Evidence for a Novel Bursting Mechanism in Rodent Trigeminal Neurons

Negro, Christopher A. Del; Hsiao, Chie-Fang; Chandler, Scott H.; Garfinkel, Alan

doi:10.1016/s0006-3495(98)77504-6

Cited by 89 publications

(54 citation statements)

References 29 publications

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“…In ∼70% of bursts (from 27 NCX KO SANs), there was also a gradual slowing (by 56 ± 3%) of the Ca transient frequency within the burst (Fig. 4 A and B), a phenomenon reminiscent of spike adaptation in neurons (23,24).…”

Section: Resultsmentioning

confidence: 94%

“…4). This slowing is reminiscent of spike adaptation (23,24), a phenomenon well-described in neuronal and chromaffin cells and thought to be caused by activation of Ca-dependent K currents (22,23,36). Big K (41) and TRPM4 channels (40) are present in the SAN, and SAN dysfunction occurs after ablation of Small K channels (42).…”

Section: Parallel Mechanisms Between Ncx Ko Pacemaker Activity and Burstmentioning

confidence: 99%

See 1 more Smart Citation

Burst pacemaker activity of the sinoatrial node in sodium–calcium exchanger knockout mice

Torrente¹,

Zhang²,

Zaini³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

109

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In sinoatrial node (SAN) cells, electrogenic sodium-calcium exchange (NCX) is the dominant calcium (Ca) efflux mechanism. However, the role of NCX in the generation of SAN automaticity is controversial. To investigate the contribution of NCX to pacemaking in the SAN, we performed optical voltage mapping and high-speed 2D laser scanning confocal microscopy (LSCM) of Ca dynamics in an ex vivo intact SAN/atrial tissue preparation from atrial-specific NCX knockout (KO) mice. These mice lack P waves on electrocardiograms, and isolated NCX KO SAN cells are quiescent. Voltage mapping revealed disorganized and arrhythmic depolarizations within the NCX KO SAN that failed to propagate into the atria. LSCM revealed intermittent bursts of Ca transients. Bursts were accompanied by rising diastolic Ca, culminating in long pauses dominated by Ca waves. The L-type Ca channel agonist BayK8644 reduced the rate of Ca transients and inhibited burst generation in the NCX KO SAN whereas the Ca buffer 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid (acetoxymethyl ester) (BAPTA AM) did the opposite. These results suggest that cellular Ca accumulation hinders spontaneous depolarization in the NCX KO SAN, possibly by inhibiting L-type Ca currents. The funny current (I f ) blocker ivabradine also suppressed NCX KO SAN automaticity. We conclude that pacemaker activity is present in the NCX KO SAN, generated by a mechanism that depends upon I f . However, the absence of NCX-mediated depolarization in combination with impaired Ca efflux results in intermittent bursts of pacemaker activity, reminiscent of human sinus node dysfunction and "tachy-brady" syndrome.sinoatrial node | sodium-calcium exchange | pacemaker activity | arrhythmia | intracellular calcium P hysiological heart rhythm originates in the sinoatrial node (SAN), a cluster of specialized pacemaker cells located on the endocardial surface of the right atrium (RA). SAN dysfunction (SND) leads to serious arrhythmias characterized by pathological pauses, often alternating with rapid heart rates or atrial fibrillation (1). Each year in the United States, close to 200,000 patients affected with SAN disease require surgical implantation of an electronic pacemaker (2). Therefore, advances in our understanding of SAN pacemaker activity are essential for developing new therapies to avoid this costly procedure and its related morbidity.In SAN pacemaker cells, action potentials (APs) are thought to be triggered by spontaneous diastolic depolarization (SDD) produced by a coupled system of cellular "clocks" (3). The first clock, known as the "membrane clock," initiates SDD in response to inward funny current (I f ) carried mostly by HCN4 channels (4) although other ion channels, like voltage-dependent Ca channels, have also been implicated (5). The second (and more controversial) clock is referred to as the "Ca clock." This clock produces a depolarizing current in late diastole when local Ca released by ryanodine receptors (RyRs) on the sarcoplasmic reticulum (SR) is extruded by the e...

