Glutamatergic N2v Cells Are Central Pattern Generator Interneurons of the Lymnaea Feeding System: New Model for Rhythm Generation

1997 ◽  
Vol 78 (6) ◽  
pp. 3396-3407 ◽  
Author(s):  
M. J. Brierley ◽  
M. S. Yeoman ◽  
P. R. Benjamin
Keyword(s):  
Central Pattern Generator ◽  
Synaptic Connection ◽  
Giant Cells ◽  
Pattern Generator ◽  
Synaptic Connections ◽  
Rhythm Generation ◽  
Feeding System ◽  
New Model ◽  
Feeding Cycle ◽  
Protraction Phase

Brierley, M. J., M. S. Yeoman, and P. R. Benjamin. Glutamatergic N2v cells are central pattern generator interneurons of the Lymnaea feeding system: new model for rhythm generation. J. Neurophysiol. 78: 3396–3407, 1997. We aimed to show that the paired N2v (N2 ventral) plateauing cells of the buccal ganglia are important central pattern generator (CPG) interneurons of the Lymnaea feeding system. N2v plateauing is phase-locked to the rest of the CPG network in a slow oscillator (SO)-driven fictive feeding rhythm. The phase of the rhythm is reset by artificially evoked N2v bursts, a characteristic of CPG neurons. N2v cells have extensive input and output synaptic connections with the rest of the CPG network and the modulatory SO cell and cerebral giant cells (CGCs). Synaptic input from the protraction phase interneurons N1M (excitatory), N1L (inhibitory), and SO (inhibitory-excitatory) are likely to contribute to a ramp-shaped prepotential that triggers the N2v plateau. The prepotential has a highly complex waveform due to progressive changes in the amplitude of the component synaptic potentials. Most significant is the facilitation of the excitatory component of the SO → N2v monosynaptic connection. None of the other CPG interneurons has the appropriate input synaptic connections to terminate the N2v plateaus. The modulatory function of acetylcholine (ACh), the transmitter of the SO and N1M/N1Ls, was examined. Focal application of ACh (50-ms pulses) onto the N2v cells reproduced the SO → N2v biphasic synaptic response but also induced long-term plateauing (20–60 s). N2d cells show no endogenous ability to plateau, but this can be induced by focal applications of ACh. The N2v cells inhibit the N3 tonic (N3t) but not the N3 phasic (N3p) CPG interneurons. The N2v → N3t inhibitory synaptic connection is important in timing N3t activity. The N3t cells recover from this inhibition and fire during the swallow phase of the feeding pattern. Feedback N2v inhibition to the SO, N1L protraction phase interneurons prevents them firing during the retraction phase of the feeding cycle. The N2v → N1M synaptic connection was weak and only found in 50% of preparations. A weak N2v → CGC inhibitory connection prevents the CGCs firing during the rasp (N2) phase of the feeding cycle. These data allowed a new model for the Lymnaea feeding CPG to be proposed. This emphasizes that each of the six types of CPG interneuron has a unique set of synaptic connections, all of which contribute to the generation of a full CPG pattern.

Central pattern generator interneurons are targets for the modulatory serotonergic cerebral giant cells in the feeding system of Lymnaea

1996 ◽  
Vol 75 (1) ◽  
pp. 11-25 ◽  
Author(s):  
M. S. Yeoman ◽  
M. J. Brierley ◽  
P. R. Benjamin
Keyword(s):  
Firing Rate ◽  
Central Pattern Generator ◽  
Frequency Control ◽  
Giant Cells ◽  
Pattern Generator ◽  
Feeding System ◽  
Feeding Rhythm ◽  
Feeding Cycle ◽  
Excitatory Component ◽  
Cell Firing

