Figure 7.

DIA Rescues Dysfunction of Pre- and Extra-synaptic α₅-Containing GABA_ARs and Exaggerated Startle Responses in Hyperekplexic Mutant Mice

(A) Trace records, average frequency, and amplitude of GABAergic mIPSCs in brainstem hypoglossal nucleus slices from WT and GlyR α₁ S267Q mutant mice with or without diazepam (10 μM) and/or Xli-093 (1 μM) pre-incubation.

(B) Trace records and average values of bicuculline-sensitive tonic currents (BSTC) in brainstem hypoglossal nucleus slices from WT and GlyR α₁ S267Q mutant mice with or without diazepam (10 μM) and/or Xli-093 (1 μM) pre-incubation.

(C) Hind feet clenching behavior in GlyRα₁^S267Q mutant mice and effect of DIA (i.p. 10 mg/kg) and Xli-093 (intra-brainstem hypoglossal nucleus injection, 5 μg) on this behavior.

(D) Average values of startle responses induced by white noise at 85, 90, and 95 dB in WT (n = 8) and GlyRα₁^S267Q (n = 8) mice.

(E) Average values of startle response activated by white noise at 85 dB in WT and GlyRα₁^S267Q mutant mice with or without diazepam (i.p. 10 mg/kg) and/or Xli-093 (intra-brainstem hypoglossal nucleus injection, 5 μg) treatments.

(F) Correlation analysis of fold increases in startle response, percentage decreases in mIPSC frequency, and amount of mutant α₁ GlyRs co-immunoprecipitated with GABA_ARs in hyperekplexic mutant mice.

All digits within the columns represent numbers of cells or mice measured. Data are represented as mean ± SEM. *p < 0.05, **p < 0.01, ***p < 0.001 based on unpaired t tests; ns, not significant (p > 0.05).