 259 (5) ◽

pp. C792-C800 ◽

Cited By ~ 44

Author(s):

L. J. Greenfield ◽

J. T. Hackett ◽

J. Linden

Keyword(s):

Gap Junctions ◽

Phorbol Esters ◽

Electrical Coupling ◽

Follicle Cell ◽

Follicle Cells ◽

Acid Ph ◽

Junctional Conductance ◽

K Current ◽

Gap Junctional ◽

K Currents

Xenopus follicles consist of a single large oocyte surrounded by a monolayer of follicle cells attached to the oocyte by gap junctions. Adenosine 3',5'-cyclic monophosphate (cAMP) activates an outward K+ current which is completely abolished if follicle cells are removed or if phorbol esters (which have been reported to reduce gap junctional conductance) are added. In this study we show that phorbol esters do not reduce cAMP levels in follicles and that acid pH, another known stimulus for reducing gap junctional conductance, mimics the action of phorbol esters to inhibit the cAMP-stimulated K+ current. We also examined electrical coupling between oocytes of pairs of follicles placed in physical contact (across 2 oocyte-follicle cell and 1 follicle cell-follicle cell gap junction). Phorbol esters and acid pH (5.5-6.5) decreased electrical coupling without eliciting a shunt current, since slope conductance of current-voltage curves recorded during voltage clamp was simultaneously decreased. Increasing cAMP, which has been reported to enhance gap junctional conductance in mammalian cells, increased slope conductance without decreasing electrical coupling between pairs of follicles. The data suggest that cAMP increases and phorbol esters and acid pH decrease K+ currents at least in part by effects on gap junctions. The effects of phorbol esters and acid pH to reduce electrical coupling between oocytes cannot be due to blockade of K+ channels, since such an action would increase electrical coupling (as verified by computer simulations). These findings are consistent with the idea that cAMP-activated K+ currents originate in follicle cells and are communicated to the oocyte via gap junctions.

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Optical measurement of cell-to-cell coupling in intact heart using subthreshold electrical stimulation

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2001.281.2.h533 ◽

2001 ◽

Vol 281 (2) ◽

pp. H533-H542 ◽

Cited By ~ 45

Author(s):

Fadi G. Akar ◽

Bradley J. Roth ◽

David S. Rosenbaum

Keyword(s):

Fiber Orientation ◽

Optical Measurement ◽

Critical Role ◽

Electrical Coupling ◽

Membrane Properties ◽

Cell Coupling ◽

Close Proximity ◽

Junctional Conductance ◽

Gap Junctional ◽

Intact Heart

Electrical coupling between myocytes plays a critical role in propagation, repolarization, and arrhythmias. On the basis of predictions from cable theory, we hypothesized that the cardiac space constant (λ) measured from the decay of subthreshold transmembrane potential (ST- V m) in space would provide an index of regional cell-to-cell coupling in the intact heart. With the use of voltage-sensitive dyes, the distribution of ST- V m was measured from hundreds of sites in close proximity to the site of subthreshold stimulation. λ was calculated from the exponential decay of ST- V min space. Consistent with known directional differences in axial resistance, the spatial distribution of ST- V mwas strongly dependent on fiber orientation, because λ was significantly ( P < 0.001) longer along (1.5 ± 0.1 mm) compared with across (0.8 ± 0.1 mm) fibers. There was a close linear relationship ( P < 0.001) between conduction velocity (CV) and λ along all fiber angles tested. Reducing gap junctional conductance by heptanol reversibly decreased CV and λ in parallel by ∼50%. In contrast, sodium channel blockade by flecainide slowed CV by 40% but had no effect on λ, reaffirming that λ was an index of passive but not active membrane properties. These data establish the feasibility of measuring λ as an index of cell-to-cell coupling in the intact heart, and indicate strong dependency of λ on fiber orientation and pharmacological alterations of gap junction conductance.