1. The objective of the experiments was to explore the modulatory functions of the serotonergic cerebral giant cells (CGCs) of the Lymnaea feeding system by examining their synaptic connections with the central pattern generator (CPG) interneurons and the modulatory slow oscillator (SO) interneuron. 2. One type of modulatory function, "gating," requires that the CGCs fire tonically at a minimum of 7 spikes/min. Above this minimum level the CGCs control the frequency of CPG interneuron oscillation-- "frequency control," a second type of modulation. In an SO-driven fictive feeding rhythm, an increase in the frequency of the rhythm, with increased CGC firing rate, resulted from a reduction in the duration of the N1 (protraction) and N2 (rasp) phases of the feeding cycle with little effect on the N3 (swallow) phase. 3. The CGCs excited the N1 phase interneurons SO and N1M (N1 medial) cells but had no consistent effects on the N1 lateral cells. The CGC-->SO postsynaptic response was probably monosynaptic (< or = 200 ms in duration) with unitary 1:1 excitatory postsynaptic potentials (EPSPs) following each CGC spike. The CGC-->N1M excitatory response was slow and nonunitary, and a burst of CGC spikes evoked a depolarization of the N1M cells that lasted up to 10 s and triggered N1M cell bursts. Both CGC-->SO and CGC-->N1M excitatory responses could be mimicked by the focal application of serotonin (5-HT). 4. Both CGC-->SO and CGC-->N1M excitatory connections systematically increased the N1M cell firing rate within the CGCs' physiological firing range (0-40 spikes/min). This was due to both the direct (CGC-->N1M) and indirect (CGC-->SO-->N1M) excitatory synaptic pathways. The CGC-induced increase in N1M cell firing rate probably accounted for the reduced duration of the N1M cell feeding burst by causing a more rapid reversal of the feeding cycle from the N1 phase to the N2 phase. This phase reversal was due to the previously described recurrent inhibitory pathway (N1-->N2 excitation followed by N2-->N1 inhibition). 5. The CGCs' ability to provide a depolarizing drive to the N1M cells meant that this excitatory connection was also likely to be important for gating. 6. Activity in the CGCs produced nonunitary, long-lasting, excitatory postsynaptic responses on the N2 ventral (N2v) CPG interneurons, and these were likely to be involved in both the gating and the frequency control by the CGCs on the N2 phase of the feeding rhythm. Suppressing CGC tonic firing initially increased the duration of the N2v plateau (which determines the duration of the N2 phase of the feeding cycle, frequency function) but eventually led to a loss of N2v plateauing (gating function). 7. Nonunitary, weakly inhibitory CGC-->N2 dorsal responses were recorded that could be mimicked by the application of 5-HT. 8. Spikes in the CGCs evoked 1:1 monosynaptic EPSPs in the N3 tonic (N3t) CPG interneurons. This excitatory effect could be mimicked by the application of 5-HT. Within the physiological range of CGC firing, this excitation did not appear to influence the firing rate of the N3t cells. 9. N3 phasic (N3p) CPG interneurons showed biphasic (hyperpolarizing followed by depolarizing) unitary responses to spikes evoked in the CGCs. The inhibitory synaptic response was maintained in a high-Ca2+/high-Mg2+ (Hi-Di) saline and was mimicked by the focal application of 5-HT, indicating that it was probably monosynaptic. The excitatory component was, however, reduced in a Hi-Di saline, indicating that it was probably polysynaptic. Suppressing the CGCs during an SO-driven feeding rhythm caused the N3p cells to fire less, suggesting that the removal of the excitatory component of the response might be significant. 10. We conclude that the general depolarizing effects of the CGCs on a number of the CP

Simulator for neural networks and action potentials: description and application

1994 ◽  
Vol 71 (1) ◽  
pp. 294-308 ◽  
Author(s):  
I. Ziv ◽  
D. A. Baxter ◽  
J. H. Byrne
Keyword(s):  
Neural Networks ◽  
Central Pattern Generator ◽  
Action Potentials ◽  
Modular Design ◽  
Second Messenger ◽  
Pattern Generator ◽  
Slow Inward Current ◽  
Synaptic Connections ◽  
Different Types ◽  
Voltage Dependent

