Structure and function differences in the prelimbic cortex to basolateral amygdala circuit mediate trait vulnerability in a novel model of acute social defeat stress in male mice.

Stressful life events are ubiquitous and well-known to negatively impact mental health. However, in both humans and animal models, there is large individual variability in how individuals respond to stress, with some but not all experiencing long-term adverse consequences. While there is growing understanding of the neurobiological underpinnings of the stress response, much less is known about how neurocircuits shaped by lifetime experiences are activated during an initial stressor and contribute to this selective vulnerability versus resilience. We developed a model of acute social defeat stress (ASDS) that allows classification of male mice into "susceptible" (socially avoidant) versus "resilient" (expressing control-level social approach) one hour after exposure to six minutes of social stress. Using circuit tracing and high-resolution confocal imaging, we explored differences in activation and dendritic spine density and morphology in the prelimbic cortex to basolateral amygdala (PL→BLA) circuit in resilient versus susceptible mice. Susceptible mice had greater PL→BLA recruitment during ASDS and activated PL→BLA neurons from susceptible mice had more and larger mushroom spines compared to resilient mice. We hypothesized identified structure/function differences indicate an overactive PL→BLA response in susceptible mice and used an intersectional chemogenetic approach to inhibit the PL→BLA circuit during or prior to ASDS. We found in both cases that this blocked ASDS-induced social avoidance. Overall, we show PL→BLA structure/function differences mediate divergent behavioral responses to ASDS in male mice. These results support PL→BLA circuit overactivity during stress as a biomarker of trait vulnerability and potential target for prevention of stress-induced psychopathology.

Dopamine promotes aggression in mice via ventral tegmental area to lateral septum projections.

Septal-hypothalamic neuronal activity centrally mediates aggressive behavior and dopamine system hyperactivity is associated with elevated aggression. However, the causal role of dopamine in aggression and its target circuit mechanisms are largely unknown. To address this knowledge gap, we studied the modulatory role of the population- and projection-specific dopamine function in a murine model of aggressive behavior. We find that terminal activity of ventral tegmental area (VTA) dopaminergic neurons selectively projecting to the lateral septum (LS) is sufficient for promoting aggression and necessary for establishing baseline aggression. Within the LS, dopamine acts on D2-receptors to inhibit GABAergic neurons, and septal D2-signaling is necessary for VTA dopaminergic activity to promote aggression. Collectively, our data reveal a powerful modulatory influence of dopaminergic synaptic input on LS function and aggression, effectively linking the clinically pertinent hyper-dopaminergic model of aggression with the classic septal-hypothalamic aggression axis.

Familiarity is not notoriety: phenomenological accounts of face recognition.

From a phenomenological perspective, faces are perceived differently from objects as their perception always involves the possibility of a relational engagement (Bredlau, 2011). This is especially true for familiar faces, i.e., faces of people with a history of real relational engagements. Similarly, valence of emotional expressions assumes a key role, as they define the sense and direction of this engagement. Following these premises, the aim of the present study is to demonstrate that face recognition is facilitated by at least two variables, familiarity and emotional expression, and that perception of familiar faces is not influenced by orientation. In order to verify this hypothesis, we implemented a 3 × 3 × 2 factorial design, showing 17 healthy subjects three type of faces (unfamiliar, personally familiar, famous) characterized by three different emotional expressions (happy, hungry/sad, neutral) and in two different orientation (upright vs. inverted). We showed every subject a total of 180 faces with the instructions to give a familiarity judgment. Reaction times (RTs) were recorded and we found that the recognition of a face is facilitated by personal familiarity and emotional expression, and that this process is otherwise independent from a cognitive elaboration of stimuli and remains stable despite orientation. These results highlight the need to make a distinction between famous and personally familiar faces when studying face perception and to consider its historical aspects from a phenomenological point of view.