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. Author manuscript; available in PMC: 2023 Jun 12.
Published in final edited form as: Nat Neurosci. 2022 Dec 12;26(1):64–78. doi: 10.1038/s41593-022-01214-2

Fig. 4. Sleep-wake dependent EGABAA determines how easily a cortical neuron is recruited to spike.

Fig. 4

a. Cell-attached recordings were used to measure the spiking probability of S1 L5 pyramidal neurons in response to the stimulation of two independent L2/3 input pathways, across different inter-stimulus delays. b. Spiking activity for different inter-stimulus delays in a neuron from the ZT3 low sleep pressure condition, the ZT15 higher sleep pressure condition, ZT3 in the presence of VU, or ZT15 in the presence of bumetanide. Downward vertical arrows indicate the time of the second stimulus and individual spikes are highlighted with shading. c. Normalized spike probability for different inter-stimulus delays and conditions (grey: 8 neurons, 8 slices, 3 animals; black: 10 neurons, 10 slices, 3 animals; red: 8 neurons, 8 slices, 2 animals; blue: 6 neurons, 6 slices, 2 animals) Color-coding as in ‘b’. d. The synaptic integration window for spiking (defined as the time constant of spike probability data in ‘c’) for each of the experimental conditions. Color-coding as in ‘b’. Integration windows are shorter at ZT3 compared to ZT15 (grey versus black; ***p<0.001, Tukey-Kramer post-test; q=6.575; d=2.22), are decreased following NKCC1 blockade at ZT15 (blue versus black; ***p<0.001, Tukey-Kramer post-test; q=6.145; d=2.07), and increased following VU at ZT3 (red versus grey; *p<0.05, Tukey-Kramer post-test; q=4.26; d=1.66). Multiple groups comparison p<0.0001, one-way ANOVA. e. Simple network model to compare neuronal recruitment as a function of [Cl-]i and therefore EGABAA. The model comprised 400 glutamatergic neurons and 100 GABAergic neurons, each receiving synchronous oscillatory input to simulate ON and OFF periods. f. Raster plots of excitatory neuron spiking activity in response to a 1 Hz input, for three different EGABAA values. g. Depolarized EGABAA values are associated with greater neuronal recruitment during ON periods (spike rate normalized to OFF periods). h. EGABAA values affect neuronal recruitment for lower frequencies of oscillatory input. Data represent mean ± sem. All tests are two sided.