1. Volume 97, Issue 6, Pages 1315-1326.e3 (March 2018)
Differential Control of Axonal and Somatic Resting Potential by Voltage-Dependent Conductances in Cortical Layer 5 Pyramidal Neurons 
Wenqin Hu, Bruce P. Bean 
Neuron 
Volume 97, Issue 6, Pages e3 (March 2018)
DOI: /j.neuron
Copyright © 2018 Elsevier Inc. Terms and Conditions

2. Neuron 2018 97, 1315-1326.e3DOI: (10.1016/j.neuron.2018.02.016)
Copyright © 2018 Elsevier Inc. Terms and Conditions

3. Figure 1
The Resting Potential Is More Negative in the Axon of Layer 5 Pyramidal Neurons than in the Soma or Proximal Dendrite
(A) Schematic of whole-cell recording from the proximal dendrite, soma, or axon blebs of layer 5 pyramidal neurons.
(B) Resting membrane potential in simultaneous dual recordings from soma (black filled circles) and axon of the same neuron (red filled circles). Bars: mean ± SEM from these measurements (n = 6).
(C) Population measurements of resting potential in the dendrite (blue), soma (black), and axon (red).
(D) Mean ± SEM of resting potential measured in the dendrite (n = 6; mean of 20 ± 4 μm from soma), soma (n = 31), and axon (n = 32; mean of 91 ± 11 μm from soma). ∗∗∗p ≤
Neuron  , e3DOI: ( /j.neuron )
Copyright © 2018 Elsevier Inc. Terms and Conditions

4. Figure 2
Kv7 Channels Strongly Influence Axonal but Not Somatic Resting Potential
(A) Left: effect of 20 μM XE-991 on resting potential measured in the soma (black) or axon (red; recording from different cell, 206 μm from soma). Right: effect of retigabine (10 μM) on somatic and axonal (124 μm from soma) resting membrane potentials (different cells).
(B) Collected results for effects of XE-991 and retigabine on somatic (left) and axonal (right) resting potential measured during wash-on of agents.
(C) Mean ± SEM of somatic and axonal resting potential before and after wash-on of the agents (soma: XE-991, n = 6; retigabine, n = 4; axon: XE-991, n = 5, mean of 136 ± 21 μm from soma; retigabine, n = 5, mean of 109 ± 28 μm from soma).
(D) Mean ± SEM of resting potentials measured immediately after breakthrough in control (soma, n = 10; axon, n = 19, mean of 79 ± 16 μm from soma), in presence of 20 μM XE-991 (soma, n = 10; axon, n = 10, 108 ± 12 μm from soma), or in presence of 10 μM retigabine (soma, n = 5; axon, n = 4, 111 ± 16 μm from soma). Measurements in same series of slices used in (B) and (C).
(E) Voltage-clamp measurements of Kv7 current in whole-cell recordings from soma (top) and axon (bottom). Currents were evoked by a 20 mV/s ramp from –95 to +5 mV before and after application of 20 μM XE-991.
(F) Mean ± SEM of maximum outward current evoked by the 20 mV/s ramp in the soma and in axon blebs at various distances from the soma (from left to right, n = 6, 7, 5, 7). Shaded area represents XE-991-sensitive current. ∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001; NS, non-significant.
Neuron  , e3DOI: ( /j.neuron )
Copyright © 2018 Elsevier Inc. Terms and Conditions

5. Figure 3
Subthreshold TTX-Sensitive Persistent Sodium Current Exerts a Depolarizing Influence on the Resting Potential of the Axon
(A) Top: ramp-evoked current recorded in a cell body before (black) and after (gray) application of 1 μM TTX. Bottom: voltage dependence of TTX-sensitive current recorded in the soma (black).
(B) Top: ramp-evoked current in a recording from an axon before (black) and after (gray) application of TTX. Bottom: voltage dependence of TTX-sensitive current in the axon (red).
(C) Mean ± SEM of resting potential in recordings from soma (black) and axon (red) in the absence or presence of TTX (from left to right, n = 31, 32 [mean 91 ± 12 μm from soma], 8, and 13 [mean 109 ± 12 μm from soma]). ∗p ≤ 0.05; ∗∗p ≤ 0.01; ∗∗∗p ≤ 0.001; NS, non-significant.
Neuron  , e3DOI: ( /j.neuron )
Copyright © 2018 Elsevier Inc. Terms and Conditions

