Effects of haloperidol and phentolamine on the crustacean cardiac ganglion

Haloperidol (a dopamine D₂ blocker in vertebrates) and phentolamine (an α-adrenergic blocker) alter the pattern of bursting by the isolated cardiac ganglion of the lobster when perfused at concentrations of 10^?6–10^?5 mol/l. Both drugs decrease the frequency of bursting and increase burst duration. They are most effective in slowing the ganglion when applied selectively to the anterior ganglionic trunk, the same region of the ganglion where dopamine (DA) and 5-hydroxytryptamine (5HT) are most effective in speeding up bursting. When exogenous monoamine transmitters are applied in the presence of 3×10^?6 mol/l haloperidol, the effect of 5HT, but not of DA, is significantly reduced. At the same concentration, phentolamine does not suppress the actions of DA, 5HT or noradrenaline (NA). Both haloperidol and phentolamine significantly alter the properties of endogenous burst-organizing potentials (driver potentials) generated by motorneurons in the ganglion. It is possible that the effects of these drugs on bursting reflect alteration of endogenous electrical properties of the constituent neurons, rather than receptor antagonism.     

Dopamine and 5-hydroxytryptamine actions on the cardiac ganglion of the lobster Homarus americanus

The cardioexcitor monoamines dopamine (DA) and 5-hydroxytryptamine (5HT) accelerate bursting by isolated cardiac ganglia of the lobster Homarusamericanus most effectively when they act on a region of the ganglionic trunk anterior to the small cells which have been considered the pacemakers of the system. 5HT may exert its acceleratory action by depolarizing cell processes. Neither the somata nor the spike-initiating zones of the small cells have to be directly exposed to 5HT or DA in order for acceleration to occur. When 5HT is applied selectively to the small cells bursts are prolonged, probably as a result of increases in the duration of the endogenous burst-organizing potentials (driver potentials) generated by these neurons. This action on the small cells can lead to prolonged and intensified bursts of the full ganglion during the onset of 5HT action when the whole ganglion is exposed to the monoamine. Neither DA nor 5HT has a direct effect on the characteristics of large cell (motorneuron) driver potentials. Accepted: 3 September 1997     

Endogenous burst capability in a neuron of the gastric mill pattern generator of the spiny lobster Panulirus interruptus

The gastric system of the lobster stomatogastric ganglion has previously been thought to include no neurons capable of endogenous bursting. We describe conditions under which one of the motorneurons, the CP cell, can burst endogenously in a free-running manner in the absence of other phasic network activity. Isolated preparations of the foregut nervous system were used, and the CP bursting was either spontaneous or was activated by continuous stimulation of an input nerve. Three criteria were applied to establish the endogenous nature of such burst generation in CP: absence of phasic input, reset of the bursting pattern by pulses of current in a characteristic phase-dependent manner, and modulation of burst rate by sustained injected current. (1) The firing of other cells which are known to be related synaptically to CP was monitored in nerve records. These other cells were either silent or fired only tonically. Cross-correlograms showed that CP bursting was not ascribable to phasic activity in these other network cells. (2) A depolarizing current pulse of sufficient strength injected intracellularly between bursts triggered a burst prematurely and reset the subsequent rhythm. A hyperpolarizing pulse during a burst terminated it and reset the subsequent rhythm. Reset behavior was similar to that described for other endogenous bursters. (3) Application of a positive-going ramp current initially caused an increase in burst rate, as described for other endogenous bursters. However, further depolarization caused a slower burst rate due to lengthening of the individual bursts, although mean firing frequency continued to increase throughout the range tested. Such free-running endogenous repetitive bursting appeared to result from the CP's ability to produce slow regenerative depolarizations (“plateau potentials”). When bursting was present, so was the plateau property, as determined by I–V analysis and by the ability of brief current pulses to trigger and terminate bursts. The previous inability to observe endogenous bursting in preparations with central input removed may be due to the usual absence of the plateau property in such preparations.     

