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Research ArticleConfirmation, Integrative Systems

Resetting the Respiratory Rhythm with a Spinal Central Pattern Generator

Roberto Meza, Nayeli Huidobro, Mayra Moreno-Castillo, Abraham Mendez-Fernandez, Jorge Flores-Hernandez, Amira Flores and Elias Manjarrez
eNeuro 10 April 2019, 6 (2) ENEURO.0116-19.2019; https://doi.org/10.1523/ENEURO.0116-19.2019
Roberto Meza
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México, 72570
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Nayeli Huidobro
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México, 72570
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Mayra Moreno-Castillo
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México, 72570
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Abraham Mendez-Fernandez
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México, 72570
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Jorge Flores-Hernandez
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México, 72570
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Amira Flores
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México, 72570
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Elias Manjarrez
Instituto de Fisiología, Benemérita Universidad Autónoma de Puebla, Puebla, México, 72570
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    Figure 1.

    Scheme of the experimental paradigm. The phrenic nerve activity (PNA) was used to examine the respiratory rhythm. A, A mechanical stimulus (timing indicated with a short rectangle) applied to the pinna elicits a fictive scratching episode (timing indicated with a large rectangle and the TA nerve activity). Such a stimulus was randomly applied after the fourth phrenic nerve discharge. During the scratching episode, there is an increase in the phrenic nerve activity [note the increase in the rectified and integrated PNA activity]. The periodic respiratory rhythm returns after the scratching episode ends. B, A zoom of the timing scheme in A illustrating how the old phase and cophase were measured. The horizontal red arrows illustrate how the old phase and cophase were measured. C, D, The same as A, B but for those mechanical stimuli that did not produce fictive scratching. The triangles illustrate the expected period of the PNA. The vertical black lines represent the experimental PNA. The pink and blue vertical lines indicate the onset and offset of the scratching episode, respectively. The rectangle labeled as “Mech. Stim” illustrates the phase in which the brief mechanical stimulation to the pinna was applied. The rectangle labeled as “Scratching” indicates the duration of the scratching episode.

  • Figure 2.
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    Figure 2.

    Phase analysis performed from recordings of phrenic nerve activity. A, The vertical black marks indicate the phrenic nerve activity before, during, and after the application of mechanical stimuli applied to the pinna able to produce fictive scratching. The magenta and blue marks represent the onset and offset of the scratching episode. The triangles represent the expected period for the respiratory rhythmicity. The horizontal red arrows show the phase shift, which is the difference in phase in the respiratory rhythm as a consequence of the occurrence of the fictive scratching episode. B, The same as A but for those mechanical stimuli not producing fictive scratching. The green marks represent the brief mechanical stimuli. C, Phase-transition graph, constructed by the relationship between the normalized old phase and cophase. Note the tendency of the points toward a horizontal arrangement (i.e., type 0 resetting). Each color is related to each scratching episode that produced a phase shift of the respiratory rhythm. D, Pink circles are the averaged data from C, and the vertical lines are the standard deviation. E, The same as C but for those mechanical stimuli not producing fictive scratching. Each color represents the trials in which the mechanical stimulation to the pinna was unable to change the phase. Note that in this case phase resetting did not occur and all points are arranged on the black lines following the expected period. F, Averaged data from E. The blue lines in D, F represent the linear regression. The colors in A, B are not related to the colors in the other graphs. The diagonal black lines (cophase = 1, old phase) depict the ideal case in which there is not a phase shift produced by the stimuli. A similar description of these diagonal lines was given by Winfree (1987). R indicates the correlation coefficient between old phase and cophase.

  • Figure 3.
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    Figure 3.

    Phase analysis performed on the unitary neuronal activity recorded from the medulla oblongata. A, The same format as Figure 1A but for the firing activity of four medulla oblongata neurons recorded simultaneously with the phrenic nerve activity (PNA). Pink triangles indicate the expected period for the bursting firing of neuron 2. B, Phase-transition graph, constructed with the relationship between the normalized old phase and normalized cophase for the rhythmical firing activity of 22 neurons from the medulla oblongata, as a consequence of the occurrence of fictive scratching episodes. Each color in B is related to each interneuron that produced a phase shift of the respiratory rhythm. In D, each color represents the location of each recorded interneuron. Note the tendency of the points toward a horizontal arrangement (i.e., type 0 resetting). The diagonal black lines (cophase = 1, old phase) depicts the ideal case in which there is not a phase shift produced by the stimuli. C, Pink circles are the averaged data from B, and the vertical lines are the standard deviation. The blue line in C represents the linear regression. D, Schematic drawing of recording sites of rhythmical neurons from the medulla oblongata. R indicates the correlation coefficient between old phase and cophase. FN: Facial Nucleus, Böt: Bötzinger Complex, pre-Böt: pre-Bötzinger Complex, rVRG: rostral Ventral Respiratory Group, cVRG: caudal Ventral Respiratory Group.

  • Figure 4.
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    Figure 4.

    The timing of the phrenic nerve activity before and after scratching episodes in three cats. The black vertical lines illustrate the phase shift in the phrenic nerve activity after the scratching offset and its return (see asterisk) to the expected rhythm. Such return last 29.6, 21.5, and 21.32 s for these animals.

  • Figure 5.
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    Figure 5.

    The timing of phrenic nerve activity and respiratory rhythm imposed by artificial ventilation in three cats as indicated. First trace, phrenic nerve activity (PNA). Second trace, Rectified and integrated phrenic nerve activity. Third trace, Rectified and integrated sound signals recorded with an electret microphone (red traces). Fourth trace, Sound signals (microphone activity, i.e., respiratory activity recorded with an electret microphone). The vertical green lines illustrate the timing between the inspiratory activity and the maximal peak of the rectified and integrated phrenic nerve activity. The beginning of the scratching episode is indicated with the pink line (scratching onset). The end of the scratching episode is illustrated with the blue line (scratching offset). There is the same time separation between the vertical green lines before and after the scratching episode.

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March/April 2019
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Resetting the Respiratory Rhythm with a Spinal Central Pattern Generator
Roberto Meza, Nayeli Huidobro, Mayra Moreno-Castillo, Abraham Mendez-Fernandez, Jorge Flores-Hernandez, Amira Flores, Elias Manjarrez
eNeuro 10 April 2019, 6 (2) ENEURO.0116-19.2019; DOI: 10.1523/ENEURO.0116-19.2019

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Resetting the Respiratory Rhythm with a Spinal Central Pattern Generator
Roberto Meza, Nayeli Huidobro, Mayra Moreno-Castillo, Abraham Mendez-Fernandez, Jorge Flores-Hernandez, Amira Flores, Elias Manjarrez
eNeuro 10 April 2019, 6 (2) ENEURO.0116-19.2019; DOI: 10.1523/ENEURO.0116-19.2019
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Keywords

  • cat
  • phase resetting
  • resetting
  • respiratory
  • scratching CPG
  • spinal cord

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