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. Author manuscript; available in PMC: 2025 Aug 25.
Published in final edited form as: J Neurophysiol. 2025 Jun 30;134(1):361–371. doi: 10.1152/jn.00216.2025

Figure 2: EE-induced, NPAS4-dependent reduction in dendritic inhibition from CCK+ inhibitory neurons.

Figure 2:

(A) Confocal image of smFISH in CA1 alveus and stratum oriens (SO) from an SST-Cre+/− mouse injected with AAV8-hDlx-DIO-oChIEF. DAPI (blue), SST mRNA (left brown), Gad2 mRNA (left, white), oChIEF mRNA (middle, yellow). White arrows indicate cells positive for both Gad2 and SST mRNA, red arrows indicate Gad2 only. Scale bar 10 μm. Quantification of specificity (spec.) of expression (percent of oChIEF positive cells that are also Gad2 and SST positive) and percent coverage (Cov.) (percent of Gad2 and SST positive cells that are also oChIEF positive) (B) Cartoon of optical stimulation of SST+ inhibitory terminals in SR with paired voltage clamp recordings from WT (black), and gRNA (red) CA1 pyramidal neurons. oIPSCs (right) recorded from pairs of WT and gRNA-expressing pyramidal neurons from mice housed in EE. Individual data points (grey), geometric mean and SEM (filled circle). Inset: oIPSC traces recorded from WT (black) and gRNA (red) pyramidal neurons. Traces are shown as geometric mean ± SEM. Scale bars: 20 ms by 100% of WT. (ratio paired t-test; n = 15 pairs). (C) As in A, but in CA1 SP and SO with PV-Cre+/− mouse, and PV mRNA (left, green). (D) As in B, but with stimulation of PV+ inhibitory terminals in SR. (n = 10 pairs). (E) As in A and C, but in CA1 SP and SR with NPY-Cre+/− mouse, and NPY mRNA (left, cyan). (F) As in B and D, but with NPY+ inhibitory terminals in SR. (ratio paired t-test; n = 13 pairs). (G) As in A, C, and D, but in CA1 SR with CCK-Cre+/− mouse, and CCK mRNA (left, magenta). (H) As in B, D, ‘n F, but with CCK+ inhibitory terminals in SR (ratio paired t-test; n = 14 pairs) and SE housed geometric mean and SEM (open circle) (ratio paired t-test; n = 15 pairs). (I) gRNA / WT IPSC geometric ratios ± SEM of data shown in B, D, F, and H, with shaded horizontal grey band showing EE-Gad-SR SEM (replotted from Figure 1H). (ratio paired t-test for within-pair comparisons; ANOVA with multiple comparisons for between-genotype comparisons; t-test for CCK+ EE-SE comparison) (J) As in B, D, F, and H, but with CCK+ inhibitory terminals in SP (ratio paired t-test; n =11 pairs). (K) gRNA / WT IPSC geometric ratios ± SEM of data shown in J, with a shaded horizontal grey band showing EE-Gad-SP SEM (replotted from Figure1J).