Fig. 4: GluA1 deletion disrupts stimulus-specific habituation of light cue evoked dopamine responses. | Molecular Psychiatry

Fig. 4: GluA1 deletion disrupts stimulus-specific habituation of light cue evoked dopamine responses.

From: Glutamatergic dysfunction leads to a hyper-dopaminergic phenotype through deficits in short-term habituation: a mechanism for aberrant salience

Fig. 4

a Representation of the trial structure in the task. On each trial two stimuli were presented 30 s apart. The identity of stimulus 2 in each pair was either the same or different to stimulus 1. Mice have been shown to reduce attention to stimulus 2 when it is the same as stimulus 1, but attention remains high when stimulus 2 is different to stimulus 1 [24, 25]. This selective attentional effect is stimulus specific habituation. Magazine activity in WT (b) and KO (c) mice immediately prior to stimulus presentation (Baseline), during the first stimulus of a pair (First) and during the second stimulus of a pair depending on whether it is the same or a different stimulus to the first (Same and Different). Suppression of this magazine directed behavior during stimulus presentation, relative to baseline, provides a measure of a behavioral orienting response [24]. Planned comparisons revealed that WT mice showed significantly less suppression to the Same than the Different stimulus (F1, 44.01 = 3.18, p = 0.04), and significantly more suppression to the Different stimulus than Baseline (F1, 44.01 = 4.54, p = 0.04; all remaining F1, 44.01 < 2.06, ps > 0.16) suggesting that suppression of magazine behavior to the light stimuli habituated in a stimulus specific manner. In contrast there was no evidence of habituation to the light stimuli in the KO mice (no significant differences between any Periods, all F1, 44.01 < 3.18, ps > 0.08). This pattern of behavior replicates earlier findings [24], although the genotype by period interaction did not reach statistical significance (Genotype F1, 14.95 = 1.44, p = 0.25, Period F3, 44.11 = 2.08, p = 0.117, Genotype × Period F3, 44.11 = 1.33, p = 0.28). Average DA release to the LED light stimulus when it was stimulus 1 (d), and when it was stimulus 2 for the WT (e) and Gria1−/− mice (f). Inset bar graphs depict the peak DA estimated at 1 s post stimulus onset. All error bars represent ± standard error of the mean.

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