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Laser ablation of Dbx1 neurons in the pre-Bötzinger complex stops inspiratory rhythm and impairs output in neonatal mice.

Wang X, Hayes JA, Revill AL, Song H, Kottick A, Vann NC, LaMar MD, Picardo MC, Akins VT, Funk GD, Del Negro CA - Elife (2014)

Bottom Line: To understand the neural origins of rhythmic behavior one must characterize the central pattern generator circuit and quantify the population size needed to sustain functionality.Breathing-related interneurons of the brainstem pre-Bötzinger complex (preBötC) that putatively comprise the core respiratory rhythm generator in mammals are derived from Dbx1-expressing precursors.These results demonstrate that a single canonical interneuron class generates respiratory rhythm and contributes in a premotor capacity, whereas these functions are normally attributed to discrete populations.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States.

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Cumulative tally of laser ablations for preBötC-surface slices (magenta) and control slices whose surface exposes the ventral respiratory column, not preBötC (cyan).The total tally and the individual side tallies are shown for each preparation. Black bars show the mean. For preBötC-surface slices, the tally was always lower on the side that was being lesioned when the rhythm stopped because rhythm cessation halted the ablation sequence.DOI:http://dx.doi.org/10.7554/eLife.03427.009
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fig2s2: Cumulative tally of laser ablations for preBötC-surface slices (magenta) and control slices whose surface exposes the ventral respiratory column, not preBötC (cyan).The total tally and the individual side tallies are shown for each preparation. Black bars show the mean. For preBötC-surface slices, the tally was always lower on the side that was being lesioned when the rhythm stopped because rhythm cessation halted the ablation sequence.DOI:http://dx.doi.org/10.7554/eLife.03427.009

Mentions: The frequency and amplitude of inspiratory motor output diminished at the onset of the ablation phase (Figures 2A and 3A). XII amplitude decreased steeply with the tally of ablated cells, and then stabilized at 44% of its pre-lesion value (SD 4%, SEM 1%, suction electrode recordings are reported in normalized arbitrary units). Frequency, however, continued to decrease (i.e., cycle period increased) throughout the ablation phase. Initially, within the first dozen ablations, the average decrease in respiratory frequency was nearly twofold, and it continued to fall steeply until rhythm cessation (range of frequencies: 0.22–0.007 Hz, Figure 3B [inset shows bi-exponential increase in cycle period], n = 5 slices). Furthermore, the rhythm destabilized during the ablation phase. We defined regularity score (RS) as the ratio of the present cycle period with respect to the mean period over 10 prior cycles (see ‘Materials and methods’ for RS formula). Cycle-to-cycle variations in RS indicate irregularity; the system is trending slower when RS exceeds unity. The RS of preBötC-surface slices measured 1–9 during the ablation phase (Figure 3C). Respiratory rhythm ceased altogether after an average of 85 confirmed Dbx1 neuron ablations in preBötC-surface slices (SD 44, SEM 20, range 42–137, n = 5 slices), well before exhausting the average list of 705 targets per slice. These ablations were bilateral and the tally reflects the sum of both sides (Figure 2—figure supplement 2). The representative experiment in Figure 2A shows rhythm cessation after 62 confirmed ablations, corresponding to 9% of the total 677 detected targets.10.7554/eLife.03427.007Figure 2.Cumulative serial ablation of Dbx1 neurons in preBötC-surface slices (A) and control slices whose surface exposes the ventral respiratory column, not preBötC (B).


Laser ablation of Dbx1 neurons in the pre-Bötzinger complex stops inspiratory rhythm and impairs output in neonatal mice.

Wang X, Hayes JA, Revill AL, Song H, Kottick A, Vann NC, LaMar MD, Picardo MC, Akins VT, Funk GD, Del Negro CA - Elife (2014)

Cumulative tally of laser ablations for preBötC-surface slices (magenta) and control slices whose surface exposes the ventral respiratory column, not preBötC (cyan).The total tally and the individual side tallies are shown for each preparation. Black bars show the mean. For preBötC-surface slices, the tally was always lower on the side that was being lesioned when the rhythm stopped because rhythm cessation halted the ablation sequence.DOI:http://dx.doi.org/10.7554/eLife.03427.009
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129438&req=5

fig2s2: Cumulative tally of laser ablations for preBötC-surface slices (magenta) and control slices whose surface exposes the ventral respiratory column, not preBötC (cyan).The total tally and the individual side tallies are shown for each preparation. Black bars show the mean. For preBötC-surface slices, the tally was always lower on the side that was being lesioned when the rhythm stopped because rhythm cessation halted the ablation sequence.DOI:http://dx.doi.org/10.7554/eLife.03427.009
Mentions: The frequency and amplitude of inspiratory motor output diminished at the onset of the ablation phase (Figures 2A and 3A). XII amplitude decreased steeply with the tally of ablated cells, and then stabilized at 44% of its pre-lesion value (SD 4%, SEM 1%, suction electrode recordings are reported in normalized arbitrary units). Frequency, however, continued to decrease (i.e., cycle period increased) throughout the ablation phase. Initially, within the first dozen ablations, the average decrease in respiratory frequency was nearly twofold, and it continued to fall steeply until rhythm cessation (range of frequencies: 0.22–0.007 Hz, Figure 3B [inset shows bi-exponential increase in cycle period], n = 5 slices). Furthermore, the rhythm destabilized during the ablation phase. We defined regularity score (RS) as the ratio of the present cycle period with respect to the mean period over 10 prior cycles (see ‘Materials and methods’ for RS formula). Cycle-to-cycle variations in RS indicate irregularity; the system is trending slower when RS exceeds unity. The RS of preBötC-surface slices measured 1–9 during the ablation phase (Figure 3C). Respiratory rhythm ceased altogether after an average of 85 confirmed Dbx1 neuron ablations in preBötC-surface slices (SD 44, SEM 20, range 42–137, n = 5 slices), well before exhausting the average list of 705 targets per slice. These ablations were bilateral and the tally reflects the sum of both sides (Figure 2—figure supplement 2). The representative experiment in Figure 2A shows rhythm cessation after 62 confirmed ablations, corresponding to 9% of the total 677 detected targets.10.7554/eLife.03427.007Figure 2.Cumulative serial ablation of Dbx1 neurons in preBötC-surface slices (A) and control slices whose surface exposes the ventral respiratory column, not preBötC (B).

Bottom Line: To understand the neural origins of rhythmic behavior one must characterize the central pattern generator circuit and quantify the population size needed to sustain functionality.Breathing-related interneurons of the brainstem pre-Bötzinger complex (preBötC) that putatively comprise the core respiratory rhythm generator in mammals are derived from Dbx1-expressing precursors.These results demonstrate that a single canonical interneuron class generates respiratory rhythm and contributes in a premotor capacity, whereas these functions are normally attributed to discrete populations.

View Article: PubMed Central - PubMed

Affiliation: Department of Applied Science, The College of William and Mary, Williamsburg, United States.

Show MeSH
Related in: MedlinePlus