scholarly journals Dopamine Modulation of Two Delayed Rectifier Potassium Currents in a Small Neural Network

2005 ◽  
Vol 94 (4) ◽  
pp. 2888-2900 ◽  
Author(s):  
Matthias Gruhn ◽  
John Guckenheimer ◽  
Bruce Land ◽  
Ronald M. Harris-Warrick

Delayed rectifier potassium currents [ IK(V)] generate sustained, noninactivating outward currents with characteristic fast rates of activation and deactivation and play important roles in shaping spike frequency. The pyloric motor network in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus, is made up of one interneuron and 13 motor neurons of five different classes. Dopamine (DA) increases the firing frequencies of the anterior burster (AB), pyloric (PY), lateral pyloric (LP), and inferior cardiac (IC) neurons and decreases the firing frequencies of the pyloric dilator (PD) and ventricular dilator (VD) neurons. In all six types of pyloric neurons, IK(V) is small with respect to other K+ currents. It is made up of at least two TEA-sensitive components that show differential sensitivity to 4-aminopyridine and quinidine, and have differing thresholds of activation. One saturable component is activated at potentials above −25 mV, whereas the second component appears at more depolarized voltages and does not saturate at voltage steps up to +45 mV. The magnitude of the components varies among cell types but also shows considerable variation within a single type. A subset of PY neurons shows a marked enhancement in spike frequency with DA; DA evokes a pronounced reversible increase in IK(V) conductance of ≤30% in the PY neurons studied, and on average significantly increases both components of IK(V). The AB neuron also shows a reversible 20% increase in the steady state IK(V). DA had no effect on IK(V) in PD, LP, VD, and IC neurons. The physiological roles of these currents and their modulation by DA are discussed.

1984 ◽  
Vol 51 (6) ◽  
pp. 1362-1374 ◽  
Author(s):  
E. Marder ◽  
J. S. Eisen

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.


2002 ◽  
Vol 88 (6) ◽  
pp. 2942-2953 ◽  
Author(s):  
Muriel Thoby-Brisson ◽  
John Simmers

Rhythm generation by the pyloric motor network in the stomatogastric ganglion (STG) of the spiny lobster requires permissive neuromodulatory inputs from other central ganglia. When these inputs to the STG are suppressed by cutting the single, mainly afferent stomatogastric nerve (stn), pyloric neurons cease to burst and the network falls silent. However, as shown previously, if such a decentralized quiescent ganglion is maintained in organ culture, pyloric network rhythmicity returns after 3–4 days and, although slower, is similar to the motor pattern expressed when the stn is intact. Here we use current- and voltage-clamp, primarily of identified pyloric dilator (PD) neurons, to investigate changes in synaptic and cellular properties that underlie this transition in network behavior. Although the efficacy of chemical synapses between pyloric neurons decreases significantly (by ≤50%) after STG decentralization, the fundamental change leading to rhythm recovery occurs in the voltage-dependent properties of the neurons themselves. Whereas pyloric neurons, including the PD, lateral pyloric, and pyloric cell types, are unable to generate burst-producing membrane potential oscillations in the short-term absence of extrinsic modulatory inputs, in long-term decentralized ganglia, the same cells are able to oscillate spontaneously, even after experimental isolation in situ from all other elements in the pyloric network. In PD neurons this reacquisition of rhythmicity is associated with a net reduction in outward tetraethylammonium-sensitive ionic currents that include a delayed-rectifier type potassium current ( I Kd) and a calcium-dependent K+ current, I KCa. By contrast, long-term STG decentralization caused enhancement of a hyperpolarization-activated inward current that resembles I h. These results are consistent with the hypothesis that modulatory inputs sustain the modulation-dependent rhythmogenic character of the pyloric network by continuously regulating the balance of membrane conductances that underlie neuronal oscillation.