1. We describe a simulator for neural networks and action potentials (SNNAP) that can simulate up to 30 neurons, each with up to 30 voltage-dependent conductances, 30 electrical synapses, and 30 multicomponent chemical synapses. Voltage-dependent conductances are described by Hodgkin-Huxley type equations, and the contributions of time-dependent synaptic conductances are described by second-order differential equations. The program also incorporates equations for simulating different types of neural modulation and synaptic plasticity. 2. Parameters, initial conditions, and output options for SNNAP are passed to the program through a number of modular ASCII files. These modules can be modified by commonly available text editors that use a conventional (i.e., character based) interface or by an editor incorporated into SNNAP that uses a graphical interface. The modular design facilitates the incorporation of existing modules into new simulations. Thus libraries can be developed of files describing distinctive cell types and files describing distinctive neural networks. 3. Several different types of neurons with distinct biophysical properties and firing properties were simulated by incorporating different combinations of voltage-dependent Na+, Ca2+, and K+ channels as well as Ca(2+)-activated and Ca(2+)-inactivated channels. Simulated cells included those that respond to depolarization with tonic firing, adaptive firing, or plateau potentials as well as endogenous pacemaker and bursting cells. 4. Several types of simple neural networks were simulated that included feed-forward excitatory and inhibitory chemical synaptic connections, a network of electrically coupled cells, and a network with feedback chemical synaptic connections that simulated rhythmic neural activity. In addition, with the use of the equations describing electrical coupling, current flow in a branched neuron with 18 compartments was simulated. 5. Enhancement of excitability and enhancement of transmitter release, produced by modulatory transmitters, were simulated by second-messenger-induced modulation of K+ currents. A depletion model for synaptic depression was also simulated. 6. We also attempted to simulate the features of a more complicated central pattern generator, inspired by the properties of neurons in the buccal ganglia of Aplysia. Dynamic changes in the activity of this central pattern generator were produced by a second-messenger-induced modulation of a slow inward current in one of the neurons.

Feeding CPG in Aplysia Directly Controls Two Distinct Outputs of a Compartmentalized Interneuron That Functions as a CPG Element

2007 ◽  
Vol 98 (6) ◽  
pp. 3796-3801 ◽  
Author(s):  
Kosei Sasaki ◽  
Michael R. Due ◽  
Jian Jing ◽  
Klaudiusz R. Weiss
Keyword(s):  
Action Potentials ◽  
Electrical Coupling ◽  
Motor Program ◽  
Pattern Generator ◽  
Synaptic Connections ◽  
Buccal Ganglion ◽  
Full Size ◽  
Program Generation ◽  
Functional Aspects ◽  
Protraction Phase

In the context of motor program generation in Aplysia, we characterize several functional aspects of intraneuronal compartmentalization in an interganglionic interneuron, CBI-5/6. CBI-5/6 was shown previously to have a cerebral compartment (CC) that includes a soma that does not generate full-size action potentials and a buccal compartment (BC) that does. We find that the synaptic connections made by the BC of CBI-5/6 in the buccal ganglion counter the activity of protraction-phase neurons and reinforce the activity of retraction-phase neurons. In buccal motor programs, the BC of CBI-5/6 fires phasically, and its premature activation can phase advance protraction termination and retraction initiation. Thus the BC of CBI-5/6 can act as an element of the central pattern generator (CPG). During protraction, the CC of CBI-5/6 receives direct excitatory inputs from the CPG elements, B34 and B63, and during retraction, it receives antidromically propagating action potentials that originate in the BC of CBI-5/6. Consequently, in its CC, CBI-5/6 receives depolarizing inputs during both protraction and retraction, and these depolarizations can be transmitted via electrical coupling to other neurons. In contrast, in its BC, CBI-5/6 uses spike-dependent synaptic transmission. Thus the CPG directly and differentially controls the program phases in which the two compartments of CBI-5/6 may transmit information to its targets.

