Article Figures & Data
Figures
- Figure 1.
Acute alcohol exposure alters BLA network activity differently in male and female C57BL/6J mice. A, Representative targeting of BLA LFP recordings. B, Acute alcohol exposure paradigm consisted of LFP recordings during baseline (60 min), vehicle injection (0.9% saline, i.p.; 60 min), and a treatment injection (0.9% saline or 1 g/kg alcohol, i.p.; 60 min). This dose was determined through a dose response (Extended Data Fig. 1-2). C, D, Representative male spectrogram of normalized beta power (15–30 Hz; C) and representative female spectrogram of normalized gamma power (40–70 Hz; D) from acute alcohol exposure. E, F, Average normalized beta power in males (E) and average normalized gamma power in females (F) during acute injections of vehicle and alcohol (1 g/kg, i.p.; Extended Data Fig. 1-2, dose response). Dots represent the mean, and the shaded region represents the SEM. G, H, Normalized power area for vehicle/alcohol acute exposure in males (n = 11; G) and females (n = 8; H). #p < 0.05 vs baseline; *p < 0.05, **p < 0.01 vs vehicle. Acute vehicle exposure does not alter BLA network activity in C57BL/6J mice (Extended Data Fig. 1-1). Summaries of ANOVA and multiple-comparison tests can be found in Extended Data Tables 1-1 and 1-2.
- Figure 2.
Acute alcohol exposure produces effects in Gabrd−/− mice similar to those in female C57BL/6J mice. A, C, Representative male (A) and female (C) spectrogram of normalized gamma power from acute alcohol exposure. B, D, Normalized power area for vehicle/alcohol acute exposure in male (n = 9; B) and female (n = 8; D) Gabrd−/− mice. #p < 0.05 versus baseline; *p < 0.05, **p < 0.01 versus vehicle. Acute vehicle exposure does not alter BLA network activity in Gabrd−/− mice (Extended Data Fig. 2-1). Summaries of ANOVA and multiple-comparison tests can be found in Extended Data Tables 2-1 and 2-2.
- Figure 3.
Repeated alcohol exposure exaggerates BLA network modulation in male C57BL/6J mice. A, Experimental paradigm (left) of the repeated alcohol exposure procedure in male C57BL/6J and Gabrd−/− mice of BLA LFP recordings during baseline (60 min) and vehicle or alcohol injections (0.9% saline or 1 g/kg alcohol, i.p.; 60 min) over 5 d. BEC measurements (right) of male C57BL/6J mice (n = 6) taken 15 min after alcohol exposure (1 g/kg, i.p.) on days 1, 2, and 5 of exposure. ***p < 0.0001. B, Repeated alcohol exposure paradigm (left) for female C57BL/6J and Gabrd−/− mice, which includes the acute alcohol exposure and the repeated alcohol exposure as day 2 (first day) to 5 (last day). Justification for using day 2 instead of day 1 is in Extended Data Figure 3-3. BEC measurements (right) of female C57BL/6J mice (n = 5) taken 15 min after alcohol exposure (1 g/kg, i.p.) on days 1, 2, and 5 of exposure. C–F, Change in the effect of alcohol on the first and last days of exposure in male (first day, n = 8; last day, n = 6; C) and female (first day, n = 10; last day, n = 8; D) C57BL/6J mice and male (first day, n = 8; last day, n = 8; E) and female (first day, n = 8; last day, n = 7; F) Gabrd−/− mice. *p < 0.05 versus first exposure. Repeated vehicle exposure does not change BLA network activity (Extended Data Fig. 3-1). Baseline network activity is modulated by repeated alcohol exposure in male C57BL/6J mice (Extended Data Fig. 3-2). Summaries of ANOVA and multiple-comparison tests can be found in Extended Data Tables 3-1 and 3-2.
- Figure 4.
δ-GABAAR and sex-dependent effects of repeated alcohol exposure on BLA network activity. A, B, Comparison between male C57BL/6J and Gabrd−/− mice in the response to alcohol on the first day (A) and last day (B) of exposure. C, D, Comparison between male and female C57BL/6J mice in the response to alcohol on the first day (C) and the last day (D) of exposure. *p < 0.05, **p < 0.01. Repeated alcohol has δ-GABAAR and sex-dependent effects on baseline network activity (Extended Data Fig. 4-1).
- Figure 5.