1984 ◽  
Vol 51 (6) ◽  
pp. 1345-1361 ◽  
Author(s):  
E. Marder ◽  
J. S. Eisen

The neurotransmitters mediating the synaptic interactions among the neurons of the pyloric system of the stomatogastric ganglion (STG) of the lobster, Panulirus interruptus, were examined using a combination of electrophysiological, pharmacological, and biochemical techniques. Iontophoretically applied L-glutamate inhibited all motor neurons of the pyloric system. This inhibitory response was blocked by low concentrations of picrotoxin but unaffected by atropine. The anterior burster (AB) interneuron, pyloric dilator (PD) motor neurons, and ventricular dilator (VD) motor neuron were depolarized and excited by iontophoretically applied acetylcholine (ACh). The lateral pyloric (LP) and pyloric (PY) constrictor motor neurons were inhibited by ACh and by the cholinergic agonist, carbachol. These inhibitory cholinergic responses were blocked by atropine but not by picrotoxin. The inhibitory postsynaptic potentials (IPSPs) evoked by the constrictor motor neurons were blocked by picrotoxin but not by atropine. Taken together with previously published data (15, 18), this suggests that the constrictor motor neurons release glutamate at both their excitatory neuromuscular junctions and their inhibitory intraganglionic junctions. The lucifer yellow photoinactivation technique (27) was used to study separately the neurotransmitters released by the electrically coupled PD and AB neurons. The AB-evoked IPSPs were blocked by picrotoxin but not by atropine. The PD-evoked IPSPs were blocked by atropine and other muscarinic antagonists but not by picrotoxin. Somata of PD neurons contained choline acetyltransferase (CAT) activity, but somata of AB neurons contained no detectable CAT activity. On the basis of the data in this paper and previously published data (17, 18), we conclude that the PD neurons release ACh at both their excitatory neuromuscular junctions and their inhibitory intraganglionic connections. Although the AB neuron is electrically coupled to the PD neurons, the AB neuron is not cholinergic. Glutamate is a likely transmitter candidate for the AB neuron. These data show that electrically coupled neurons can release different transmitters. Furthermore, these data show that an IPSP can be the result of the combined actions of two different neurotransmitters, each released from a different neuron. The functional consequences of these conclusions are explored in the following papers (9, 22).


1986 ◽  
Vol 55 (5) ◽  
pp. 866-881 ◽  
Author(s):  
R. E. Flamm ◽  
R. M. Harris-Warrick

In the preceding paper, we describe how dopamine, octopamine, and serotonin modulate the neural circuit generating a well-described motor pattern, the pyloric rhythm of the stomatogastric ganglion in the spiny lobster, Panulirus interruptus. In this paper, we identify the neurons within the pyloric circuit that are directly affected by each amine. We accomplished this by isolating each pyloric neuron from all known synaptic input, using a combination of Lucifer yellow photoinactivation of presynaptic neurons and pharmacological blockade by pyloric neurotransmitters. Dopamine, octopamine, and serotonin were bath applied to the preparation, and the responses of synaptically isolated neurons were recorded. Each amine had a unique constellation of effects on the neurons of the pyloric circuit. Almost every neuron in the circuit was directly affected by each amine. Dopamine and octopamine modulated every neuron, whereas serotonin affected four of the six cell types. Each amine had multiple effects among pyloric neurons including the induction of endogenous rhythmic bursting activity, initiation or enhancement of tonic firing activity, and inhibition accompanied by hyperpolarization. All three amines induced rhythmic bursting in one neuron (the AB neuron), but the form of the underlying slow-wave membrane-potential oscillations was different with octopamine than with dopamine and serotonin. Our knowledge of the effects of each amine on each pyloric neuron, combined with the extensive knowledge of the synaptic organization of the pyloric circuit, has allowed us to explain qualitatively the major aspects of the unique variants of the pyloric motor rhythm that each amine produces in the synaptically intact circuit.


