The mouse dorsal peduncular cortex encodes fear memory.

The rodent medial prefrontal cortex (mPFC) is functionally organized across the dorsoventral axis, where dorsal and ventral subregions promote and suppress fear, respectively. As the ventral-most subregion, the dorsal peduncular cortex (DP) is hypothesized to function in fear suppression. However, this role has not been explicitly tested. Here, we demonstrate that the DP paradoxically functions as a fear-encoding brain region and plays a minimal role in fear suppression. By using multimodal analyses, we demonstrate that DP neurons exhibit fear-learning-related plasticity and acquire cue-associated activity across learning and memory retrieval and that DP neurons activated by fear memory acquisition are preferentially reactivated upon fear memory retrieval. Further, optogenetic activation and silencing of DP fear-related neural ensembles drive the promotion and suppression of freezing, respectively. Overall, our results suggest that the DP plays a role in fear memory encoding. Moreover, our findings redefine our understanding of the functional organization of the rodent mPFC.

The resilience of adolescent male rats to acute stress-induced delayed anxiety is age-related and glucocorticoid release-dependent.

Studies investigated how stressful experiences modulate physiological and behavioral responses and the consequences of stress-induced corticosterone release in anxiety-like behavior. Adolescence is crucial to brain maturation, and several neurobiological changes in this period lead individuals to increased susceptibility or resilience to aversive situations. Despite the effects of stress in adults, information about adolescents' responses to acute stress is lacking. We aimed to understand how adolescence affects acute stress responses. Male adolescent rats (30 days old) were 2 h restrained, and anxiety-like behaviors were measured immediately or 10 days after stress in the elevated plus-maze (EPM) and the light-dark box (LDB) tests. To verify the importance of CORT modulation in stress-induced anxiety, another group of rats was treated, 30 min before restraint, with metyrapone to blunt the stress-induced CORT peak and tested immediately after stress. To show that stress effects on behavior were age-dependent, another set of rats was tested in two different periods - early adolescence (30 days old) and mid-adolescence (40 days old) and were treated or not with metyrapone before the stress session and tested immediately or ten days later in the LDB test. Only early adolescent male rats were resilient to delayed anxiety-like behavior in EPM and LDB tests. Metyrapone treatment increased the rats' exploration immediately and ten days after stress. These data suggest a specific age at which adolescent rats are resilient to the delayed effects of acute restraint stress and that the metyrapone treatment has long-term behavioral consequences.

Exploring the light/dark box test: Protocols and implications for neuroscience research.

BACKGROUND: Knowledge on the neurobiological systems underlying psychiatric disorders has considerably evolved due to findings on basic research using animal models. Anxiety-like behaviors in rodents are widely explored in neuroethological apparatuses, such as the light-dark box (LDB) test through different protocols, which have been shown to influence the behavioral outcomes and probably the activation of the hypothalamic-pituitary-adrenal (HPA) axis. NEW METHOD: Adult male Wistar rats were submitted to LDB in different room illumination conditions (25/0, 65/0 and/or 330/0 lux), initial positioning in the LDB compartments and previous stressful experience in the Elevated Plus Maze (EPM) or restraint stress (RS). Rats' behavior (exploratory and risk assessment) was registered during a 15 min period, divided into blocks of 5 min RESULTS: Exploration of the lit compartment decreased in higher luminosity condition, as after positioning rats in the dark compartment or previous exposure to the EPM, while low luminosity increased exploration of the LDB. No differences were observed on serum corticosterone in all groups and experimental conditions. COMPARISON WITH EXISTING METHODS: Light intensity and test duration influenced exploration of the LDB jeopardizing the anxiolytic/anxiogenic effects. Low light intensity increased exploration, while high intensity decreased it. These results suggest that 65/0 lux is a neutral condition to investigate possible anxiolytic/anxiogenic effects of drugs and/or exposure to previous aversive stimuli as the EPM. CONCLUSIONS: Different factors impact on exploratory and risk assessment behaviors which may be related to safety maximization behavior. Unraveling how different factors affect behavior may be a crucial step towards understanding its expression and the contributions on advances in the physiopathology 1 and treatment of psychiatric disorders.

Imipramine attenuates anxiety- and depressive-like effects of acute and prolonged ethanol-abstinence in male rats by modulating SERT and GR expression in the dorsal hippocampus.

AIMS: Considering that serotoninergic agents attenuate symptoms of anxiety and are used to treat depression, we investigated whether subchronic treatment with imipramine, a serotonin/noradrenaline reuptake inhibitor, would prevent the anxiogenic-like behaviour induced by acute and/or chronic ethanol withdrawal. We also investigated whether those changes were related to the disfunctioning of hypothalamic-pituitary-adrenal (HPA) axis and serotonergic neurotransmission. MAIN METHODS: 264 Male Wistar rats were treated with ethanol 6% (vol./vol.) for 21 days. Acute ethanol withdrawal was induced by abrupt discontinuation of treatment and sustained for 48 h. Protracted abstinence was sustained for an additional period of 21 days. Behavioural tests included the Elevated Plus Maze (EPM) or Light/Dark Box (LDB) after acute abstinence, and the Forced Swim Test (FST) after protracted abstinence. Imipramine (15 mg/kg, i.p.) was administered 24, 19 and 1 h before EPM or LDB tests. KEY FINDINGS: Acute abstinence decreased exploration of the open arms of the EPM, without changing exploration of LDB. Additionally, chronic abstinent rats displayed more time immobile in the FST, when compared to control animals. These effects were attenuated by imipramine treatment, without changing basal response. Imipramine prevented protracted abstinence -induced decrease in glucocorticoid receptor (GR) and serotonin transporter (SERT) expression in the dorsal hippocampus. SIGNIFICANCE: Our findings indicate that chronic ethanol withdrawal affects the hippocampal serotonergic system by decreasing serotonin transporter expression. It also disturbs the HPA axis functioning through an imbalance on GR and mineralocorticoid (MR) expression.