PMC

Decreased input resistance in Up states during seizures resembles deep anesthesia. (A, B) An example of voltage response to negative current pulses in M2 cortical pyramidal layer 5 neuron in deep anesthesia and seizure epochs. Top traces, Vm; Middle traces, expanded from top traces where time segments are indicated by horizontal colored lines, with Up states (red), Down states (blue); Bottom traces, 10 Hz 50 ms 100pA square negative (hyperpolarizing) current pulses. Action potentials are truncated at top. (C) Example of Up and Down states free of negative pulses in deep anesthesia epoch from the same cell. (D, E) Mean Vm response for pulses from example traces (A, B) in deep anesthesia and seizure epochs. Voltage deflection in Up states is smaller than Down states. To facilitate comparison in D, E, voltages at the end of baseline period (just before start of hyperpolarizing current pulse) have been aligned vertically to remove the offset from the mean Up and Down state traces. Voltages including the vertical displacement are shown in A, B. (F) Comparison of input resistance in Up and Down states during seizure and deep anesthesia epochs. The mean input resistance in Up states (red lines) was lower than in Down states (blue lines) (deep down vs. deep up; n = 12 neurons, ^****P < 0.0001, paired, 2-tailed t-test; seizure down vs. seizure up; n = 12 neurons, ^***P = 0.0005, paired 2-tailed t-test). There is no difference between Up states and Down states in seizures versus deep anesthesia. Seizure up versus deep up, n = 12 neurons, P = 0.86 (NS), paired 2-tailed t-test; seizure down versus deep down; n = 12 neurons, P = 0.64 (NS), paired 2-tailed t-test.

(A) Median DOWN epoch duration plotted against median UP epoch duration for each dataset color-coded by subfield of whole-cell target. Population averages are marked by the interrupted lines (UP = 2.43 s, DOWN = 2.37 s). Open circles mark the datasets for which dura resection occurred 3 days before the experiment (no same day anesthesia, UP = 2.24 s, DOWN = 2.25 s). The medians of these four marked datasets were not significantly different from the rest (Wilcoxon rank sum test, p>0.05). (B) Distributions of DOWN (black) and UP (gray) epoch durations pooled across all datasets. Epochs are detected with 250 ms resolution, so the curves at durations shorter than that are affected. Distributions are nearly exponential with similar means (UP = 3.06 s, DOWN = 3.25 s) and standard deviations (UP = 3.57 s, DOWN = 3.48 s). Outliers (15/13053 UP and 2/13139 DOWN epochs with durations longer than 60 s) were excluded. The blue and red lines show the distributions for datasets with no same day anesthesia (means: UP = 2.11 s, DOWN = 3.15 s; standard deviations: UP = 1.95 s, DOWN = 3.11 s).

Examples of reconstructions of up- and downward FM sweeps. (A) Neuron with strong correlation values for the Channel reconstructions, but weaker correlations for the Delay and Onset reconstructions. From left to right: responses to 80 dB SPL tones, averaged subthreshold response to fast FM sweep at 80 dB SPL (“Data”), Delay, Onset, and Channel reconstructions. Correlation values during stimulation: 0.11 (up Delay), −0.11 (down Delay), −0.34 (up Onset), −0.12 (down Onset), 0.97 (up Channel), 0.61 (down Channel). Selectivity error: 1.78 mV (Delay), 3.28 mV (Onset), 1.34 mV (Channel). Resting membrane potential was −71 mV. (B) Neuron with strong correlations for upward sweeps. Correlation values during stimulation: 0.89 (up Delay), 0.10 (down Delay), 0.96 (up Onset), 0.06 (down Onset), 0.97 (up Channel) and 0.67 (down Channel). Selectivity error: 2.10 mV (Delay), 2.94 mV (Onset), 1.66 mV (Channel). Resting membrane potential was −74 mV. (C) Neuron with variable correlations for the types of reconstructions. Correlation values during stimulation: 0.46 (up Delay), −0.0.33 (down Delay), 0.47 (up Onset), 0.56 (down Onset), −0.19 (up Channel), 0.79 (down Channel). Selectivity error: 2.94 mV (Delay), 4.78 mV (Onset), 0.13 mV (Channel). Resting membrane potential was −68 mV. (D) Neuron showing good correlations for most reconstruction methods. Correlation values during stimulation: 0.92 (up Delay), 0.34 (down Delay), 0.83 (up Onset), 0.70 (down Onset), 0.85 (up Channel) and 0.91 (down Channel). Selectivity error: 1.37 mV (Delay), 1.61 mV (Onset), 1.95 mV (Channel). Resting membrane potential was −58 mV.

Over-represented custom categories in differentially expressed genes in Col and myc2/3/4 under different experimental condition. For each custom category, all genes enriched at P < 0.05. “Col up” and “Col down” columns indicate the over-represented custom category in up- and down-regulated genes, respectively, compared to Col under high R/FR. “myc2/3/4 up” and “myc2/3/4 down” columns indicate the over-represented custom category in up- and down-regulated genes, respectively, compared to Col. ABA up or ABA down, abscisic acid up- or down-regulated; ACC up or ACC down, 1-aminocyclopropane-1-carboxylic acid up- or downregulated; IAA up or IAA down, indole-3-acetic acid (IAA) up- or downregulated; MJ up or MJ down, methyl jasmonate (MJ) up- or down-regulated; MYC2/3/4 up or MYC2/3/4 down, up- or down-regulated by MYC234 genes; PIF target, PIF target genes; SA up or SA down, salicylic acid up- or down-regulated.