1997 ◽  
Vol 77 (2) ◽  
pp. 599-610 ◽  
Author(s):  
Patsy S. Dickinson ◽  
Wesley P. Fairfield ◽  
John R. Hetling ◽  
Jane Hauptman

Dickinson, Patsy S., Wesley P. Fairfield, John R. Hetling, and Jane Hauptman. Neurotransmitter interactions in the stomatogastric system of the spiny lobster: one peptide alters the response of a central pattern generator to a second peptide. J. Neurophysiol. 77: 599–610, 1997. Two of the peptides found in the stomatogastric nervous system of the spiny lobster, Panulirus interruptus, interacted to modulate the activity of the cardiac sac motor pattern. In the isolated stomatogastric ganglion, red-pigment-concentrating hormone (RPCH), but not proctolin, activated the bursting activity in the inferior ventricular (IV) neurons that drives the cardiac sac pattern. The cardiac sac pattern normally ceased within 15 min after the end of RPCH superfusion. However, when proctolin was applied within a few minutes of that time, it was likewise able to induce cardiac sac activity. Similarly, proctolin applied together with subthreshold RPCH induced cardiac sac bursting. The amplitude of the excitatory postsynaptic potentials from the IV neurons to the cardiac sac dilator neuron CD2 (1 of the 2 major motor neurons in the cardiac sac system) was potentiated in the presence of both proctolin and RPCH. The potentiation in RPCH was much greater than in proctolin alone. However, the potentiation inproctolin after RPCH was equivalent to that recorded in RPCH alone. Although we do not yet understand the mechanisms for these interactions of the two modulators, this study provides an example of one factor that can determine the “state” of the system that is critical in determining the effect of a modulator that is “state dependent,” and it provides evidence for yet another level of flexibility in the motor output of this system.


2003 ◽  
Vol 89 (4) ◽  
pp. 1902-1909 ◽  
Author(s):  
Y. Zhang ◽  
J. N. MacLean ◽  
W. F. An ◽  
C. C. Lanning ◽  
R. M. Harris-Warrick

The transient potassium current ( I A) plays an important role in shaping the firing properties of pyloric neurons in the stomatogastric ganglion (STG) of the spiny lobster, Panulirus interruptus. The shal gene encodes I A in pyloric neurons. However, when we over-expressed the lobster Shal protein by shal RNA injection into the pyloric dilator (PD) neuron, the increased I A had somewhat different properties from the endogenous I A. The recently cloned K-channel interacting proteins (KChIPs) can modify vertebrate Kv4 channels in cloned cell lines. When we co-expressed hKChIP1 with lobster shal in Xenopusoocytes or lobster PD neurons, they produced A-currents resembling the endogenous I A in PD neurons; compared with currents evoked by shal alone, their voltage for half inactivation was depolarized, their kinetics of inactivation were slowed, and their recovery from inactivation was accelerated. We also co-expressed shal in PD neurons with lobster frequenin, which encodes a protein belonging to the same EF-hand family of Ca2+ sensing proteins as hKChIP. Frequenin also restored most of properties of the shal-evoked currents to those of the endogenous A-currents, but the time course of recovery from inactivation was not corrected. These results suggest that lobster shal proteins normally interact with proteins in the KChIP/frequenin family to produce the transient potassium current in pyloric neurons.


Author(s):  
K. Shankar Narayan ◽  
Kailash C. Gupta ◽  
Tohru Okigaki

The biological effects of short-wave ultraviolet light has generally been described in terms of changes in cell growth or survival rates and production of chromosomal aberrations. Ultrastructural changes following exposure of cells to ultraviolet light, particularly at 265 nm, have not been reported.We have developed a means of irradiating populations of cells grown in vitro to a monochromatic ultraviolet laser beam at a wavelength of 265 nm based on the method of Johnson. The cell types studies were: i) WI-38, a human diploid fibroblast; ii) CMP, a human adenocarcinoma cell line; and iii) Don C-II, a Chinese hamster fibroblast cell strain. The cells were exposed either in situ or in suspension to the ultraviolet laser (UVL) beam. Irradiated cell populations were studied either "immediately" or following growth for 1-8 days after irradiation.Differential sensitivity, as measured by survival rates were observed in the three cell types studied. Pattern of ultrastructural changes were also different in the three cell types.


2021 ◽  
Vol 22 (15) ◽  
pp. 8042
Author(s):  
Mengmeng Jin ◽  
Katja Akgün ◽  
Tjalf Ziemssen ◽  
Markus Kipp ◽  
Rene Günther ◽  
...  