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Section: Resultsmentioning

confidence: 94%

Section: Parallel Mechanisms Between Ncx Ko Pacemaker Activity and Burstmentioning

confidence: 99%

Burst pacemaker activity of the sinoatrial node in sodium–calcium exchanger knockout mice

Torrente¹,

Zhang²,

Zaini³

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

109

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“…Such a bursting occurs in rodent trigeminal interneurons [Del Negro et al 1998], and it is exhibited by the FitzHugh-Rinzel model [Rinzel, 1987, see Figs. 80 and 81), Rush-Rinzel model [1994], Chay-Cook model [Bertram et al, 1995], Wu-Baer [1998] model, andPernarowski [1994] polynomial model [de Vries, 1998].…”

Section: "Subhopf/hopf " Burstingmentioning

confidence: 99%

Neural Excitability, Spiking and Bursting

Izhikevich

2000

Int. J. Bifurcation Chaos

1,842

1,581

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Bifurcation mechanisms involved in the generation of action potentials (spikes) by neurons are reviewed here. We show how the type of bifurcation determines the neuro-computational properties of the cells. For example, when the rest state is near a saddle-node bifurcation, the cell can fire all-or-none spikes with an arbitrary low frequency, it has a well-defined threshold manifold, and it acts as an integrator ; i.e. the higher the frequency of incoming pulses, the sooner it fires. In contrast, when the rest state is near an Andronov-Hopf bifurcation, the cell fires in a certain frequency range, its spikes are not all-or-none, it does not have a well-defined threshold manifold, it can fire in response to an inhibitory pulse, and it acts as a resonator ; i.e. it responds preferentially to a certain (resonant) frequency of the input. Increasing the input frequency may actually delay or terminate its firing.We also describe the phenomenon of neural bursting, and we use geometric bifurcation theory to extend the existing classification of bursters, including many new types. We discuss how the type of burster defines its neuro-computational properties, and we show that different bursters can interact, synchronize and process information differently.

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“…Thanks to a repeated sequence of spikes in the bursting, there are many hypotheses on the importance of bursting activities in the neural information transmission [3,[7][8][9][10]; for example, (a) bursts are necessary to overcome the synaptic transmission failure, (b) bursts are more reliable than single spikes in evoking responses in postsynaptic neurons, and (c) bursts can be used for selective communication between neurons. There are several representative examples of bursting neurons such as intrinsically bursting neurons and chattering neurons in the cortex [11,12], thalamic relay neurons and thalamic reticular neurons in the thalamus [13][14][15], hippocampal pyramidal neurons [16], Purkinje cells in the cerebellum [17], pancreatic β-cells [18][19][20], and respiratory neurons in pre-Botzinger complex [21,22]. These bursting neurons exhibit two different patterns of synchronization due to the slow and the fast timescales of bursting activity.…”

Section: Introductionmentioning

confidence: 99%

Effect of network architecture on burst and spike synchronization in a scale-free network of bursting neurons

Kim

Lim

2016

Neural Networks

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We investigate the effect of network architecture on burst and spike synchronization in a directed scale-free network (SFN) of bursting neurons, evolved via two independent α− and β−processes.The α−process corresponds to a directed version of the Barabási-Albert SFN model with growth and preferential attachment, while for the β−process only preferential attachments between preexisting nodes are made without addition of new nodes. We first consider the "pure" α−process of symmetric preferential attachment (with the same in-and out-degrees), and study emergence of burst and spike synchronization by varying the coupling strength J and the noise intensity D for a fixed attachment degree. Characterizations of burst and spike synchronization are also made by employing realistic order parameters and statistical-mechanical measures. Next, we choose appropriate values of J and D where only the burst synchronization occurs, and investigate the effect of the scale-free connectivity on the burst synchronization by varying (1) the symmetric attachment degree and (2) the asymmetry parameter (representing deviation from the symmetric case) in the α−process, and (3) the occurrence probability of the β−process. In all these three cases, changes in the type and the degree of population synchronization are studied in connection with the network topology such as the degree distribution, the average path length L p , and the betweenness centralization B c . It is thus found that not only L p and B c (affecting global communication between nodes) but also the in-degree distribution (affecting individual dynamics) are important network factors for effective population synchronization in SFNs.

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Evidence for a Novel Bursting Mechanism in Rodent Trigeminal Neurons

Cited by 89 publications

References 29 publications

Burst pacemaker activity of the sinoatrial node in sodium–calcium exchanger knockout mice

Burst pacemaker activity of the sinoatrial node in sodium–calcium exchanger knockout mice

Neural Excitability, Spiking and Bursting

Effect of network architecture on burst and spike synchronization in a scale-free network of bursting neurons

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