vu0463271  (Tocris)

Journal: bioRxiv

Article Title: Embryonic exposure to valproic acid and neonicotinoid deteriorates the developmental GABA switch and impairs long-term potentiation in the local circuit of intermediate medial mesopallium of chick telencephalon

doi: 10.1101/2024.09.15.613159

Figure Lengend Snippet: Acute effects of bumetanide (NKCC1 blocker) and VU0463271 (KCC2 blocker) on Vrev and Vrest of VPA-treated and control chicks, respectively. Representative recordings ( A and B ) and population data ( C ). A ) In IMM slice obtained from a VPA-treated chick, Vrev was determined in DNQX-Krebs ( Aa ), and in bumetanide added to the perfusion for 15-20 min ( Ab ); hyperpolarization shift occurred at ΔVrev = -10mV. Replacement of bumetanide with bicuculine completely vanished the voltage-sensitive current, leaving a lasting inward current ( Ac ). B) In the control slice, the addition of VU0463271 to the perfusate Krebs caused a depolarizing shift of Vrev. C) ΔVrev and accompanying ΔVrest are shown in each group; a one-sample t-test was repeated for each.

Article Snippet: The following drugs were applied to the perfusing solution: 6,7-dinitroquinoxaline-2,3-dion (DNQX, 10 μM, Tocris Co.), 1(S),9(R)-(-)-bicuculline methiodide (bicuculline, 10-20 μM, Sigma-Aldrich Co.), VU0463271 (1-10μM, Tocris Co.), bumetanide (20 μg/mL or 55 μM, Tocris Co., in vehicle containing 0.005N NaOH).

Techniques: Control

Journal: bioRxiv

Article Title: Embryonic exposure to valproic acid and neonicotinoid deteriorates the developmental GABA switch and impairs long-term potentiation in the local circuit of intermediate medial mesopallium of chick telencephalon

doi: 10.1101/2024.09.15.613159

Figure Lengend Snippet: Potentiation of excitatory post-synaptic responses was examined in IMM slices. A) Schematic diagram. B) Representative recording of field EPSPs (fEPSPs); superimposed pre-tetanic traces (left, 60 traces for 10 min), post-tetanic traces (middle, 60 traces for 10 min), and traces recorded in DNQX-Krebs (right, 36 traces for 6 min). Pre-synaptic fiber volleys were measured as the amplitude of the initial bi-phasic component just after the local electrical stimulation. The amplitude of the fEPSPs was measured at 0.8 msec (red dashed lines) from the onset point of the DNQX-sensitive component (blue dashed lines). The traces recorded at 5-6 min after the DNQX application yielded the base level (DNQX base, black dashed horizontal line). C) Time course of the fEPSPs before and after the low-frequency tetanic stimulation (5Hz x 300 pulses, downward arrow) after normalization by the pre-tetanic level. Dots and vertical lines indicate the mean and s.e.m. (6 traces x 12 or 11 experiments per min). D) Normalized fEPSP changes induced by tetanic stimulation (LTP, y-axis) was plotted against the fEPSP amplitude recorded pre-tetanus (x-axis) in four groups of slices. See Supplementary Fig. S2 for the acute effects of bumetanide and VU0463271. E) Normalized fEPSPs were compared during the last 5 min (26-30 min post-tetanus, dashed box). Multiple comparison using Dunnett’s method was applied to VPA [35 μmole per egg], IMI [250 μg/egg], and tubocurarine [0.2 mg/egg] against control data; Multiple comparisons revealed significant differences only in IMI. Repeated pairwise comparisons revealed significant differences between control vs. control+VU0463271 (significant by F-test) and between VPA vs VPA+bumetanide (t-test). F) The ratio of the fEPSP amplitude to the pre-synaptic fiber volley was compared among groups. Significant difference was found in VPA and IMI, but not in tubocurarine. Pairwise comparisons revealed significant differences between control vs. control+VU0463271 and between VPA vs. VPA+bumetanide.

Article Snippet: The following drugs were applied to the perfusing solution: 6,7-dinitroquinoxaline-2,3-dion (DNQX, 10 μM, Tocris Co.), 1(S),9(R)-(-)-bicuculline methiodide (bicuculline, 10-20 μM, Sigma-Aldrich Co.), VU0463271 (1-10μM, Tocris Co.), bumetanide (20 μg/mL or 55 μM, Tocris Co., in vehicle containing 0.005N NaOH).

Techniques: Comparison, Control