Amyotrophic lateral sclerosis (ALS) is a progressive disease leading to the degeneration of motor neurons (MNs). Neuroinflammation is involved in the pathogenesis of ALS; however, interactions of specific immune cell types and MNs are not well studied. We recently found a shift toward T helper (Th)1/Th17 cell-mediated, pro-inflammatory immune responses in the peripheral immune system of ALS patients, which positively correlated with disease severity and progression. Whether Th17 cells or their central mediator, Interleukin-17 (IL-17), directly affects human motor neuron survival is currently unknown. Here, we evaluated the contribution of Th17 cells and IL-17 on MN degeneration using the co-culture of iPSC-derived MNs of fused in sarcoma (FUS)-ALS patients and isogenic controls with Th17 lymphocytes derived from ALS patients, healthy controls, and multiple sclerosis (MS) patients (positive control). Only Th17 cells from MS patients induced severe MN degeneration in FUS-ALS as well as in wildtype MNs. Their main effector, IL-17A, yielded in a dose-dependent decline of the viability and neurite length of MNs. Surprisingly, IL-17F did not influence MNs. Importantly, neutralizing IL-17A and anti-IL-17 receptor A treatment reverted all effects of IL-17A. Our results offer compelling evidence that Th17 cells and IL-17A do directly contribute to MN degeneration.


2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Dvir Gur ◽  
Emily J. Bain ◽  
Kory R. Johnson ◽  
Andy J. Aman ◽  
H. Amalia Pasoili ◽  
...  

AbstractSkin color patterns are ubiquitous in nature, impact social behavior, predator avoidance, and protection from ultraviolet irradiation. A leading model system for vertebrate skin patterning is the zebrafish; its alternating blue stripes and yellow interstripes depend on light-reflecting cells called iridophores. It was suggested that the zebrafish’s color pattern arises from a single type of iridophore migrating differentially to stripes and interstripes. However, here we find that iridophores do not migrate between stripes and interstripes but instead differentiate and proliferate in-place, based on their micro-environment. RNA-sequencing analysis further reveals that stripe and interstripe iridophores have different transcriptomic states, while cryogenic-scanning-electron-microscopy and micro-X-ray diffraction identify different crystal-arrays architectures, indicating that stripe and interstripe iridophores are different cell types. Based on these results, we present an alternative model of skin patterning in zebrafish in which distinct iridophore crystallotypes containing specialized, physiologically responsive, organelles arise in stripe and interstripe by in-situ differentiation.


2021 ◽  
Vol 22 (9) ◽  
pp. 4960
Author(s):  
Natalia Guillén Díaz-Maroto ◽  
Gemma Garcia-Vicién ◽  
Giovanna Polcaro ◽  
María Bañuls ◽  
Nerea Albert ◽  
...  

Heterotypic interactions between newly transformed cells and normal surrounding cells define tumor’s fate in incipient carcinomas. Once homeostasis has been lost, normal resident fibroblasts become carcinoma-associated fibroblasts, conferring protumorogenic properties on these normal cells. Here we describe the IL1β-mediated interplay between cancer cells and normal colonic myofibroblasts (NCFs), which bestows differential sensitivity to cytotoxic drugs on tumor cells. We used NCFs, their conditioned media (CM), and cocultures with tumor cells to characterize the IL1β-mediated crosstalk between both cell types. We silenced IL1β in tumor cells to demonstrate that such cells do not exert an influence on NCFs inflammatory phenotype. Our results shows that IL1β is overexpressed in cocultured tumor cells. IL1β enables paracrine signaling in myofibroblasts, converting them into inflammatory-CAFs (iCAF). IL1β-stimulated-NCF-CM induces migration and differential sensitivity to oxaliplatin in colorectal tumor cells. Such chemoprotective effect has not been evidenced for TGFβ1-driven NCFs. IL1β induces the loss of a myofibroblastic phenotype in NCFs and acquisition of iCAF traits. In conclusion, IL1β-secreted by cancer cells modify surrounding normal fibroblasts to confer protumorogenic features on them, particularly tolerance to cytotoxic drugs. The use of IL1β-blocking agents might help to avoid the iCAF traits acquisition and consequently to counteract the protumorogenic actions these cells.


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