Fast Synaptic Connections From CBIs to Pattern-Generating Neurons in Aplysia: Initiation and Modification of Motor Programs

2003 ◽  
Vol 89 (4) ◽  
pp. 2120-2136 ◽  
Author(s):  
Itay Hurwitz ◽  
Irving Kupfermann ◽  
Klaudiusz R. Weiss
Keyword(s):  
Central Pattern Generator ◽  
Motor Pattern ◽  
Aplysia Californica ◽  
Pattern Generator ◽  
Synaptic Connections ◽  
Motor Patterns ◽  
Motor Programs ◽  
Postsynaptic Potentials ◽  
Buccal Ganglia ◽  
Very High

Consummatory feeding movements in Aplysia californica are organized by a central pattern generator (CPG) in the buccal ganglia. Buccal motor programs similar to those organized by the CPG are also initiated and controlled by the cerebro-buccal interneurons (CBIs), interneurons projecting from the cerebral to the buccal ganglia. To examine the mechanisms by which CBIs affect buccal motor programs, we have explored systematically the synaptic connections from three of the CBIs (CBI-1, CBI-2, CBI-3) to key buccal ganglia CPG neurons (B31/B32, B34, and B63). The CBIs were found to produce monosynaptic excitatory postsynaptic potentials (EPSPs) with both fast and slow components. In this report, we have characterized only the fast component. CBI-2 monosynaptically excites neurons B31/B32, B34, and B63, all of which can initiate motor programs when they are sufficiently stimulated. However, the ability of CBI-2 to initiate a program stems primarily from the excitation of B63. In B31/B32, the size of the EPSPs was relatively small and the threshold for excitation was very high. In addition, preventing firing in either B34 or B63 showed that only a block in B63 firing prevented CBI-2 from initiating programs in response to a brief stimulus. The connections from CBI-2 to the buccal ganglia neurons showed a prominent facilitation. The facilitation contributed to the ability of CBI-2 to initiate a BMP and also led to a change in the form of the BMP. The cholinergic blocker hexamethonium blocked the fast EPSPs induced by CBI-2 in buccal ganglia neurons and also blocked the EPSPs between a number of key CPG neurons within the buccal ganglia. CBI-2 and B63 were able to initiate motor patterns in hexamethonium, although the form of a motor pattern was changed, indicating that non-hexamethonium-sensitive receptors contribute to the ability of these cells to initiate bursts. By contrast to CBI-2, CBI-1 excited B63 but inhibited B34. CBI-3 excited B34 and not B63. The data indicate that CBI-1, -2, and -3 are components of a system that initiates and selects between buccal motor programs. Their behavioral function is likely to depend on which combination of CBIs and CPG elements are activated.

Novel interneuron having hybrid modulatory-central pattern generator properties in the feeding system of the snail, Lymnaea stagnalis

1995 ◽  
Vol 73 (1) ◽  
pp. 112-124 ◽  
Author(s):  
M. S. Yeoman ◽  
A. Vehovszky ◽  
G. Kemenes ◽  
C. J. Elliott ◽  
P. R. Benjamin
Keyword(s):  
Central Pattern Generator ◽  
Lymnaea Stagnalis ◽  
Cell Types ◽  
Pattern Generator ◽  
Feeding System ◽  
Buccal Ganglia ◽  
Steady Current ◽  
Feeding Rhythm ◽  
Symmetrical Pair ◽  
Feeding Rhythms

