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Mechanisms Leading to Rhythm Cessation in the Respiratory PreBötzinger Complex Due to Piecewise Cumulative Neuronal Deletions(1,2,3).

Song H, Hayes JA, Vann NC, Drew LaMar M, Del Negro CA - eNeuro (2015)

Bottom Line: When the recruitment rate drops below 1 neuron/ms the network stops spontaneous rhythmic activity.Neurons that play pre-eminent roles in rhythmogenesis include those that commence spiking during the quiescent phase between respiratory bursts and those with a high number of incoming synapses, which both play key roles in recruitment, i.e., recurrent excitation leading to network bursts.This study provides a theoretical framework for the operating mechanism of mammalian central pattern generator networks and their susceptibility to loss-of-function in the case of disease or neurodegeneration.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Applied Science, The College of William & Mary , Williamsburg, Virginia 23187-8795.

ABSTRACT
The mammalian breathing rhythm putatively originates from Dbx1-derived interneurons in the preBötzinger complex (preBötC) of the ventral medulla. Cumulative deletion of ∼15% of Dbx1 preBötC neurons in an in vitro breathing model stops rhythmic bursts of respiratory-related motor output. Here we assemble in silico models of preBötC networks using random graphs for structure, and ordinary differential equations for dynamics, to examine the mechanisms responsible for the loss of spontaneous respiratory rhythm and motor output measured experimentally in vitro. Model networks subjected to cellular ablations similarly discontinue functionality. However, our analyses indicate that model preBötC networks remain topologically intact even after rhythm cessation, suggesting that dynamics coupled with structural properties of the underlying network are responsible for rhythm cessation. Simulations show that cumulative cellular ablations diminish the number of neurons that can be recruited to spike per unit time. When the recruitment rate drops below 1 neuron/ms the network stops spontaneous rhythmic activity. Neurons that play pre-eminent roles in rhythmogenesis include those that commence spiking during the quiescent phase between respiratory bursts and those with a high number of incoming synapses, which both play key roles in recruitment, i.e., recurrent excitation leading to network bursts. Selectively ablating neurons with many incoming synapses impairs recurrent excitation and stops spontaneous rhythmic activity and motor output with lower ablation tallies compared with random deletions. This study provides a theoretical framework for the operating mechanism of mammalian central pattern generator networks and their susceptibility to loss-of-function in the case of disease or neurodegeneration.

No MeSH data available.


Model network bursts do not diminish during ablations sequences. Running time spike histogram (top, red) for one experiment. Time calibration (1 min) is displayed. a, The fifth network-wide burst. b, A network-wide burst after 21 deletions. c, The last network-wide burst after 31 deletions. The running time spike histogram (vertical calibration 10 spikes/ms) and average membrane potential (VM, vertical calibration 20 mV) for all remaining neurons in the network for network-wide bursts (a, b, and c) are shown at higher sweep speed. Cells 190, 42, and 271 from the model system are shown individually. Baseline membrane potential (–60 mV) and time calibration (1 s) apply to all traces.
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Figure 3: Model network bursts do not diminish during ablations sequences. Running time spike histogram (top, red) for one experiment. Time calibration (1 min) is displayed. a, The fifth network-wide burst. b, A network-wide burst after 21 deletions. c, The last network-wide burst after 31 deletions. The running time spike histogram (vertical calibration 10 spikes/ms) and average membrane potential (VM, vertical calibration 20 mV) for all remaining neurons in the network for network-wide bursts (a, b, and c) are shown at higher sweep speed. Cells 190, 42, and 271 from the model system are shown individually. Baseline membrane potential (–60 mV) and time calibration (1 s) apply to all traces.

Mentions: Next we addressed how cumulative ablations affect network excitability, which encompasses a range of cellular and synaptic factors. Network burst output, which was quantified by the running time spike histogram (Fig. 3, red traces), did not decline during the ablation sequence. Figure 3 shows three individual bursts, including the final one, with faster sweep speed to emphasize their similarity. Likewise, there was no systematic drop in baseline membrane potential, as quantified by the average voltage trace for all constituent neurons in the remaining network, and shown for three representative cells (Fig. 3, black traces).


