Stochastic and deterministic dynamics of intrinsically irregular firing in cortical inhibitory interneurons
- University of Cambridge, United Kingdom
- University of Southampton, United Kingdom
- Institute of Experimental Medicine, Hungary
Figures
Figure 1
Irregular-spiking in a population of cortical inhibitory interneurons.
(a) Distribution of Gad2-GFP mouse neurons in the somatosensory cortex (top). Below is the detailed morphology of a typical irregular-spiking interneuron which was filled with neurobiotin. White …
Figure 2 with 1 supplement
Predictability and nonlinearity of interspike interval sequences.
(a) Examples of two contrasting ISI return maps extracted from a regular-spiking cell (blue, mean frequency 9.67 Hz, CVISI = 0.075) and an irregular-spiking cell (red, mean frequency 9.65 Hz, CVISI …
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Figure 2—source data 1
Numerical values for Figure 2d.
- https://doi.org/10.7554/eLife.16475.005
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Figure 2—source data 2
Table showing details of recurrence plot analysis in ten cells.
Nonstationarity is the ratio of the average change in mean ISI in consecutive trials, divided by the standard error of the mean ISI. Time series with nonstationarity > 0.5 were rejected. In five of ten cells, both recurrence and determinism were significant (p< 0.05), only recurrence was significant in a further two cells, while in the three remaining cells, neither recurrence nor determinism were significant.
- https://doi.org/10.7554/eLife.16475.006
Figure 2—figure supplement 1
Significance testing of recurrence and determinism of interspike interval sequences.
(a) Example cross-recurrence plot for the response to one 30 s current step trial against that of the subsequent trial. Threshold (ε) = σISI, embedding dimension m = 4. Each point colored black …
Figure 3
Voltage-gated sodium channel activation is required for noisy subthreshold voltage fluctuations.
(a) The amplitude of subthreshold fluctuations (see example waveform in inset) rises sharply above a threshold membrane potential (≈ −50 mV). Measurements for 23 cells indicated by different …
Figure 4 with 3 supplements
IS neurons express a fast transient outward current with similar kinetics to Kv4.
(a) Whole-cell currents in response to a family of voltage steps from −80 to 0 mV in 5 mV steps. (b) A-type current separated from other outward current components. The remaining step-evoked current …
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Figure 4—source data 1
Numerical values for Figure 4c,d and e.
- https://doi.org/10.7554/eLife.16475.010
Figure 4—figure supplement 1
Irregularity is not diminished by buffering intracellular calcium.
An IS cell recorded with a patch pipette containing normal intracellular solution and stimulated with a steady current stimulus of 150 pA (left) is then repatched with a pipette containing …
Figure 4—figure supplement 2
Fast inactivating outward current is insensitive to TEA (2 mM).
Voltage steps to −10 mV from −80 mV holding potential (n = 6).
Figure 4—figure supplement 3
Gad2-GFP cortical interneurons from primary cultures display the two conductances required for spiking irregularity.
(a) Cells expressed a large, fast-inactivating outward current (n = 4). Steps from −75 mV to 0 mV, held at −80 mV (b) In some cases (n = 3), after measuring spike irregularity, cells were repatched …
Figure 5 with 3 supplements
Injection of synthetic gKt modulates spiking irregularity.
(a) Positive and negative gKt injection in the same cell at the same frequency range (8–10 Hz). While −8.7 nS injection (gmax0, See Materials and methods) caused a reduction in the AHP amplitude and …
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Figure 5—source data 1
Numerical values for Figure 5e and f.
- https://doi.org/10.7554/eLife.16475.015
Figure 5—figure supplement 1
Injecting a shunting conductance at the soma, causing a large reduction in input resistance, modifies the action potential amplitude and shape, and divides down membrane potential fluctuations, but does not regularize firing.
(a) Top: example of control spiking during a 45 pA current step. A linear conductance of 2 nS, reversing at −70 mV was applied during the lower trace (red), and stimulus current increased to 115 pA …
Figure 5—figure supplement 2
Example spike patterns for three different cells with (a) negative gKt conductance injection and three different cells with (b) positive gKt injection, showing decreased and increased irregularity respectively.
https://doi.org/10.7554/eLife.16475.017
Figure 5—figure supplement 3
Effect of pharmacological block of A-type current in IS cells is consistent with the effect of the negative gKt injection.
(a) When 4-AP was locally perfused at 200 or 50 µM, the CVISI decreased by 44% (n = 5), while PhTX 5 µM caused a mean 23% reduction (b, n = 3).
Figure 6 with 1 supplement
Irregular firing in a simple biophysically-based model.
(a) Two-compartment model with Nav, Kv1, Kv3 and gKt-type conductances shows complex spike timing, as a result of unstable subthreshold oscillations and trapping in a nearly-fixed state. = 7 nS, …
Figure 6—figure supplement 1
Statistics and significant recurrence and determinism of time series generated by the computational model.
(a) Example ISI distribution for the stochastic model, with 700 gKt channels, 500 NaP channels, and stimulus current of 83 pA. Note similarity to experimental ISI distribution (Figure 1dii). (b) …
Figure 7
gKt enhances irregularity in deterministic and stochastic biophysical models.
(a) Surface showing the dependence of firing frequency on the total gKt and stimulus current level, colored according to the CV(ISI) of firing. Regions of low CV(ISI) correspond to periodic firing, …
Figure 8
Synchronization to oscillating inhibition is controlled by gKt.
(a) Naturalistic stimulus protocol. The cell was stimulated with a constant step of AMPA conductance (gAMPA, reversing at 0 mV) with added conductance Ornstein-Uhlenbeck noise (standard deviation 2% …
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Figure 8—source data 1
Numerical values for Figure 8b,c,d and e.
- https://doi.org/10.7554/eLife.16475.024
Videos
Video 1
Movie showing dynamics in phase space of the deterministic model.
Corresponds to the trajectory shown in Figure 6b.
Additional files
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Source code 1
- https://doi.org/10.7554/eLife.16475.025