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Impulse Identification and Axon Mapping of the Nine Neurons in the Cardiac Ganglion of the Lobster Homarus Americanus

Journal of Experimental Biology ◽

10.1242/jeb.47.2.327 ◽

1967 ◽

Vol 47 (2) ◽

pp. 327-341

Author(s):

DANIEL K. HARTLINE

Keyword(s):

Large Cell ◽

Homarus Americanus ◽

Simultaneous Recording ◽

Small Cell ◽

Complete Analysis ◽

Cardiac Ganglion ◽

Cell Identification ◽

Cell Axon ◽

Synaptic Interactions ◽

Stimulation Of

1. Simultaneous recording from several pairs of electrodes placed along the ganglion and certain efferent nerves, during stimulation of other efferents, allows the course of antidromic impulses in each stimulated axon to be mapped. 2. These impulses disappear as they approach their somata, being incapable of invading them, a fact which permits identification of a particular efferent axon with a particular soma. 3. By these means the courses of all such efferent axons, and their corresponding somata, have been determined. These all belong to the five large cells. 4. The impulses from each such axon occurring during the spontaneous burst can be identified, as can impulses from each small cell. 5. Each large-cell axon appears to be inexcitable until it is a few mm from the soma. 6. If the axon branches within this inexcitable region, the branches tend to fire impulses independently. 7. The technique of cell identification opens the way to a more complete analysis of the ganglion's activity and the synaptic interactions which produce it.

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Electrically coupled pacemaker neurons respond differently to same physiological inputs and neurotransmitters

Journal of Neurophysiology ◽

10.1152/jn.1984.51.6.1362 ◽

1984 ◽

Vol 51 (6) ◽

pp. 1362-1374 ◽

Cited By ~ 85

Author(s):

E. Marder ◽

J. S. Eisen

Keyword(s):

Motor Neurons ◽

Slow Wave ◽

Lucifer Yellow ◽

Electrical Coupling ◽

Excitatory Postsynaptic Potential ◽

Panulirus Interruptus ◽

Bursting Neuron ◽

Postsynaptic Potential ◽

Pyloric Dilator ◽

Muscarinic Cholinergic

The two pyloric dilator (PD) motor neurons and the single anterior burster (AB) interneuron are electrically coupled and together comprise the pacemaker for the pyloric central pattern generator of the stomatogastric ganglion of the lobster, Panulirus interruptus. Previous work (31) has shown that the AB neuron is an endogenously bursting neuron, while the PD neuron is a conditional burster. In this paper the effects of physiological inputs and neurotransmitters on isolated PD neurons and AB neurons were studied using the lucifer yellow photoinactivation technique (33). Stimulation of the inferior ventricular nerve (IVN) fibers at high frequencies elicits a triphasic response in AB and PD neurons: a rapid excitatory postsynaptic potential (EPSP) followed by a slow inhibitory postsynaptic potential (IPSP), followed by an enhancement of the pacemaker slow-wave depolarizations. Photoinactivation experiments indicate that the enhancement of the slow wave is due primarily to actions of the IVN fibers on the PD neurons but not on the AB neuron. Bath-applied dopamine dramatically alters the motor output of the pyloric system. Photoinactivation experiments show that 10(-4) M dopamine increases the amplitude and frequency of the slow-wave depolarizations recorded in the AB neurons but hyperpolarizes and inhibits the PD neurons. Bath-applied serotonin increases the frequency and amplitude of the slow-wave depolarizations in the AB neuron but has no effect on PD neurons. Pilocarpine, a muscarinic cholinergic agonist, stimulates slow-wave depolarization production in both PD neurons and the AB neuron, but the waveform and frequency of the slow waves elicited are quite different. These results show that although the electrically coupled PD and AB neurons always depolarize synchronously and act together as the pacemaker for the pyloric system, they respond differently to a neuronal input and to several putative neuromodulators. Thus, despite electrical coupling sufficient to ensure synchronous activity, the PD and AB neurons can be modulated independently.

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