Mechanisms Leading to Rhythm Cessation in the Respiratory PreBötzinger Complex Due to Piecewise Cumulative Neuronal Deletions(1,2,3).

Song H, Hayes JA, Vann NC, Drew LaMar M, Del Negro CA - eNeuro (2015)

Model network bursts do not diminish during ablations sequences. Running time spike histogram (top, red) for one experiment. Time calibration (1 min) is displayed. a, The fifth network-wide burst. b, A network-wide burst after 21 deletions. c, The last network-wide burst after 31 deletions. The running time spike histogram (vertical calibration 10 spikes/ms) and average membrane potential (VM, vertical calibration 20 mV) for all remaining neurons in the network for network-wide bursts (a, b, and c) are shown at higher sweep speed. Cells 190, 42, and 271 from the model system are shown individually. Baseline membrane potential (–60 mV) and time calibration (1 s) apply to all traces.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4596029&req=5

Figure 3: Model network bursts do not diminish during ablations sequences. Running time spike histogram (top, red) for one experiment. Time calibration (1 min) is displayed. a, The fifth network-wide burst. b, A network-wide burst after 21 deletions. c, The last network-wide burst after 31 deletions. The running time spike histogram (vertical calibration 10 spikes/ms) and average membrane potential (VM, vertical calibration 20 mV) for all remaining neurons in the network for network-wide bursts (a, b, and c) are shown at higher sweep speed. Cells 190, 42, and 271 from the model system are shown individually. Baseline membrane potential (–60 mV) and time calibration (1 s) apply to all traces.
Mentions: Next we addressed how cumulative ablations affect network excitability, which encompasses a range of cellular and synaptic factors. Network burst output, which was quantified by the running time spike histogram (Fig. 3, red traces), did not decline during the ablation sequence. Figure 3 shows three individual bursts, including the final one, with faster sweep speed to emphasize their similarity. Likewise, there was no systematic drop in baseline membrane potential, as quantified by the average voltage trace for all constituent neurons in the remaining network, and shown for three representative cells (Fig. 3, black traces).

Bottom Line: When the recruitment rate drops below 1 neuron/ms the network stops spontaneous rhythmic activity.Neurons that play pre-eminent roles in rhythmogenesis include those that commence spiking during the quiescent phase between respiratory bursts and those with a high number of incoming synapses, which both play key roles in recruitment, i.e., recurrent excitation leading to network bursts.This study provides a theoretical framework for the operating mechanism of mammalian central pattern generator networks and their susceptibility to loss-of-function in the case of disease or neurodegeneration.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Applied Science, The College of William & Mary , Williamsburg, Virginia 23187-8795.

ABSTRACT
The mammalian breathing rhythm putatively originates from Dbx1-derived interneurons in the preBötzinger complex (preBötC) of the ventral medulla. Cumulative deletion of ∼15% of Dbx1 preBötC neurons in an in vitro breathing model stops rhythmic bursts of respiratory-related motor output. Here we assemble in silico models of preBötC networks using random graphs for structure, and ordinary differential equations for dynamics, to examine the mechanisms responsible for the loss of spontaneous respiratory rhythm and motor output measured experimentally in vitro. Model networks subjected to cellular ablations similarly discontinue functionality. However, our analyses indicate that model preBötC networks remain topologically intact even after rhythm cessation, suggesting that dynamics coupled with structural properties of the underlying network are responsible for rhythm cessation. Simulations show that cumulative cellular ablations diminish the number of neurons that can be recruited to spike per unit time. When the recruitment rate drops below 1 neuron/ms the network stops spontaneous rhythmic activity. Neurons that play pre-eminent roles in rhythmogenesis include those that commence spiking during the quiescent phase between respiratory bursts and those with a high number of incoming synapses, which both play key roles in recruitment, i.e., recurrent excitation leading to network bursts. Selectively ablating neurons with many incoming synapses impairs recurrent excitation and stops spontaneous rhythmic activity and motor output with lower ablation tallies compared with random deletions. This study provides a theoretical framework for the operating mechanism of mammalian central pattern generator networks and their susceptibility to loss-of-function in the case of disease or neurodegeneration.

No MeSH data available.