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Research ArticleNew Research, Sensory and Motor Systems

Analysis of Family Structures Reveals Robustness or Sensitivity of Bursting Activity to Parameter Variations in a Half-Center Oscillator (HCO) Model

Anca Doloc-Mihu and Ronald L. Calabrese
eNeuro 3 August 2016, 3 (4) ENEURO.0015-16.2016; https://doi.org/10.1523/ENEURO.0015-16.2016
Anca Doloc-Mihu
Department of Biology, Emory University, Atlanta, Georgia 30322
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Ronald L. Calabrese
Department of Biology, Emory University, Atlanta, Georgia 30322
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  • Figure 1.
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    Figure 1.

    3D view of the 99,066 realistic HCO instances. Plot of all rHCO instances projected onto the 3D space given by the maximal conductances of IP, IK2, and ILeak. Each point displays a pie chart of the Eleak of all instances from the group having the same values of ḡP, ḡK2, and ḡLeak as the respective projected point. The number of instances projected onto each point in the 3D space is shown by the size of the Eleak pie (as radius). For a better visualization of the points, we applied the natural logarithm to the sizes of the pies.

  • Figure 2.
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    Figure 2.

    The number of instances within the rHCO group and fHCO group vs their period values for each value of ḡh. fHCOs are in blue and rHCOs are in red. Period values were between 1 and 40 s for the fHCOs and between 5 and 15 s for the rHCOs. Plots were obtained using the bar Matlab function (R2014a). Each bar shows the period values within one unit or between [n, n + 1). The bars corresponding to the realistic instances were shifted with 0.3 on the x-axis for better visualization. ḡh values are given as the percentage of the canonical (100%).

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    Figure 3.

    Distribution of h families of rHCOs based on the sequence breakdown of their members. Labels at the margins indicate the beginning (vertical dimension) and end (horizontal dimension)ḡh values of the family sequences. Colors indicate the number of members within the family. The titles of panels show the total number of families [total number of interrupted families plus the number of noninterrupted families (star)]. Numbers under each panel title give the total number of interrupted families (left) and the number of noninterrupted families (right). For each panel, the y-axis indicates the number of families. Bins corresponding to the families having all members with noninterruptedḡh values are marked with an orange star. All panels show data at the same scale.

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    Figure 4.

    Distribution of CaS families of realistic HCOs based on the sequence breakdown of their members. Labels at the margins indicate the beginning (vertical dimension) and end (horizontal dimension)ḡCaS values of the family sequences. Colors indicate the number of members within the family. The titles of panels show the total number of families [total number of interrupted families plus the number of noninterrupted families (star)]. The numbers under each panel title give the total number of interrupted families (left) and the number of noninterrupted families (right). For each panel, the y-axis indicates the number of families. Bins corresponding to the families having all members with noninterruptedḡCaS values are marked with an orange star. Empty panels have been removed. To visualize bins with few families, panels are at different scales.

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    Figure 5.

    Distribution of missing members from h families of rHCOs for eachḡh value. The activity type of the missing members is color coded as shown in the legend.

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    Figure 6.

    Distribution of missing members from P families of rHCOs for each ḡP value. The activity type of the missing members is color coded as shown in the legend.

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    Figure 7.

    Variations of burst characteristics (period and spike frequency) vs ḡh for the realistic HCOs. Lines connect adjacent family members. A, Period vs ḡh for h families with eight members (144 families). All curves are monotonically decreasing. B, Period vs ḡh for h families with four members (4,322 families). For four-member families, regardless of the beginning point, all curves are monotonically decreasing. C, Spike frequency vs ḡh for h families with eight members. Most of the curves are monotonically increasing. D, Spike frequency vs ḡh for h families with four members. For four-member families, regardless of the beginning point, the vast majority of curves are monotonically increasing.

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    Figure 8.

