Conditional Bursters Research Articles

First return maps for the dynamics of synaptically coupled conditional bursters

The pre-Bötzinger complex (preBötc) in the mammalian brainstem has an important role in generating respiratory rhythms. An influential differential equation model for the activity of individual neurons in the preBötc yields transitions from quiescence to bursting to tonic spiking as a parameter is varied. Further, past work has established that bursting dynamics can arise from a pair of tonic model cells coupled with synaptic excitation. In this paper, we analytically derive one- and two-dimensional maps from the differential equations for a self-coupled neuron and a two-neuron network, respectively. Using a combination of analysis and simulations of these maps, we explore the possible forms of dynamics that the model networks can produce as well as which transitions between dynamic regimes are mathematically possible.

Persistent Synchronized Bursting Activity in Cortical Tissues With Low Magnesium Concentration: A Modeling Study

We explore the mechanism of synchronized bursting activity with frequency of approximately 10 Hz that appears in cortical tissues at low extracellular magnesium concentration [Mg2+]o. We hypothesize that this activity is persistent, namely coexists with the quiescent state and depends on slow N-methyl-D-aspartate (NMDA) conductances. To explore this hypothesis, we construct and investigate a conductance-based model of excitatory cortical networks. Population bursting activity can persist for physiological values of the NMDA decay time constant (approximately 100 ms). Neurons are synchronized at the time scale of bursts but not of single spikes. A reduced model of a cell coupled to itself can encompass most of this highly synchronized network behavior and is analyzed using the fast-slow method. Synchronized bursts appear for intermediate values of the NMDA conductance g(NMDA) if NMDA conductances are not too fast. Regular spiking activity appears for larger g(NMDA). If the single cell is a conditional burster, persistent synchronized bursts become more robust. Weakly synchronized states appear for zero AMPA conductance g(AMPA). Enhancing g(AMPA) increases both synchrony and the number of spikes within bursts and decreases the bursting frequency. Too strong g(AMPA), however, prevents the activity because it enhances neuronal intrinsic adaptation. When [Mg2+]o is increased, higher g(NMDA) values are needed to maintain bursting activity. Bursting frequency decreases with [Mg2+]o, and the network is silent with physiological [Mg2+]o. Inhibition weakly decreases the bursting frequency if inhibitory cells receive enough NMDA-mediated excitation. This study explains the importance of conditional bursters in layer V in supporting epileptiform activity at low [Mg2+]o.

Noradrenergic responses of neurones in the mediolateral part of the lateral septum: α 1-adrenergic depolarization and rhythmic bursting activities, and α 2-adrenergic hyperpolarization from guinea pig brain slices

Bath application of noradrenaline on neurones of class A, B and C within the mediolateral part of the lateral septum from guinea pig brain slices elicited depolarization (through α 1-adrenoceptors) or hyperpolarization (through α 2-adrenoceptors) and rhythmic bursting activities (through α 1-adrenoceptors). A co-existence of these two types of adrenoceptors (α 1 and α 2) mediating opposite effects on membrane excitability was sometimes observed on the same neurone. Three types (I, II and III) of neurones were identified on the basis of their bursting properties during noradrenaline application. With the bursting activities persisting under tetrodotoxin and their frequency being sensitive to changes in membrane potential, these neurones could be considered as conditional bursters. An afterdepolarizing potential could promote burst initiation in the three types of neurones. Neuronal input resistance decreased at the afterdepolarizing potential peak. Application of low-Na + medium blocked the generation of bursts and afterdepolarizing potentials induced by noradrenaline in the three types of neurones. Furthermore, the bursts were dependent on the presence of Ca 2+ in the medium in a subpopulation of neurones. We conclude that afterdepolarizing potentials and bursts induced by noradrenaline are generated by a cationic conductance largely permeable to Na + in neurones of the mediolateral part of the lateral septum.

Neurons in the guinea-pig lateral septum generate rhythmic bursting activities, in vitro, following application of carbachol

We used intracellular recordings in a guinea pig brain slice preparation to characterize the actions of carbachol in neurons of the mediolateral part of the lateral septum (LSml). Bath application of carbachol elicited depolarization and rhythmic bursting activities in a majority of neurons (61.5%) through muscarinic receptors. Within the LSml, three types (I, II and III) of rhythmic bursting neurons could be distinguished on the basis of the properties (waveform, duration and amplitude) of their bursts induced by carbachol. In the three types of neurons, the frequency of the bursts depended on the membrane potential whereas the addition of tetrodotoxin to the bath did not suppress carbachol-induced rhythmic bursting activities. Therefore, these events were not driven by synaptic mechanisms but originated from endogenous properties of LSml neurons activated by carbachol. Thus, LSml neurons can be considered as conditional bursters.

Mechanisms of gastric rhythm generation in the isolated stomatogastric ganglion of spiny lobsters: bursting pacemaker potentials, synaptic interactions, and muscarinic modulation.