Repeated alcohol exposure reduces δ-GABAAR expression on PV interneurons in female C57BL/6J mice. A, B, Integrated density of PV immunoreactivity (A) and δ expression (B) on PV interneurons in naive male (cell, n = 224; animal, n = 4) and female (cell, n = 202; animal, n = 4) C57BL/6J mice. C, Representative images from male and female C57BL/6J mice who received repeated administration of vehicle or alcohol. D, E, Integrated density of PV immunoreactivity (D) and δ expression (E) on PV interneurons in the BLA of male (vehicle: cell, n = 112; animal, n = 3; alcohol: cell, n = 97; animal, n = 3) and female (vehicle: cell, n = 117; animal, n = 3; alcohol: cell, n = 169; animal, n = 3) C57BL/6J mice who received repeated administrations of vehicle or alcohol. *p < 0.05, **p < 0.01, ****p < 0.0001.
Extended Data
Table 1-1
Summary of ANOVAs for acute alcohol experiments in C57BL/6J mice. Download Table 1-1, DOCX file.
Table 1-2
Summary of multiple-comparison tests for acute alcohol experiments in C57BL/6J mice. Download Table 1-2, DOCX file.
Table 2-2
Summary of multiple-comparison tests for acute alcohol experiments in Gabrd– /– mice. Download Table 2-2, DOCX file.
Table 3-2
Summary of multiple-comparison tests for repeated alcohol experiments. Download Table 3-2, DOCX file.
Figure 1-1
Acute vehicle exposure does not alter BLA network activity in C57BL/6J mice. A, B, Normalized power area for vehicle/vehicle acute exposure in male (n = 13; A) and female (n = 6; B) mice. C, D, Power spectral density of baseline, vehicle, and 1 g/kg alcohol injection over 0–80 Hz in male mice (C) and female mice (D). #p < 0.05, ##p < 0.01 versus baseline. Download Figure 1-1, TIF file.
Figure 1-2
Effects of an alcohol dose response on BLA network states. A, Power area difference of 2–5, 6–12, and 15–30 Hz frequency ranges across alcohol doses in male C57BL/6J mice (0.5, n = 8; 1.0, n = 8; 1.5, n = 4; 2.0, n = 7). B–F, Shaded region indicates doses that caused high immobility in mice. Normalized power area for vehicle/alcohol exposure across doses for 2–5 Hz (B), 6–12 Hz (C), 15–30 Hz (D), 40–70 Hz (E), and 80–120 Hz (F). *p < 0.05, **p < 0.01 versus vehicle. Download Figure 1-2, TIF file.
Figure 2-1
Acute vehicle exposure does not alter BLA network activity in Gabrd– /– mice. A, B, Normalized power area for vehicle/vehicle exposure in male mice (n = 8; A) and female mice (n = 7; B). Download Figure 2-1, TIF file.
Figure 3-2
Repeated alcohol exposure modulates baseline network activity in male C57BL/6J mice. A, B, Change in baseline on the first and last day of alcohol exposure in male (A) and female (B) C57BL/6J mice and male (C) and female (D) Gabrd– /– mice. *p < 0.05. Download Figure 3-2, TIF file.
Figure 3-3
Effects of acute alcohol exposure on day 1 (acute) and day 5 do not differ in female Gabrd– /– mice. A, Normalized power area of alcohol injections during the acute alcohol injection and day 2 in female C57BL/6J mice (n = 10). B, Normalized power area of alcohol injections during the acute alcohol injection and day 2 in female Gabrd– /– mice. B, Normalized power area of alcohol injections during acute alcohol injection and day 5 in female Gabrd– /– mice. **p < 0.01. Download Figure 3-3, TIF file.
Table 2-1
Summary of ANOVAs for acute alcohol experiments in Gabrd– /– mice. Download Table 2-1, DOCX file.
Figure 3-1
Repeated vehicle exposure does not change BLA network activity in C57BL6/J and Gabrd– /– mice. A–D, Power area difference between vehicle and baseline for the first and last days of exposure in male (first day, n = 4; last day, n = 3; A) and female (first day, n = 5; last day, n = 6; B) C57BL/6J mice and male (first day, n = 4; last day, n = 4; C) and female (first day, n = 7; last day, n = 7; D) Gabrd– /– mice. Download Figure 3-1, TIF file.
Table 3-1
Summary of ANOVAs for repeated alcohol experiments. Download Table 3-1, DOCX file.
Figure 4-1
δ-GABAARs and sex-dependent effects of baseline network modulation after repeated alcohol. A, B, Comparison between male C57BL/6J and Gabrd– /– mice in the change in baseline on the first day (A) and last day (B) of exposure. C, D, Comparison between male and female C57BL/6J mice in the change in baseline on the first day (C) and last day (D) of exposure. *p < 0.05. Download Figure 4-1, TIF file.
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