1. We used intracellular recording techniques to examine the role of a novel type of protraction phase interneuron, the lateral N1 (N1L) in the feeding system of the snail Lymnaea stagnalis. 2. The N1Ls are a bilaterally symmetrical pair of electrotonically coupled interneurons located in the buccal ganglia. Each N1L sends a single axon to the contralateral buccal ganglia. Their neurite processes are confined to the buccal neuropile. 3. In the isolated CNS, depolarization of an N1L is capable of driving a full (N1-->N2-->N3), fast (1 cycle every 5 s) fictive feeding rhythm. This was unlike the previously described N1 medial (N1M) central pattern generator (CPG) interneurons that were only capable of driving a slow, irregular rhythm. Attempts to control the frequency of the fictive feeding rhythm by injecting varying amounts of steady current into the N1Ls were unsuccessful. This contrasts with a modulatory neuron, the slow oscillator (SO), that has very similar firing patterns to the N1Ls, but where the frequency of the rhythm depends on the level of injected current. 4. The N1Ls' ability to drive a fictive feeding rhythm in the isolated preparation was due to their strong, monosynaptic excitatory chemical connection with the N1M CPG interneurons. Bursts of spikes in the N1Ls generated summating excitatory postsynaptic potentials (EPSPs) in the N1Ms to drive them to firing. The SO excited the N1M cells in a similar way, but the EPSPs are strongly facilitatory, unlike the N1L-->N1M connection. 5. Fast (1 cycle every 5 s) fictive feeding rhythms driven by the N1L occurred in the absence of spike activity in the SO modulatory neuron. In contrast, the N1L was usually active in SO-driven rhythms. 6. The ability of the SO to drive the N1L was due to strong electrotonic coupling, SO-->N1L. The weaker coupling in the opposite direction, N1L-->SO, did not allow the N1L to drive the SO. 7. Experiments on semintact lip-brain preparations allowed fictive feeding to be evoked by application of 0.1 M sucrose to the lips (mimicking the normal sensory input) rather than by injection of depolarizing current. Rhythmic bursting, characteristic of fictive feeding, began in both the SO and N1L at exactly the same time, indicating that these two cell types are activated in "parallel" to drive the feeding rhythm. 8. The N1L is also part of the CPG network. It Excited the N2s and inhibited the N3 phasic (N3p) and N3 tonic (N3t) CPG interneurons like the N1Ms.(ABSTRACT TRUNCATED AT 400 WORDS)

Endogenous and Network Properties of LymnaeaFeeding Central Pattern Generator Interneurons

2002 ◽  
Vol 88 (4) ◽  
pp. 1569-1583 ◽  
Author(s):  
Volko A. Straub ◽  
Kevin Staras ◽  
György Kemenes ◽  
Paul R. Benjamin
Keyword(s):  
Central Pattern Generator ◽  
Activity Patterns ◽  
Pattern Generator ◽  
Pattern Generation ◽  
Detailed Knowledge ◽  
Rhythm Generation ◽  
Cell Type ◽  
Intrinsic Properties ◽  
Plateau Potential ◽  
Network Properties

Understanding central pattern generator (CPG) circuits requires a detailed knowledge of the intrinsic cellular properties of the constituent neurons. These properties are poorly understood in most CPGs because of the complexity resulting from interactions with other neurons of the circuit. This is also the case in the feeding network of the snail, Lymnaea, one of the best-characterized CPG networks. We addressed this problem by isolating the interneurons comprising the feeding CPG in cell culture, which enabled us to study their basic intrinsic electrical and pharmacological cellular properties without interference from other network components. These results were then related to the activity patterns of the neurons in the intact feeding network. The most striking finding was the intrinsic generation of plateau potentials by medial N1 (N1M) interneurons. This property is probably critical for rhythm generation in the whole feeding circuit because the N1M interneurons are known to play a pivotal role in the initiation of feeding cycles in response to food. Plateau potential generation in another cell type, the ventral N2 (N2v), appeared to be conditional on the presence of acetylcholine. Examination of the other isolated feeding CPG interneurons [lateral N1 (N1L), dorsal N2 (N2d), phasic N3 (N3p)] and the modulatory slow oscillator (SO) revealed no significant intrinsic properties in relation to pattern generation. Instead, their firing patterns in the circuit appear to be determined largely by cholinergic and glutamatergic synaptic inputs from other CPG interneurons, which were mimicked in culture by application of these transmitters. This is an example of a CPG system where the initiation of each cycle appears to be determined by the intrinsic properties of a key interneuron, N1M, but most other features of the rhythm are probably determined by network interactions.

scholarly journals Phase-Locked Coordination Between Two Rhythmically Active Feeding Structures in the Mollusk Clione limacina. I. Motor Neurons