1. The gastric central pattern generator (CPG), located in the stomatogastric ganglion (STG) of the spiny lobster (Panulirus interruptus), is nonrhythmic when deprived of neuromodulatory inputs from anterior ganglia. Leaving these inputs intact in vitro can sustain a gastric rhythm but also introduces numerous, uncontrolled and largely unknown modulatory and synaptic influences that greatly complicate analysis of this CPG. 2. Here we induced gastric rhythms in the isolated STG, by superfusing a specific modulator, the muscarinic agonist, pilocarpine. Muscarinic agents sustain vigorous gastric rhythms in the isolated STG. Our aim was to analyze the pattern-generating functions of the restricted gastric circuit, free of complicating influences from other ganglia, and under specific (muscarinic) modulation. 3. We used combinations of multiple cell hyperpolarizations, photodeletions, and synaptic blockade by picrotoxin to assess the pattern-generating role of individual gastric neurons and to study the activity of subcircuits. 4. Four identified gastric neurons [lateral gastric (LG), dorsal gastric (DG), 2 electrically coupled lateral posterior gastric (2LPGs)] acted as pattern-generating cells. They showed bursting pacemaker potentials (BPPs), i.e., plateau (or driver) potentials that underlay bursts of axonal spikes and slow, interburst depolarizing potentials that underlay repetitive burst activity. LG and DG, at least, became conditional bursters, able to burst repetitively because of intrinsic oscillations. The other gastric neurons behaved mainly as follower cells and derived their rhythmic bursting from synaptic coupling to the pattern-generator cells and from their own intrinsic (but nonoscillatory) properties. 5. The pattern-generating neurons form a novel "kernel" circuit that works by the cooperative interaction of cellular properties and synaptic connectivity. 6. This study constitutes the first complete and fully consistent analysis of pattern generation in the gastric network of the isolated STG. These mechanisms pertain to muscarinic rhythms in particular but also, we suggest, to gastric rhythm generation and CPG function in general. We suggest that 1) rhythmicity normally depends on the induction of bursty membrane properties in at least some component neurons; 2) different subcircuits can produce rhythmic patterns and may be activated by different modulators; and 3) the gastric network shares several important "building blocks" with CPGs that have been analyzed in other systems. 7. Muscarinic inputs are implicated as an important gastric regulator. We compare these responses with the reported modulatory actions of the anterior pyloric modulator (AMP), an identified, putatively cholinergic input interneuron that may act via muscarinic mechanisms.

Elevated temperature alters the ionic dependence of amine-induced pacemaker activity in a conditional burster neuron.

The anterior burster neuron of the lobster (Panulirus interruptus) stomatogastric ganglion is a conditional burster that functions as the primary pacemaker for the pyloric motor network. When modulatory inputs to this cell are blocked, it loses its bursting properties and becomes quiescent. Applications of the monoamines, dopamine, octopamine or serotonin restore rhythmic bursting in this cell (Flamm and Harris-Warrick 1986). At 15 degrees C, serotonin- and octopamine-induced oscillations depend critically upon sodium entry (blocked by low sodium saline or tetrodotoxin); dopamine-induced oscillations depend upon calcium entry (blocked by reduced extracellular calcium; Harris-Warrick and Flamm 1987). We show here that the ionic dependence of amine-induced oscillations in the anterior burster cell differs at 15 and 21 degrees C. At 21 degrees C, all amines have the potential to induce rhythmic oscillations in saline containing tetrodotoxin. At the elevated temperature and in tetrodotoxin, both calcium and sodium currents are essential for the maintenance of dopamine-induced oscillations; serotonin-induced oscillations do not depend upon either calcium or sodium alone; octopamine-induced oscillations do not depend upon calcium and show a variable dependence upon sodium. Thus, multiple ionic mechanisms, which vary with both the modulator and the ambient temperature, can be recruited to support rhythmic activity in a conditional burster neuron.

Multiple mechanisms of bursting in a conditional bursting neuron

The anterior burster (AB) neuron in the stomatogastric ganglion of the spiny lobster, Panulirus interruptus, is a conditional burster in the pyloric motor circuit. Bath application of the monoamines dopamine, serotonin, and octopamine induces rhythmic bursting pacemaker potentials in a silent, synaptically isolated AB cell. However, each amine produces a unique and characteristic burst shape, resulting from different ionic dependences of the burst mechanisms. Bursting induced by serotonin or octopamine is critically dependent upon sodium entry through tetrodotoxin-sensitive channels; dopamine-induced bursting is not TTX-sensitive. Dopamine-induced bursting is abolished when extracellular calcium is reduced to 25% of normal; serotonin- and octopamine-induced bursts continue in this saline, although they are abolished in salines with calcium reduced to 10% or less of normal. Quantitative differences between the amines are also seen in the tetraethylammonium (TEA) sensitivity of the burst amplitude and in the dependence of the interburst hyperpolarization on extracellular potassium. These experiments demonstrate that there are both quantitative and qualitative differences in the ionic currents underlying every phase of the bursts induced by the 3 amines. Thus, a single neuron can burst via more than one ionic mechanism.

Potassium channel blockade induces rhythmic activity in a conditional burster neuron

In the lobster stomatogastric ganglion the Anterior Burster (AB) neuron loses its rhythmic bursting capabilities when isolated from all synaptic input. Here we report that compounds which reduce the current through several different types of potassium channels induce bursting in isolated AB neurons. These results suggest that when quiescent, this neuron has all the conductances necessary to support bursting, but bursting is actively inhibited by tonic potassium conductances.

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

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.