Characterization of buccal motor programs elicited by a cholinergic agonist applied to the cerebral ganglion of Aplysia californica

Applying the non-hydrolyzable cholinergic agonist carbachol (CCh) to the cerebral ganglion of Aplysia elicits sustained, regular bursts of activity in the buccal ganglia resembling those seen during biting. The threshold for bursting is 10^2–4 M. Bursting begins after a 2 to 5 min delay. The burst frequency increases over the first 5 bursts, reaching a plateau value of 3 per minute. Bursting is maintained for over 10 min. Some of the effects of CCh may be attributed to its ability to depolarize and fire CBI-2, a command-like neuron in the cerebral ganglion that initiates biting. CBI-2 is also depolarized by ACh, and by stimulating peripheral sensory nerves. Excitation of CBI-2 caused by carbachol is partially blocked by the muscarinic antagonist atropine. We examined whether CCh-induced bursting is modified in ganglia taken from Aplysia that previously experienced treatments inhibiting feeding, such as satiation, head shock contingent or non-contingent with food, and training animals with an inedible food. No treatment consistently and repeatedly affected the latency, the peak burst period, the length of time that bursting was maintained, or the threshold CCh concentration for eliciting bursting. However, there was a decrease in the rate of the buildup of the buccal ganglion program in previously satiated animals.     

Neurohormonal alteration of integrative properties of the cardiac ganglion of the lobster Homarus americanus.

The spontaneous burst discharges of isolated lobster (Homarus americanus) cardiac ganglia were recorded with a spaced array of electrodes. Small regions (less than 1 mm) of the ganglion were exposed to the cardioexcitor neurohormone in extracts of pericardial organs (XPO) or to 10(-5) M 5-hydroxytryptamine (5HT). All axons were excited (increased mean firing frequency, f) by both substances, but only by applications in the region between the soma (but excluding it) and proximal site of impulse initiation. Units not so exposed changed their f relatively little despite f increases of as much as threefold in exposed units and changes in burst rate and overall length. Regularity and grouping of all impulse activity into bursts was never disturbed. 5HT increases burst rate at any point of application. The increases are larger if small cells are affected than if only large cells are exposed. Burst length decreases except when the pacemaker is affected. In contrast, XPO affects neither burst rate or length unless small cells are affected. Length is increased if non-pacemaker small cells are affected; both rate and length increase if the pacemaker is affected. The pacemaker usually exhibits an f of intermediate value. Rate changes are not simply related to its f. A small cell can "burst" in the absence of impulses from any other cells. XPO may enhance endogenous "driver potentials," while 5HT may excite by depolarizing at limited sites.     

Neural control of olfaction and tentacle movements by serotonin and dopamine in terrestrial snail

We investigated the role of serotonin (5HT) and dopamine (DA) in the regulation of olfactory system function and odor-evoked tentacle movements in the snail Helix. Preparations of the posterior tentacle (including sensory pad, tentacular ganglion and olfactory nerve) or central ganglia with attached posterior tentacles were exposed to cineole odorant and the evoked responses were affected by prior application of 5HT or DA or their precursors 5-hydroxytryptophan (5HTP) and l-DOPA, respectively. 5HT applications decreased cineole-evoked responses recorded in the olfactory nerve and hyperpolarized the identified tentacle retractor muscle motoneuron MtC3, while DA applications led to the opposite changes. 5HTP and l-DOPA modified MtC3 activity comparable to 5HT and DA action. DA was also found to decrease the amplitude of spontaneous local field potential oscillations in the procerebrum, a central olfactory structure. In vivo studies demonstrated that injection of 5HTP in freely moving snails reduced the tentacle withdrawal response to aversive ethyl acetate odorant, whereas the injection of l-DOPA increased responses to “neutral” cineole and aversive ethyl acetate odorants. Our data suggest that 5HT and DA affect the peripheral (sensory epithelium and tentacular ganglion), the central (procerebrum), and the single motor neuron (withdrawal motoneuron MtC3) level of the snail’s nervous system.     