2002 ◽  
Vol 87 (6) ◽  
pp. 2996-3005 ◽  
Author(s):  
Aleksey Y. Malyshev ◽  
Tigran P. Norekian
Keyword(s):  
Central Pattern Generator ◽  
Motor Neurons ◽  
Electrical Coupling ◽  
Pattern Generator ◽  
Dependent Manner ◽  
Synaptic Connections ◽  
Buccal Ganglia ◽  
Active Feeding ◽  
Clione Limacina ◽  
Specific Phase

Coordination between different motor centers is essential for the orderly production of all complex behaviors, in both vertebrates and invertebrates. The current study revealed that rhythmic activities of two feeding structures of the pteropod mollusk Clione limacina, radula and hooks, which are used to extract the prey from its shell, are highly coordinated in a phase-dependent manner. Hook protraction always coincided with radula retraction, while hook retraction coincided with radula protraction. Thus hooks and radula were always moving in the opposite phases, taking turns grabbing and pulling the prey tissue out of the shell. Identified buccal ganglia motor neurons controlling radula and hooks protraction and retraction were rhythmically active in the same phase-dependent manner. Hook protractor motor neurons were active in the same phase with radula retractor motor neurons, while hook retractor motor neurons burst in phase with radula protractor motor neurons. One of the main mechanisms underlying the phase-locked coordination was electrical coupling between hook protractor and radula retractor motor neurons. In addition, reciprocal inhibitory synaptic connections were found between hook protractor and radula protractor motor neurons. These electrical and inhibitory synaptic connections ensure that rhythmically active hooks and radula controlling motor neurons are coordinated in the specific phase-dependent manner described above. The possible existence of a single multifunctional central pattern generator for both radula and hook motor centers is discussed.

B64, a newly identified central pattern generator element producing a phase switch from protraction to retraction in buccal motor programs of Aplysia californica

1996 ◽  
Vol 75 (4) ◽  
pp. 1327-1344 ◽  
Author(s):  
I. Hurwitz ◽  
A. J. Susswein
Keyword(s):  
Phase Shift ◽  
Central Pattern Generator ◽  
Motor Program ◽  
Pattern Generator ◽  
Synaptic Activity ◽  
Excitatory Postsynaptic Potential ◽  
Motor Programs ◽  
Identified Neuron ◽  
Protraction Phase ◽  
Two Phases

1. Buccal motor programs in Aplysia are characterized by two phases of activity, which represent protraction and retraction of the radula in intact animals. The shift from protraction to retraction is caused by synaptic activity inhibiting neurons that are active during protraction and exciting neurons that are active during retraction. 2. B64, a newly identified neuron present bilaterally in the buccal ganglia, is partially responsible for the phase shift. Stimulating a single B64 causes bilateral inhibition of neurons B31/B32 and other neurons active during protraction and cause bilateral excitation of neurons B4/B5 and other neurons active during retraction. B64 is active throughout retraction. The amplitude and waveforms of the synaptic potentials caused by firing B64 are similar, but not identical, to those seen during retraction. 3. Some of the effects of B64 on B31/B32 and on B4/B5 are monosynaptic, as shown by their maintained presence in high divalent cation seawater, which blocks polysynaptic activity. 4. A brief depolarization of B64 leads to a long-lasting depolarization and firing. The ability of B64 to respond in this way is at least partially caused by an endogenous plateau potential, as this property is still seen after synaptic transmission is blocked. 5. Hyperpolarization of B64 bilaterally and preventing the somata from firing unmasks a large excitatory postsynaptic potential in B64. This procedure does not block the shift from protraction to retraction, indicating that spiking in the B64 somata is not necessary for the phase shift. 6. The firing pattern and synaptic connections of B64 are consistent with the hypothesis that the neuron is part of a central pattern generator underlying buccal motor programs. B64 is monosynaptically inhibited by neurons that are active along with B31/B32, which are responsible for producing the protraction phase of a buccal motor program. During the later portion of the protraction phase B64 is excited. In addition, firing B64 can phase advance and phase delay buccal motor programs. 7. Regulating the firing of B64 can regulate the expression of buccal motor programs. Stimulation of B64 at frequencies of 0.5-1.0 Hz leads to complete inhibition of buccal motor programs, whereas steady-state depolarization of B64 can lead to repetitive bursts of activity.

