Suppressing the Maintenance of Information in Working Memory Alters Long-term Memory Traces.

The sensory recruitment hypothesis conceptualizes information in working memory as being activated representations of information in long-term memory. Accordingly, changes made to an item in working memory would be expected to influence its subsequent retention. Here, we tested the hypothesis that suppressing information from working memory, which can reduce short-term access to that information, may also alter its long-term neural representation. We obtained fMRI data (n = 25; 13 female / 12 male participants) while participants completed a working memory removal task with scene images as stimuli, followed by a final surprise recognition test of the examined items. We applied a multivariate pattern analysis to the data to quantify the engagement of suppression on each trial, to track the contents of working memory during suppression, and to assess representational changes afterward. Our analysis confirms previous reports that suppression of information in working memory involves focused attention to target and remove unwanted information. Furthermore, our findings provide new evidence that even a single dose of suppression of an item in working memory can (if engaged with sufficient strength) produce lasting changes in its neural representation, particularly weakening the unique, item-specific features, which leads to forgetting. Our study sheds light on the underlying mechanisms that contribute to the suppression of unwanted thoughts and highlights the dynamic interplay between working memory and long-term memory.

Ventral tegmental area GABA neurons mediate stress-induced blunted reward-seeking in mice.

Decreased pleasure-seeking (anhedonia) forms a core symptom of depression. Stressful experiences precipitate depression and disrupt reward-seeking, but it remains unclear how stress causes anhedonia. We recorded simultaneous neural activity across limbic brain areas as mice underwent stress and discovered a stress-induced 4 Hz oscillation in the nucleus accumbens (NAc) that predicts the degree of subsequent blunted reward-seeking. Surprisingly, while previous studies on blunted reward-seeking focused on dopamine (DA) transmission from the ventral tegmental area (VTA) to the NAc, we found that VTA GABA, but not DA, neurons mediate stress-induced blunted reward-seeking. Inhibiting VTA GABA neurons disrupts stress-induced NAc oscillations and rescues reward-seeking. By contrast, mimicking this signature of stress by stimulating NAc-projecting VTA GABA neurons at 4 Hz reproduces both oscillations and blunted reward-seeking. Finally, we find that stress disrupts VTA GABA, but not DA, neural encoding of reward anticipation. Thus, stress elicits VTA-NAc GABAergic activity that induces VTA GABA mediated blunted reward-seeking.

A Novel Method for Chronic Social Defeat Stress in Female Mice.

Historically, preclinical stress studies have often omitted female subjects, despite evidence that women have higher rates of anxiety and depression. In rodents, many stress susceptibility and resilience studies have focused on males as one commonly used paradigm-chronic social defeat stress-has proven challenging to implement in females. We report a new version of the social defeat paradigm that works in female mice. By applying male odorants to females to increase resident male aggressive behavior, we find that female mice undergo repeated social defeat stress and develop social avoidance, decreased sucrose preference, and decreased time in the open arms of the elevated plus maze relative to control mice. Moreover, a subset of the female mice in this paradigm display resilience, maintaining control levels of social exploration and sucrose preference. This method produces comparable results to those obtained in male mice and will greatly facilitate studying female stress susceptibility.