Event-related oscillations as risk markers in genetic mouse models of high alcohol preference

Abstract

Mouse models have been developed to simulate several relevant human traits associated with alcohol use and dependence. However, the neurophysiological substrates regulating these traits remain to be completely elucidated. We have previously demonstrated that differences in the event-related potential (ERP) responses can be found that distinguish high-alcohol preferring from low alcohol preferring mice that resemble differences seen in human studies of individuals with high and low risk for alcohol dependence. Recently, evidence of genes that affect event-related oscillations (EROs) and the risk for alcohol dependence has emerged, however, to date EROs have not been evaluated in genetic mouse models of high and low alcohol preference. Therefore, the objective of the present study was to characterize EROs in mouse models of high (C57BL/6 [B6] and high alcohol preference 1 [HAP-1] mice) and low (DBA/2J [D2] and low alcohol preference-1 [LAP-1] mice) alcohol preference. A time-frequency representation method was used to determine delta, theta and alpha/beta ERO energy and the degree of phase variation in these mouse models. The present results suggest that the decrease in P3 amplitudes previously shown in B6 mice, compared to D2 mice, is related to reductions in evoked delta ERO energy and delta and theta phase locking. In contrast, the increase in P1 amplitudes reported in HAP-1 mice, compared to LAP-1 mice, is associated with increases in evoked theta ERO energy. These studies suggest that differences in delta and theta ERO measures in mice mirror changes observed between groups at high- and low-risk for alcoholism where changes in EROs were found to be more significant than group differences in P3 amplitudes, further suggesting that ERO measures are more stable endophenotypes in the study of alcohol dependence. Further studies are needed to determine the relationship between expression of these neurophysiological endophenotypes and the genetic profile of these mouse models.

Figure 1

Time-frequency representation of evoked delta, theta and alpha/beta bands energy distribution of rare stimuli in the frontal and parietal cortices in B6 and D2 mice. Time-frequency responses of evoked theta (e) and alpha/beta (b, d, f) bands energy distribution to rare stimuli in B6 (A) and D2 (B) mice in the frontal cortex. Time-frequency responses of evoked delta (a, c) and alpha/beta (b, f) bands energy distribution to rare stimuli in B6 (C) and D2 (D) mice in the parietal cortex. Time-frequency ROI windows used were 0 – 50 ms, 50 – 350 ms and 350 – 800 ms (white squares).

Figure 2

Mean amplitude values of ERO energy for delta bands in response to standard, rare and noise stimuli in the frontal and parietal cortices. B6 mice showed attenuation of post-stimulus decrease in delta ERO energy in the 0–50 ms time window in response to standard and rare tones in the parietal cortex (B). B6 mice showed lower delta ERO energy than D2 mice in the 50–350 ms time window in response to standard and rare tones in the parietal cortex (D). * = Significant differences between B6 and D2 mice (P < 0.05).

Figure 3

Mean amplitude values of ERO energy for evoked alpha/beta band in response to standard, rare and noise tones in frontal and parietal cortices. B6 mice showed lower ERO energy than D2 mice in the alpha/beta band in response to standard and rare tones in the frontal cortex (A: 0–50 ms; C: 50–350 ms; E: 350–800 ms). B6 mice showed lower ERO energy than D2 mice in the alpha/beta band in response to standard (B: 0–50 ms) and rare (B: 0–50 ms; F: 350–800 ms) in the parietal cortex. In contrast, Bt mice showed higher ERO energy than D2 mice in response to noise tones in the frontal (A: 050 ms) and parietal (B: 0–50 ms) cortices. * = Significant differences between B6 and D2 mice (P<0.05).

Figure 4

Time-frequency representation of evoked delta, theta and alpha/beta bands PLI distribution of rare stimuli in the parietal cortex in B6 and D2 mice. Time-frequency responses of evoked delta (a, c) and theta (b, d) bands PLI distribution to rare stimuli in B6 (A) and D2 (B) mice in the parietal cortex. Time-frequency ROI windows used were 0 – 50 ms and 50 – 350 ms (white squares).

Figure 5

Time-frequency representation of evoked delta, theta and alpha/beta bands energy distribution of rare stimuli in the frontal cortex in HAP-1, LAP-1 and HS/Ibg mice. Time-frequency responses of evoked theta band energy distribution to rare stimuli in HAP-1 (A), LAP-1 (B) and HS/Ibg (C) mice in the frontal cortex. Time-frequency ROI windows used was 50 – 350 ms (white squares).

Figure 6

Mean amplitude values of ERO energy for theta bands in response to standard, rare and noise stimuli in the frontal cortex. LAP-1 mice showed lower ERO energy than HAP-1 mice in the 350–800 ms time window in the theta band in response to rare tones. LAP-1 mice showed lower ERO energy than HS/Ibg mice in response to standard, rare and noise tones. * = Significant differences between HAP-1 and LAP-1 mice (P < 0.05). & = Significant differences between HS/Ibg and LAP-1 mice (P < 0.05).