6. Figure 4
Steady-State T-type Ca Current Influences Resting Potential of Both Soma and Axon
(A) Ramp-evoked currents before and application of 2 μM TTA-A2 in recordings from soma (top) and axon (bottom).
(B) Voltage dependence of steady-state TTX-A2-sensitive current in soma (black) and axon (red).
(C) Mean ± SEM of somatic (black) or axonal (red) resting potential in the absence or presence of TTA-A2 (from left to right, n = 31, 32 [mean 91 ± 12 μm from soma], 10, and 10 [mean 165 ± 19 μm from soma]). ∗p ≤ 0.05; ∗∗∗p ≤
Neuron  , e3DOI: ( /j.neuron )
Copyright © 2018 Elsevier Inc. Terms and Conditions

7. Figure 5
HCN Current Strongly Influences Both Somatic and Axonal Resting Potential despite Being Minimal in the Axon
(A) Top, whole-cell currents evoked by a slow ramp (20 mV/s) from −105 to −55 mV before and after application of 50 μM ZD-7288 in recordings from the soma (top) and axon (bottom).
(B) Voltage dependence of steady-state ZD-7288-sensitive current recorded in soma (black) and axon (red).
(C) Mean ± SEM of somatic (black) or axonal (red) resting potential in the absence or presence of ZD-7288 and cocktails of multiple blockers. From left to right, n = 31, 32 (mean 91 ± 12 μm from soma), 13, 11 (mean 142 ± 15 μm from soma), 11, 19 (mean 114 ± 10 μm from soma), 5, and 5 (mean 145 ± 25 μm from soma).
(D) Schematic of recording configuration from blebs attached to axon trunk (left) or isolated blebs with severed axon stem (right).
(E) Mean ± SEM of resting potential in the absence or presence of ZD-7288 recorded in attached (red) or isolated (black) axon blebs. From left to right, n = 32, 11, 14, and 6. ∗p ≤ 0.05; ∗∗∗p ≤
Neuron  , e3DOI: ( /j.neuron )
Copyright © 2018 Elsevier Inc. Terms and Conditions

8. Figure 6
Summary of the Influence of Channel Inhibitors on Resting Potential in Different Neuronal Compartments
Mean ± SEM; blue: dendrite, black: soma, red: axon. From left to right, n = 6, 31, 32, 10, 10, 8, 13, 10, 10, 13, 11, 11, and 19.
Neuron  , e3DOI: ( /j.neuron )
Copyright © 2018 Elsevier Inc. Terms and Conditions

9. Figure 7 Asymmetric Coupling of Voltage from Soma to Axon
(A) Dual recording from the soma (black) and axon bleb (red). Current steps (500 ms) were injected into either soma or the axon, while the membrane voltage was recorded at both sites simultaneously.
(B) Somatic (black) and axonal (red) input resistance plotted versus distance from soma (dashed line, linear fit, slope = 1.49 ± 0.15, R = 0.83).
(C) The transmission ratio of voltage change measured in axon with current injected into soma (black) or measured in soma with current injected into axon (red). Transmission ratio was measured as voltage change relative to that at point of injection.
Neuron  , e3DOI: ( /j.neuron )
Copyright © 2018 Elsevier Inc. Terms and Conditions

10. Figure 8
Model of Voltage-Dependent Channels Controlling Somatic and Axonal Resting Potential in Layer 5 Neurons
(A) Left: inferred distribution of conductances influencing somatic and axonal resting potential in layer 5 pyramidal neurons. Right: normalized current-voltage relationship (in the steady state) for each conductance used in the model. “K-leak / Pass” corresponds to the combination of a background non-voltage dependent potassium-selective leak conductance with reversal potential at −105 mV together with a background non-selective cation conductance with a reversal potential of 0 mV. The combined leak conductance has a reversal potential of −88 mV.
(B) Predictions of model for input resistance in soma (black) and in axon (red) at various distances from soma; dashed line from experimental data in Figure 7.
(C) Predictions of the transmission ratio of voltage change measured in axon with current injected into soma (black) or measured in soma with current injected into axon (red). Dashed lines from experimental data in Figure 7.
(D) Predictions of model for somatic (black) and axonal (red) resting potential in control and after inhibition of individual or all voltage-dependent conductances. Solid columns show results from a model with axon bleb, open columns show results from a model with full intact axon. Dashed lines from experimental data shown in Figure 6.
(E) Schematic summary of control of resting potential in soma and axon by voltage-dependent conductances controlling one another by steady-state voltage. The schematic is simplified in showing only the conductances that have major influences in each compartment.
Neuron  , e3DOI: ( /j.neuron )
Copyright © 2018 Elsevier Inc. Terms and Conditions