PMC

Trains of simulated synaptic stimuli trigger increase in input resistance, which accumulates and decays slowly as a function of frequency and amplitude of the input train. A, Top (schematic), Input resistance was probed 150 ms before and 10 ms after a 1 s, 500 Hz train of sEPSCs using short hyperpolarizing test pulses (10 ms duration, −300 pA amplitude). EPSC amplitude was adjusted to produce EPSPs of ∼9 mV. Voltage responses to the input resistance probes exhibit increases in amplitude as a result of the trains of sEPSCs (middle). Expanded view of prestimulus and poststimulus input resistance measurements produced a 28% increase in input resistance in this example. B, Input resistance changes are linearly related to both frequency and amplitude of EPSP trains. Top, R_N changes induced by a train of 9 mV EPSPs of varying frequency. Linear fit (dotted line), 4.5%/100 Hz. Bottom, R_N changes induced by a 500 Hz train of variable amplitude. Linear fit (dotted line), 4.6%/mV. There is significant variation across cells for the increase in input resistance. Because the data for change of input resistance as a function of frequency and amplitude were obtained from different cells, the increase in input resistance for comparable frequency and amplitude in B are somewhat different. C, Long trains resulted in an AHP at the end of trains (top). The AHP was <1 mV (n = 5) for trains up to 500 Hz (bottom). D, The increase in input resistance is gradual and biexponential. Subthreshold EPSP trains of 9 mV were delivered at either 500 Hz (open circles, n = 5) or 250 Hz (open squares, n = 4) and varied in duration between 10 and 2000 ms (schematic: dotted inset). Input resistance was measured 10 ms after the train. Time constants for 500 Hz train are 45.1 ± 10.1 and 915.9 ± 215 ms and for 250 Hz train are 74.8 ± 34.7 and 1642.3 ± 1940 ms, respectively. E, The input resistance changes last for hundreds of milliseconds. Subthreshold 500 Hz EPSP trains of 9 mV were delivered for either 2000 ms (open circles, n = 9) or 200 ms (open squares, n = 5), whereas the posttrain input resistance was measured at varying intervals after train (schematic: dotted inset). The time constants of the decay of the input resistance increase for 200 ms train are 24.1 ± 5.4 and 231.5 ± 57.3 ms, whereas for 2000 ms train they are 36.6 ± 1.9 and 440.9 ± 28.7 ms. F, Voltage responses of trains (left) in normal ACSF [control (Ctl): top], I_h block (middle) in the presence of 50 μm ZD7288 (ZD), and I_K-LVA block [80 nm DTX-K (DTX)]. Right traces, Expanded view of first four responses for control, ZD7288, and DTX-K conditions. G, H, Summary of group data showing the sensitivity of input resistance changes (G) and AHP (H) in control, I_h (n = 6), and I_K-LVA blockers (n = 9).

Simulations showing the relationship among the EPSP, the input resistance, and the synaptic location. A: schematic drawings showing the position of activated synapses (shown by dots) and the averaged EPSPs. In the compartment model, 10 areas were assigned as follows: area 0 (soma), area 1 (within 5 μm from the soma), area 2 (5–50 μm away from the soma), area 3 (50–100 μm away from the soma), area 4 (100–150 μm away from the soma), area 5 (150–200 μm away from the soma), area 6 (200–250 μm away from the soma), area 7 (250–300 μm away from the soma), area 8 (300–350 μm away from the soma), and area 9 (>350 μm away from the soma). Approximate boundaries are shown by broken lines. A1: synaptic positions and the averaged EPSPs in the area 2. The EPSPs were from the different simulations in which the input resistance was changed by reducing the membrane resistance of the model appropriately. The input resistances were as follows (in MΩ): 333.7, 301.9, 269.7, 236.9, 203.3, 168.1, 130.1, and 84.9. The largest EPSP corresponds to the simulation of the model having the largest input resistance and vice versa. A2: synaptic positions and the averaged EPSPs in the area 5. A3: synaptic positions and the averaged EPSPs in the area 8. B1: 3-dimensional (3D) plot showing the relationship among the EPSP amplitude, the input resistance and the synaptic location (area). B2: 3D plot showing the relationship among the normalized EPSP amplitude, the input resistance, and the synaptic location (area). B3: relationship between the input resistance and the amplitude of EPSP. The normalized amplitudes of EPSPs are plotted against the normalized input resistances, and the relationships in 9 areas are superimposed. The number near each trace shows the area number. The experimental data of uEPSPs shown in are also superimposed. LPP: black; MPP: red; MCF: blue. Each symbol shows the mean value and the error bar indicates SD. C1: 3D plot showing the relationship among the decay time constant (τ) of EPSP, the input resistance and the synaptic location (area). C2: 3D plot showing the relationship among the normalized τ of EPSP, the input resistance, and the synaptic location (area). C3: relationship between the input resistance and the τ of EPSP. The normalized τ of EPSPs are plotted against the normalized input resistances, and the relationships in 9 areas are superimposed. The uppermost trace is a relationship at area 1 and the lowermost one is that at area 9. The values calculated from the uEPSP data shown in are also superimposed. LPP: black; MPP: red; MCF: blue. Each symbol shows the mean value and the error bar indicates SD.

Injecting artificial g_h affects differentially membrane input resistance of DCN fusiform quiet and active neurons. (A) Example of the effect of injecting 5 nS of artificial g_h on the response to hyperpolarizing current in a fusiform neuron. (B) Summary of the effect of injecting 5 nS of artificial g_h on the membrane input resistance of DCN fusiform active neurons. ^∗p < 0.05. (C) Summary of the effect of injecting 5 nS of artificial g_h on the membrane input resistance of DCN fusiform quiet neurons. (D) Effect of 5 nS artificial g_h on the immediate membrane input resistance of fusiform neurons. (E) Effect of application of increasing artificial g_h on the normalized membrane input resistance of quiet and active neurons (n = 7 each). ^∗∗p < 0.01; ^∗∗∗p < 0.005.

(a) Percentage change in input resistance (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl₂ (Kruskal-Wallis rank sum test, p = 0.47 for input resistance at soma; p = 0.19 for input resistance at ~125 μm; p = 0.29 for input resistance at ~250 μm). (b) Percentage change (mean ± SEM) in input resistance after blocking KA channels using BaCl₂ plotted as a function of membrane potential. (c,d) Same as (a,b) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.54 for input resistance at soma; p = 0.40 for input resistance at ~125 μm; p = 0.55 for input resistance at ~250 μm). (e) Percentage change in f_R (represented as quartiles) measured at different membrane potentials and for various recording locations after blocking KA channels using BaCl₂ (Kruskal-Wallis rank sum test, p < 0.05 for f_R at soma; p < 0.001 for f_R at ~125 μm; p < 0.01 for f_R at ~250 μm; followed by Mann-Whitney U test, *p < 0.05). (f) Percentage change (mean ± SEM) in f_R after blocking KA channels using BaCl₂ plotted as a function of membrane potential. (g,h) Same as (e,f) but employing 3,4-DAP to block KA channels (Kruskal-Wallis rank sum test, p = 0.12 for f_R at soma; p = 0.30 for f_R at ~125 μm; p = 0.12 for f_R at ~250 μm).