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Figure 2 | Molecular Brain

Figure 2

From: Weaker control of the electrical properties of cerebellar granule cells by tonically active GABAA receptors in the Ts65Dn mouse model of Down’s syndrome

Figure 2

Unchanged contributions of δ or α6 containing GABA A Rs to the tonic current in Ts65Dn GCs. (A) Extracts of continuous current recordings from a wild-type GC (WT, filled circle) and a Ts65Dn GC (filled triangle) held at −70 mV under three conditions: before drug application (control), in the presence of the δ-selective agonist, THIP (300 nM, dashed horizontal bar) and in THIP (300 nM) plus SR95531 (10 μM, white horizontal bar). Current amplitude is normalised by cell capacitance. Dashed lines: current remaining after block of GABAARs with SR95531. The tonic GABAAR-current, measured as the difference between currents in the presence and absence of SR95531, was enhanced by THIP. The increase was associated with an increase in noise. (B) Summary of tonic GABAAR current-densities in the absence (con.) and presence of THIP in individual wild-type (*p < 0.0001, Student’s paired t test) and Ts65Dn (*p < 0.0001, Student’s paired t test) GCs. (C) Box plot of current-densities in THIP expressed relative to control values (dashed line). The enhancement by THIP was not different in wild-type and Ts65Dn cells (*p = 0.9625, Mann–Whitney U test). (D) Recordings arranged as in A, showing a decrease in tonic current and noise caused by the α6-selective antagonist, furosemide (100 μM, dashed horizontal bars). Control recordings were made in the presence of DMSO (horizontal lines) at a concentration (0.1%) equal to that present during the application of furosemide. (E). Tonic GABAAR current-densities in the absence (con.) and presence of furosemide (fur.) in wild-type (*p = 0.0005, Mann Whitney U test) and Ts65Dn (*p = 0.0007, Student’s paired t test) GCs. (F) Box plot of current-densities in furosemide relative to control values (dashed line). The fractional inhibition by furosemide was not different in wild-type and Ts65Dn cells (*p = 0.7520, Mann–Whitney U test).

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