    Sensitivity of period to the variation of ḡh for h families of realistic HCOs. A, Plots of period vs ḡh for h families with eight members (144 families). Lines connect adjacent members of an h family forming a curve. Curves were split into three groups according to their period sensitivity (slopes), as follows: high (steep slopes; 1); medium (medium slopes; 2); and low (shallow slopes; 3). B, Parameter values vs the number of distinct families for all h families with eight members separated into these three groups of sensitivity. The size of each point quantifies how many different families have that parameter value (here, we scale up the sizes by five times for a better display). Black diamond shapes show the median values for each parameter. C, Parameter values vs the number of distinct families from all h families with four members separated into the three groups of sensitivity. For simplicity, plots do not show data for ḡSynG since the graded transmission did not have a significant influence on burst characteristics (see Sensitivity of period to variations of ḡ's, and Sensitivity of spike frequency to variations of ḡ's).

  • Figure 9.
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    Figure 9.

    Examples of ensembles of physiological model instances with large noninterrupted families from which one can choose a canonical model to reflect typical robust physiological activity. Plots show period vs ḡh values for h families of realistic HCOs with lines connecting adjacent family members. The chosen ensemble is highlighted in red. The voltage traces of the two interneurons corresponding to a certain model from the family are shown above their corresponding ḡh values (bigger red circles); each trace is the same amount of time (22 s). Horizontal lines indicate −50 mV for each trace. A1, Ensemble corresponding to a noninterrupted h family with eight members (of 119 families having all other ḡ’s ≠ 0) showing medium-sensitivity slope curve of period vs ḡh. A2, The three selected models give rise to spiking isolated neurons by cutting any synaptic transmission (ḡSynS = 0 and ḡSynG = 0). B1, Ensemble corresponding to a noninterrupted h family with five members (out of 513 noninterrupted families having all other ḡ values ≠0) showing a high-sensitivity slope curve of period vs ḡh. B2, The three selected models give rise to realistic bursting isolated neurons by cutting any synaptic transmission between the two neurons.

Tables

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    Table 1:

    The number of families for each parameter within the realistic HCO group

    One memberTwo membersThree membersFour membersFive membersSix membersSeven membersEight members
    P92,9703,048 (3,048)
    K268,70213,163 (11,836)1,299 (1,223)34 (34)1 (1)
    Leak66,61111,873 (10,305)2,133 (1,569)452 (301)92 (54)7 (6)
    CaS43,50017,851 (13,471)5,263 (3,854)929 (765)67 (63)4 (4)
    SynS38,58816,950 (11,131)6,390 (3,341)1,542 (832)236 (121)10 (7)
    h16,8779,895 (5,545)6,325 (2,525)4,322 (1,411)2,703 (930)1,285 (415)537 (240)144 (144)
    SynG10,5517,047 (2,830)5,086 (1,276)4,124 (865)3,046 (535)1,971 (483)1,061 (448)1,023 (1,023)
    • Families with the same number of members are grouped together. In parentheses, we show the number of noninterrupted families.

    • View popup
    Table 2:

    The number of missing h family members of rHCOs that have functional HCO bursting classified according to the physiological criteria that they fail

    PeriodSpike
    frequency
    Duty cyclePeriod and
    spike frequency
    and duty cycle
    Period
    and spike
    frequency
    Period
    and duty
    cycle
    Spike
    frequency
    and duty cycle
    Two members3,7593,67926,449514963,6914,324
    Three members2,1881,59716,102312881,9231,716
    Four members1,2865989,538221541,087633
    Five members6561954,6432296559216
    Six members162571,6280314637
    Seven members31939300242
    • View popup
    Table 3:

    The number of h family curves of the rHCOs classified according to their (period) sensitivity (curve slopes)

    Three membersFour membersFive membersSix membersSeven membersEight members
    High69068458332312135
    Medium1,0021,23997952823357
    Low4,6332,3991,14143418352
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Analysis of Family Structures Reveals Robustness or Sensitivity of Bursting Activity to Parameter Variations in a Half-Center Oscillator (HCO) Model
Anca Doloc-Mihu, Ronald L. Calabrese
eNeuro 3 August 2016, 3 (4) ENEURO.0015-16.2016; DOI: 10.1523/ENEURO.0015-16.2016

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Analysis of Family Structures Reveals Robustness or Sensitivity of Bursting Activity to Parameter Variations in a Half-Center Oscillator (HCO) Model
Anca Doloc-Mihu, Ronald L. Calabrese
eNeuro 3 August 2016, 3 (4) ENEURO.0015-16.2016; DOI: 10.1523/ENEURO.0015-16.2016
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Keywords

  • analysis
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  • half-center oscillator
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