Haploinsufficiency of GABAA Receptor-Associated Clptm1 Enhances Phasic and Tonic Inhibitory Neurotransmission, Suppresses Excitatory Synaptic Plasticity, and Impairs Memory

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Figure 3.
Figure 3.

Heterozygous Clptm1 KO increases phasic and tonic inhibition in juvenile mice. A, mIPSC recordings were collected from CA1 pyramidal neurons at P15–18. Both male and female heterozygous Clptm1 KOfirst mice had increased mIPSC amplitude without changing mIPSC frequency. Male WT, n = 17 cells from two mice; male KOfirst/+, n = 17 cells from two mice; female WT, n = 16 cells from two mice; female KOfirst/+, n = 16 cells from three mice; for cumulative probability of interevent interval, male p = 0.5621; female p = 0.8013, K-S test; for cumulative probability of amplitude, male p < 0.0001; female p < 0.0001, K-S test; for frequency, sex p = 0.0122; genotype p = 0.9585; sex and genotype interaction p = 0.5792, two-way ANOVA; for amplitude, sex p = 0.0165; genotype p < 0.0001; sex and genotype interaction p = 0.8885; two-way ANOVA and **p < 0.01 post hoc Tukey's test. B, Quantification of averaged mIPSC events showed no significant changes in decay kinetics. Sex p = 0.1833; genotype p = 0.1044; sex and genotype interaction p = 0.0512, two-way ANOVA. C, Recordings were collected from CA1 pyramidal neurons at P15–18. Bicuculline (20 µM) was added into the recording solution to record tonic currents. Both male and female heterozygous Clptm1 KOfirst mice had increased GABAAR-mediated tonic currents. Male WT, n = 13 cells from three mice; male KOfirst/+, n = 11 cells from two mice; female WT, n = 16 cells from four mice; female KOfirst/+, n = 16 cells from four mice; sex p = 0.5698; genotype p < 0.0001; sex and genotype interaction p = 0.2267, two-way ANOVA and **p < 0.01; ***p < 0.001 post hoc Tukey's test. D, eIPSCs were recorded from CA1 pyramidal cells while stimulating the stratum radiatum with increasing multiples of threshold intensity at P16–18. eIPSCs were significantly elevated at stimulation intensities greater than four times threshold in heterozygous KOfirst mice. WT, n = 10 cells from three mice; KOfirst/+, n = 12 cells from two mice; stimulation intensity p < 0.0001; genotype p < 0.0001; stimulation intensity and genotype interaction p < 0.001; two-way ANOVA and *p < 0.05; ***p < 0.001 post hoc Sidak's test. E, No differences were detected in the paired-pulse ratio of eIPSCs recorded from CA1 pyramidal cells with multiple interpulse intervals at P16–18. WT, n = 10 cells from three mice; KOfirst/+, n = 12 cells from two mice; interpulse interval p = 0.5239; genotype p = 0.4711; interpulse interval and genotype interaction p = 0.9999, two-way ANOVA.

  1. The Journal of Neuroscience vol. 44 no. 32
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