Cholinergic activation of the lobster cardiac ganglion

The frequency of rhythmic burst activity of the isolated lobster cardiac ganglion is increased by exogenously applied acetylcholine and muscarinic agonists. Responses of individual motor neurons isolated from the ganglion by transection consist of a slow depolarization and repetitive bursting. The pharmacological profile of the receptors mediating this response is similar to that of vertebrate neuronal muscarinic receptors. Isolated ganglia incubated in the presence of [3H]-choline (18-19 h) exhibited radiolabelled acetylcholine accumulation. It is suggested that ganglionic excitation may be accomplished by extrinsic or intrinsic activation of muscarinic receptors on the motor neurons.     

Branchial musculature of a venerid clam: pharmacology,distribution, and innervation

This study was meant to analyze the neural control of the branchial muscles of the clam Mercenaria mercenaria. Gills isolated from the animal contract in response to 5-hydroxytryptamine (5HT), dopamine (DA), and acetylcholine (ACh); but the ACh contraction occurred only if the gills had been pretreated with the cholinesterase inhibitor eserine. The 5HT antagonists cyproheptadine and mianserin blocked the contractile effects of all of the agonists. However, gills exposed to the 5HT antagonists and eserine relaxed in response to ACh. The DA antagonist SCH-83566 inhibited the effects of DA, but had no effect on contractions induced by 5HT and ACh. The ACh antagonist hexamethonium inhibited both the excitatory and inhibitory effects of ACh, but had no effect on contractions induced by 5HT and DA. 5HT and DA in gill tissue were visualized by using immunohistochemistry. Within each gill filament are dorsoventral neurons running adjacent to the epithelium and containing immunoreactive 5HT and DA. A complex network of 5HT-positive fibers is associated with the septa, blood vessels, and muscles, whereas DA-positive fibers are restricted to the septa. We propose that 5HT is the excitatory transmitter to the gill muscles, and that DA and ACh exert their excitatory effects by stimulating 5HT motor nerves. ACh may also be an inhibitory transmitter of the muscles.     

The Sites of Action of Pericardial Organ Extract and 5-Hydroxytryptamine in the Decapod Crustacean Heart

Responses of isolated, perfused hearts of Homarm americanusto brief, internal application of extracts of pericardial organs(PO's) ofCancer borealis, or 5-hydroxytryptamine (5HT) are verysimilar over a thousand-told range of concentration: an increasein rate and amplitude of beating. These reach their maxima afterwashing out has begun, and recover within ten minutes. Externalapplication is ineffective and the substances do not interactwith effects of stretch stimulation. Intracellular recordingfrom heart muscle fibers reveals facilitation of depolarizationto bursts at heart beat frequencies. There may be some effectof 5HT directly on neuromuscular facilitation. Responses recordedfrom isolated cardiac ganglia show increased burst rate, burstduration, or both. Thresholds and the range of concentrationsfor which coordinated responses are recorded correspond to thosefor perfused hearts. It is concluded that the major sites ofaction of PO extract and 5HT are in the cardiac ganglion. 5HTtachyphlaxis and LSD block effects of 5HT, but not of PO extractor accelerator nerve stimulation. Intracellular recordings fromthe large ganglion cells show no effects on resting, synaptic,or spike potentials. Changes in membrane potential to currentpulses revealed no changes in membrane resistance or in theresistance of the electrotonic pathway between cells. Resultsof selective application to large or small cells suggested thatPO extract may contain a rate-increasing substance and one prolongingthe duration of bursts. The former, and 5HT, may influence pacemakerpotentials; the latter may increase the number of spikes a unitcan produce before becoming refractory.     

Dopamine and nicotine, but not serotonin, modulate the crustacean ventilatory pattern generator.

Dopamine (DA) causes a dose-dependent increase in the frequency of motor neuron bursts [virtual ventilation (fR)] produced by deafferented crab ventilatory pattern generators (CPGv). Domperidone, a D2-specific DA antagonist, by itself reversibly depresses fR and also blocks the stimulatory effects of DA. Serotonin (5HT) has no direct effects on this CPGv. Nicotine also causes dramatic dose-dependent increases in the frequency of motor bursts from the CPGv. The action is triphasic, beginning with an initial reversal of burst pattern typical of reversed-mode ventilation, followed by a 2- to 3-min period of depression and then a long period of elevated burst rate. Acetylcholine chloride (ACh) alone is ineffective, but in the presence of eserine is moderately stimulatory. The inhibitory effects of nicotine are only partially blocked by curare. The excitatory action of nicotine is blocked by prior perfusion of domperidone, but not by SKF-83566.HCl, a D1-specific DA antagonist. SKF-83566 had no effects on the ongoing pattern of firing. These observations support the hypothesis that dopaminergic pathways are involved in the maintenance of the CPGv rhythm and that the acceleratory effects of nicotine may involve release of DA either directly or via stimulation of atypical ACh receptors at intraganglionic sites.     