Central Coordination of Buccal and Pedal Neuronal Activity in the Pond Snail Lymnaea Stagnalis

1988 ◽  
Vol 136 (1) ◽  
pp. 103-123
Author(s):  
M. A. KYRIAKIDES ◽  
C. R. MCCROHAN
Keyword(s):  
Central Pattern Generator ◽  
Body Wall ◽  
Lymnaea Stagnalis ◽  
Pattern Generator ◽  
Pond Snail ◽  
Buccal Ganglion ◽  
Buccal Ganglia ◽  
Feeding Cycle ◽  
Central Coordination

Cyclical synaptic inputs were recorded from identified giant neurones and neuronal cluster cells in the pedal ganglia of Lymnaea stagnalis. They occurred in phase with rhythmical inputs to buccal ganglion motoneurones, which have been shown to originate from interneurones of the buccal central pattern generator for feeding. In pedal neurones, the cyclical inputs were mainly inhibitory, and occurred predominantly during the radula retraction phase of the feeding cycle. Tonic depolarization of higher-order interneurones in the feeding system, to activate the buccal central pattern generator, led to the onset of cyclical inputs to pedal neurones. These inputs were abolished after cutting the cerebrobuccal connectives, supporting the hypothesis that they originate from the buccal ganglia. The possible role of these inputs in coordinating foot and body wall movements with the buccal feeding rhythm is discussed.

scholarly journals Eupnea, tachypnea, and autoresuscitation in a closed-loop respiratory control model

2017 ◽  
Vol 118 (4) ◽  
pp. 2194-2215 ◽  
Author(s):  
Casey O. Diekman ◽  
Peter J. Thomas ◽  
Christopher G. Wilson
Keyword(s):  
Central Pattern Generator ◽  
Closed Loop ◽  
Minute Ventilation ◽  
Respiratory Control ◽  
Pattern Generator ◽  
Control Model ◽  
Open Loop ◽  
Blood Oxygen ◽  
Rhythm Generation ◽  
Metabolic Demand

How sensory information influences the dynamics of rhythm generation varies across systems, and general principles for understanding this aspect of motor control are lacking. Determining the origin of respiratory rhythm generation is challenging because the mechanisms in a central circuit considered in isolation may be different from those in the intact organism. We analyze a closed-loop respiratory control model incorporating a central pattern generator (CPG), the Butera-Rinzel-Smith (BRS) model, together with lung mechanics, oxygen handling, and chemosensory components. We show that 1) embedding the BRS model neuron in a control loop creates a bistable system; 2) although closed-loop and open-loop (isolated) CPG systems both support eupnea-like bursting activity, they do so via distinct mechanisms; 3) chemosensory feedback in the closed loop improves robustness to variable metabolic demand; 4) the BRS model conductances provide an autoresuscitation mechanism for recovery from transient interruption of chemosensory feedback; and 5) the in vitro brain stem CPG slice responds to hypoxia with transient bursting that is qualitatively similar to in silico autoresuscitation. Bistability of bursting and tonic spiking in the closed-loop system corresponds to coexistence of eupnea-like breathing, with normal minute ventilation and blood oxygen level and a tachypnea-like state, with pathologically reduced minute ventilation and critically low blood oxygen. Disruption of the normal breathing rhythm, through either imposition of hypoxia or interruption of chemosensory feedback, can push the system from the eupneic state into the tachypneic state. We use geometric singular perturbation theory to analyze the system dynamics at the boundary separating eupnea-like and tachypnea-like outcomes. NEW & NOTEWORTHY A common challenge facing rhythmic biological processes is the adaptive regulation of central pattern generator (CPG) activity in response to sensory feedback. We apply dynamical systems tools to understand several properties of a closed-loop respiratory control model, including the coexistence of normal and pathological breathing, robustness to changes in metabolic demand, spontaneous autoresuscitation in response to hypoxia, and the distinct mechanisms that underlie rhythmogenesis in the intact control circuit vs. the isolated, open-loop CPG.

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