A dual-pathway architecture enables chronic stress to disrupt agency and promote habit formation.

Chronic stress can change how we learn and, thus, how we make decisions. Here we investigated the neuronal circuit mechanisms that enable this. Using a multifaceted systems neuroscience approach in male and female mice, we reveal a dual pathway, amygdala-striatal neuronal circuit architecture by which a recent history of chronic stress disrupts the action-outcome learning underlying adaptive agency and promotes the formation of inflexible habits.

Stress, associative learning, and decision-making.

Exposure to acute and chronic stress has significant effects on the basic mechanisms of associative learning and memory. Stress can both impair and enhance associative learning depending on type, intensity, and persistence of the stressor, the subject's sex, the context that the stress and behavior is experienced in, and the type of associative learning taking place. In some cases, stress can cause or exacerbate the maladaptive behavior that underlies numerous psychiatric conditions including anxiety disorders, obsessive-compulsive disorder, post-traumatic stress disorder, substance use disorder, and others.

Neurotensin neurons in the extended amygdala control dietary choice and energy homeostasis.

Obesity is a global pandemic that is causally linked to many life-threatening diseases. Apart from some rare genetic conditions, the biological drivers of overeating and reduced activity are unclear. Here, we show that neurotensin-expressing neurons in the mouse interstitial nucleus of the posterior limb of the anterior commissure (IPAC), a nucleus of the central extended amygdala, encode dietary preference for unhealthy energy-dense foods.

Sex-Specific Stress-Related Behavioral Phenotypes and Central Amygdala Dysfunction in a Mouse Model of 16p11.2 Microdeletion.

Background: Substantial evidence indicates that a microdeletion on human chromosome 16p11.2 is linked to neurodevelopmental disorders, including autism spectrum disorder (ASD). Carriers of this deletion show divergent symptoms besides the core features of autism spectrum disorder, such as anxiety and emotional symptoms.

A Central Amygdala-Globus Pallidus Circuit Conveys Unconditioned Stimulus-Related Information and Controls Fear Learning.

The central amygdala (CeA) is critically involved in a range of adaptive behaviors, including defensive behaviors. Neurons in the CeA send long-range projections to a number of extra-amygdala targets, but the functions of these projections remain elusive. Here, we report that a previously neglected CeA-to-globus pallidus external segment (GPe) circuit plays an essential role in classical fear conditioning.

Interactions between hERG and KCNQ1 α-subunits are mediated by their COOH termini and modulated by cAMP.

KCNQ1 and hERG encode the voltage-gated potassium channel α-subunits of the cardiac repolarizing currents I(Ks) and I(Kr), respectively. These currents function in vivo with some redundancy to maintain appropriate action potential durations (APDs), and loss-of-function mutations in these channels manifest clinically as long QT syndrome, characterized by the prolongation of the QT interval, polymorphic ventricular tachycardia, and sudden cardiac death. Previous cellular electrophysiology experiments in transgenic rabbit cardiomyocytes and heterologous cell lines demonstrated functional downregulation of complementary repolarizing currents.