Simulation of bursting activity in theHelix RPa1 neuron: Role of calcium ions

A model of bursting activity in the RPal neuron of the snailHelix pomatia has been developed. In this model, calcium conductances do not play a key role in generation of slow oscillations of membrane potential (MP). The possibility of simulating the maintenance of bursting in the presence of cadmium ions is shown. Inclusion in the model of the calcium-inactivated calcium conductance makes it possible to reproduce both adaptation of the neuron to constant polarizing current, which modifies bursting, and the development of slow inward current when MP is clamped at different phases at the slow wave. In our simulations, the characteristic properties of bursts (such as an increase in the frequency of action potentials and a decrease in spike undershoot at the beginning of a burst) are due to the cumulative inactivation of potassium current. The advantages of the presented mathematical model of bursting compared with other models are discussed.Neirofiziologiya/Neurophysiology, Vol. 26, No. 5, pp. 373–381, September–October, 1994.     

基于最大锋电位间隔的爆发检测自适应算法

在各种类型的培养神经元网络、哺乳动物中枢神经系统和切片中,都可以观察到爆发。爆发是空间-时间放电模式的重要特征,它由一系列高频率发放的连续动作电位组成,由于在时间尺度上的复杂性,使其辨识和探测存在许多困难。自适应算法利用爆发外部锋电位间隔超过爆发内部锋电位间隔的累加和识别爆发本身。基于该算法原理,以爆发内部最大锋电位间隔参数作为确定爆发的约束条件,改进爆发检测自适应算法。实验结果表明,改进算法可以有效地避免爆发的漏检和错检,较准确地检测出神经元的爆发活动,确定爆发活动的数目和持续时间等,爆发检测的平均准确率为93.8%,比原自适应算法提高了35.3%。     

Dopamine and nicotine,but not serotonin,modulate the crustacean ventilatory pattern generator

Dopamine (DA) causes a dose-dependent increase in the frequency of motor neuron bursts [virtual ventilation (f_R)] produced by deafferented crab ventilatory pattern generators (CPG_v). Domperidone, a D₂-specific DA antagonist, by itself reversibly depresses f_R and also blocks the stimulatory effects of DA. Serotonin (5HT) has no direct effects on this CPG_v. Nicotine also causes dramatic dose-dependent increases in the frequency of motor bursts from the CPG_v. The action is triphasic, beginning with an initial reversal of burst pattern typical of reversed-mode ventilation, followed by a 2- to 3-min period of depression and then a long period of elevated burst rate. Acetylcholine chloride (ACh) alone is ineffective, but in the presence of eserine is moderately stimulatory. The inhibitory effects of nicotine are only partially blocked by curare. The excitatory action of nicotine is blocked by prior perfusion of domperidone, but not by SKF-83566.HCl, a D₁-specific DA antagonist. SKF-83566 had no effects on the ongoing pattern of firing. These observations support the hypothesis that dopaminergic pathways are involved in the maintenance of the CPG_v rhythm and that the acceleratory effects of nicotine may involve release of DA either directly or via stimulation of atypical ACh receptors at intraganglionic sites. © 1992 John Wiley & Sons, Inc.     

