Fig. 2: Functional KCC2 in perinatal interneurons drives an early developmental shift in the polarity of interneuronal GABAergic signaling. | Nature Communications

Fig. 2: Functional KCC2 in perinatal interneurons drives an early developmental shift in the polarity of interneuronal GABAergic signaling.

From: Functional KCC2 expression marks an evolutionarily conserved population of early-maturing interneurons in the perinatal cortex

Fig. 2

a Illustration of electrode placement in somatosensory barrel-field cortex (SIBF) layer 5 interneurons in perinatal mice, and gramicidin perforated-patch recording configuration. b I–V plots and example traces from gramicidin recordings of interneurons (INs) and principal neurons (PNs) of layer 5 c Quantification of GABAergic reversal potential (EGABA), GABAergic driving force (DFGABA), resting membrane potential (RMP), intracellular chloride (Cl−) calculated using the GHK equation, and an RMP vs EGABA plot; from PNs and INs. n = 56 INs from 10 animals and 21 PNs from 6 animals. ****p ≤ 0.0001: unpaired two-tailed t-test and two-tailed Mann–Whitney test. d Population-level slice recordings demonstrate the overall impact of the drug VU0463271 on KCC2 inhibition. Quantification of EGABA, DFGABA, and RMP from INs with and without application of VU. n = 15 INs with and without VU application from 3 animals. *p = 0.02, two-tailed Mann–Whitney test ****p ≤ 0.0001: unpaired two-tailed t-test and two-tailed Mann–Whitney test. e Same quantifications as in D, in PNs with and without application of VU0463271. n = 8 PNs without VU application and 8 PNs with VU application from 3 animals. Unpaired two-tailed t-test. f Quantification of pairwise recordings of INs and PNs showing cell-specific responses to VU in a KCC2-expression dependent manner, from a subset of INS and PNs in E. INs show heterogeneous sensitivity to VU, while all PNs are insensitive to VU application. *p = 0.0382, paired two-tailed t test. n = 6 INs, n = 5 PNs. g Quantification of EGABA, DFGABA, RMP, and Cli; from KCC2+ and KCC2- interneurons. n = 29 KCC2+ INs and 19 KCC2- INs, 7 animals. **p = 0.0049, ****p = <0.0001, **p = 0.0030; unpaired two-tailed t-tests. h Quantification of EGABA, DFGABA, RMP across P0-P2 reveals no significant variance. n = 4, 3, and 3 animals and 25, 17, and 14 INs at P0, P1, and P2, respectively. One-way ANOVA, unpaired two-tailed t-test. Data presented as mean values ± SEM. Source data provided as a Source data file. Panel a created in BioRender. Srinivasan, R. (2025) https://BioRender.com/a5jwigh. Supplementary data 10 for detailed statistics.

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