Sex-biased neural encoding of threat discrimination in nucleus accumbens afferents drives suppression of reward behavior.

Learning to predict threat is essential, but equally important-yet often overlooked-is learning about the absence of threat. Here, by recording neural activity in two nucleus accumbens (NAc) glutamatergic afferents during aversive and neutral cues, we reveal sex-biased encoding of threat cue discrimination. In male mice, NAc afferents from the ventral hippocampus are preferentially activated by threat cues.

Ventral Hippocampal Afferents to Nucleus Accumbens Encode Both Latent Vulnerability and Stress-Induced Susceptibility.

Background: Stress is a major risk factor for depression, but not everyone responds to stress in the same way. Identifying why certain individuals are more susceptible is essential for targeted treatment and prevention. In rodents, nucleus accumbens (NAc) afferents from the ventral hippocampus (vHIP) are implicated in stress-induced susceptibility, but little is known about how this pathway might encode future vulnerability or specific behavioral phenotypes.

Wiring the depressed brain: optogenetic and chemogenetic circuit interrogation in animal models of depression.

The advent of optogenetics and chemogenetics has revolutionized the study of neural circuit mechanisms of behavioral dysregulation in psychiatric disease. These powerful technologies allow manipulation of specific neurons to determine causal relationships between neuronal activity and behavior. Optogenetic tools have been key to mapping the circuitry underlying depression-like behavior in animal models, clarifying the contribution of the ventral tegmental area, nucleus accumbens, medial prefrontal cortex, ventral hippocampus, and other limbic areas, to stress susceptibility.

In Vivo Fiber Photometry Reveals Signature of Future Stress Susceptibility in Nucleus Accumbens.

Recognizing why chronic stress causes only a subset of individuals to become depressed is critical to understanding depression on a basic level and, also, to developing treatments that increase resilience. Stress-induced alterations in the activity of reward-related brain regions, such as the nucleus accumbens (NAc), are linked to the pathophysiology of depression. However, it has been difficult to determine if differences in stress susceptibility are pre-existing or merely an effect of chronic stress.