Heterozygous Clptm1 KO increases phasic and tonic inhibition in adult mice. A, Expression levels of Clptm1 and GABA_AR γ2 subunits in WT mouse brain were detected and compared at different developmental stages using Western blotting. Expression of Clptm1 increased from P1 to P14, plateaued between P14 and P21, and declined after P21. In contrast, expression of GABA_AR γ2 increased from P1 to P42. n = 3 mice; Clptm1, p = 0.0034; GABA_AR γ2, p < 0.0001, one-way ANOVA. B, mIPSC recordings were collected from CA1 pyramidal neurons at P42–49. Heterozygous Clptm1 KOfirst mice had increased mIPSC amplitude with no change in mIPSC frequency. WT, n = 10 cells from two mice; KOfirst/+, n = 10 cells from two mice; for cumulative probability of interevent interval, p = 0.7699, K-S test; for cumulative probability of amplitude, p < 0.0001, K-S test; for frequency, p = 0.2975, t test; for amplitude, ***p = 0.0009, t test. C, Quantification of averaged mIPSC events showed no significant change in decay kinetics. p = 0.8363, Mann–Whitney test. D, Recordings were collected from CA1 pyramidal neurons at P43–50. Bicuculline (20 µM) was added into the recording solution to record tonic currents. GABA_AR-mediated tonic currents were significantly increased in Clptm1 heterozygous KOfirst mice compared with WT mice. WT, n = 8 cells from three mice; KOfirst/+, n = 9 cells from four mice; ***p = 0.0003, t test.