OLFACTORY INPUTS TO A BURSTING SEROTONERGIC INTERNEURON IN A TERRESTRIAL MOLLUSC

Olfactory fiber tracts in Limax maximus Linnaeus terminate inthe cerebral ganglion, and arborize near the metacerebral giantcell (MGC). In the preparation herein described the serotonergicMGC fires in bursts. Electrical stimulation of an olfactorynerve (OfN) elicits complex postsynaptic potentials (PSPs) inthe ipsilateral MGC that disrupt its bursting. Rigidly controlledstimulation of a nose with natural or synthetic odors elicitsa brief burst of compound action potentials in the ipsilateralOfN (en passant recording). Olfactory stimulation of a noseleads to PSPs in the ipsilateral MGC which can cause an increasein its firing rate and alter the firing pattern of the contralateralMGC. Olfactory stimulation failed to activate the feeding neuralnetwork of which the MGC is part. MGC bursting is discussed. ¹Present address: 2326 Woodglen St., Richardson, Texas, 75081,U.S.A. Send reprint requests to A. Gelperin. (Received 31 January 1980;     

Ionic mechanisms underlying spontaneous CA1 neuronal firing in Ca2+-free solution

Hippocampal CA1 neurons exposed to zero-[Ca(2+)] solutions can generate periodic spontaneous synchronized activity in the absence of synaptic function. Experiments using hippocampal slices showed that, after exposure to zero-[Ca(2+)](0) solution, CA1 pyramidal cells depolarized 5-10 mV and started firing spontaneous action potentials. Spontaneous single neuron activity appeared in singlets or was grouped into bursts of two or three action potentials. A 16-compartment, 23-variable cable model of a CA1 pyramidal neuron was developed to study mechanisms of spontaneous neuronal bursting in a calcium-free extracellular solution. In the model, five active currents (a fast sodium current, a persistent sodium current, an A-type transient potassium current, a delayed rectifier potassium current, and a muscarinic potassium current) are included in the somatic compartment. The model simulates the spontaneous bursting behavior of neurons in calcium-free solutions. The mechanisms underlying several aspects of bursting are studied, including the generation of triplet bursts, spike duration, burst termination, after-depolarization behavior, and the prolonged inactive period between bursts. We show that the small persistent sodium current can play a key role in spontaneous CA1 activity in zero-calcium solutions. In particular, it is necessary for the generation of an after-depolarizing potential and prolongs both individual bursts and the interburst interval.     

Cellular properties and modulation of the stomatogastric ganglion neurons of a stomatopod,Squilla oratoria

Cellular properties and modulation of the identified neurons of the posterior cardiac plate-pyloric system in the stomatogastric ganglion of a stomatopod, Squilla oratoria, were studied electrophysiologically. Each class of neurons involved in the cyclic bursting activity was able to trigger an endogenous, slow depolarizing potential (termed a driver potential) which sustained bursting. Endogenous oscillatory properties were demonstrated by the phase reset behavior in response to brief stimuli during ongoing rhythm. The driver potential was produced by membrane voltage-dependent activation and terminated by an active repolarization. Striking enhancement of bursting properties of all the cell types was induced by synaptic activation via extrinsic nerves, seen as increases in amplitude or duration of driver potentials, spiking rate during a burst, and bursting rate. The motor pattern produced under the influence of extrinsic modulatory inputs continued for a long time, relative to that in the absence of activation of modulatory inputs. Voltage-dependent conductance mechanisms underlying postinhibitory rebound and driver potential responses were modified by inputs. It is concluded that endogenous cellular properties, as well as synaptic circuitry and extrinsic inputs, contribute to generation of the rhythmic motor pattern, and that a motor system and its component neurons have been highly conserved during evolution between stomatopods and decapods.Abbreviations AB anterior burster neuron - CoG commissural ganglion - CPG central pattern generator - lvn lateral ventricular nerve - OG oesophageal ganglion - pcp posterior cardiac plate - PCP pcp constrictor neuron - PD pyloric dilator neuron - PY pyloric constrictor neuron - son superior oesophageal nerve - STG stomatogastric ganglion - stn stomatogastric nerve     

