KO of Clptm1 increases inhibitory synaptic strength. A, Clptm1 flox/flox cultured hippocampal neurons were transduced with AAV-GFP or AAV-GFP-Cre at 3 DIV. Lysates were collected at 14 DIV for Western blotting. No signal for Clptm1 was detected in the AAV-GFP-Cre–transduced sample. B, C, Clptm1 flox/flox cultured hippocampal neurons were transfected with YFP or Cre + DIO-GFP at 0 DIV. mIPSC recordings and immunostaining were performed at 14 DIV. B, Neurons were immunostained live using anti-GABA_AR γ2 antibody, followed by fixation and immunostaining for VGAT and the dendritic marker MAP2. KO of Clptm1 significantly increased synaptic surface γ2 intensity without changing postsynaptic γ2 puncta number. Scale bar represents 10 µm. n = 31 cells each from two independent experiments; for puncta intensity, ****p < 0.0001, t test; for puncta number, p = 0.0592, t test. C, KO of Clptm1 significantly increased mIPSC amplitude without changing mIPSC frequency. n = 19 cells for YFP and 20 cells for Cre + DIO-GFP from two independent experiments; for cumulative probability of interevent interval, p = 0.5819, K-S test; for cumulative probability of amplitude, p < 0.0001, K-S test; for frequency, p = 0.7584, Mann–Whitney test; for amplitude, *p = 0.0448, t test. D, Clptm1flox/flox mice were injected with AAV-GFP or AAV-Cre + AAV-DIO-GFP at P0. mIPSC recordings were performed from GFP-positive CA1 pyramidal neurons at P15–19. KO of Clptm1 increased mIPSC amplitude without changing mIPSC frequency. AAV-GFP, n = 24 cells from three mice; AAV-Cre + AAV-DIO-GFP, n = 18 cells from four mice; for cumulative probability of interevent interval, p = 0.8900, K-S test; for cumulative probability of amplitude, p < 0.0001, K-S test; for frequency, p = 0.9476, t test; for amplitude, ****p < 0.0001, Mann–Whitney test. E, Quantification of averaged mIPSC events from cultured hippocampal neurons in C showed no significant changes in decay kinetics. p = 0.4842, t test. F, Quantification of averaged mIPSC events from acute hippocampal slices in D showed no significant changes in decay kinetics. p = 0.1313, t test.