Dual effects of proctolin on the rhythmic burst activity of the cardiac ganglion

The neuropeptide proctolin has distinguishable excitatory effects upon premotor cells and motorneurons of Homarus cardiac ganglion. Proctolin's excitation of the small, premotor, posterior cells is rapid in onset (5–10 s) and readily reversible (< 3 min). Prolonged bursts in small cells often produce a “doublet” ganglionic burst mode via interactions with large motorneuron burst-generating driver potentials. In contrast to small cell response, proctolin's direct excitatory effects upon motorneuron are slow in onset (60–90 s to peak) and long-lasting (10–20 min). The latter include: (a) a concentration-dependent (10^?9–10^?7M) depolarization of the somatic membrane potential; (b) increases in burst frequency and (c) enhancement of the rate of depolarization of the interburst pacemaker potential. Experiments on isolated large cells indicate: (a) the slow depolarization is produced by a decrease in the resting G_K and (b) proctolin can produce or enhance motorneuron autorhythmicity. A two-tiered non-hierarchical network model is proposed. The differential pharmacodynamics exhibited by the two cell types accounts for the sequential modes of ganglionic burst activity produced by proctolin.     

Functional Organization of the Cardiac Ganglion of the Lobster, Homarus americanus

External recording and stimulation, techniques were used to determine which neurons and interactions are essential for production of the periodic burst discharge in the lobster cardiac ganglion. Burst activity can be modulated by brief single shocks applied to the four small cells, but not by similar stimulation of the five large cells, suggesting that normally one or more small cells primarily determine burst rate and duration. Repetitive electrical stimulation of large cells initiates spike activity in small cells, probably via excitatory synaptic and/or electrotonic connections which may normally act to prolong bursts and decrease burst rate. Transection of the ganglion can result in burst activity in small cells in the partial or complete absence of large cell spike activity, but large cells isolated from small cell excitatory synaptic input by transection or by application of dinitrophenol do not burst. Generally, transections which decrease excitatory feedback to small cells are accompanied by an increase in burst rate, but mean spike frequency over an entire burst cycle stabilizes at the original level within 10–30 min for various groups of cells whose spike-initiating sites are still intact. These and previous results suggest that the system is two layered: one or more small cells generate the burst pattern and impose it on the large cells which are the system's motorneurons.     

Kynuretic acid blocks spontaneous epileptiform bursts induced by 4-aminopyridine in rat amygdala neurons

The effects of excitatory amino acid receptor antagonists, kynuretic acid and DL-2-amino-5-phosphonovalerate (DL-APV), on spontaneous epileptiform activity induced by 4-aminopyridine (4-AP) were studied in rat amygdala slices using intracellular recording techniques. Five to ten minutes after switching to 4-AP containing solution, spontaneous epileptiform bursts were observed in 37 out of 48 slices studied. The spontaneous epileptiform events consisted of an initial burst followed by a number of afterdischarges. Superfusion with kynuretic acid, a nonspecific excitatory amino acid receptor antagonist, reversibly reduced the duration of the spontaneous bursting discharges in a dose-dependent manner. The frequency of spontaneous bursting was also decreased. The IC50, estimated from the graph of the concentration-response relationship, was approximately 130 microM. In contrast to kynuretic acid, DL-APV, which is a specific N-methyl-D-aspartate (NMDA) receptor antagonist, failed to block the spontaneous bursting. These results suggest that activation of excitatory amino acid receptors of non-NMDA type is involved in the generation of propagation of spontaneous epileptiform events induced by 4-AP in the neurons of basolateral amygdala.     

Self-Organization on Social Media: Endo-Exo Bursts and Baseline Fluctuations

A salient dynamic property of social media is bursting behavior. In this paper, we study bursting behavior in terms of the temporal relation between a preceding baseline fluctuation and the successive burst response using a frequency time series of 3,000 keywords on Twitter. We found that there is a fluctuation threshold up to which the burst size increases as the fluctuation increases and that above the threshold, there appears a variety of burst sizes. We call this threshold the critical threshold. Investigating this threshold in relation to endogenous bursts and exogenous bursts based on peak ratio and burst size reveals that the bursts below this threshold are endogenously caused and above this threshold, exogenous bursts emerge. Analysis of the 3,000 keywords shows that all the nouns have both endogenous and exogenous origins of bursts and that each keyword has a critical threshold in the baseline fluctuation value to distinguish between the two. Having a threshold for an input value for activating the system implies that Twitter is an excitable medium. These findings are useful for characterizing how excitable a keyword is on Twitter and could be used, for example, to predict the response to particular information on social media.