Amylin Modulates a Ventral Tegmental Area-to-Medial Prefrontal Cortex Circuit to Suppress Food Intake and Impulsive Food-Directed Behavior.

Background: A better understanding of the neural mechanisms regulating impaired satiety to palatable foods is essential to treat hyperphagia linked with obesity. The satiation hormone amylin signals centrally at multiple nuclei including the ventral tegmental area (VTA). VTA-to-medial prefrontal cortex (mPFC) projections encode food reward information to influence behaviors including impulsivity.

Liposaccharide-induced sustained mild inflammation fragments social behavior and alters basolateral amygdala activity.

Rationale: Conditions with sustained low-grade inflammation have high comorbidity with depression and anxiety and are associated with social withdrawal. The basolateral amygdala (BLA) is critical for affective and social behaviors and is sensitive to inflammatory challenges. Large systemic doses of lipopolysaccharide (LPS) initiate peripheral inflammation, increase BLA neuronal activity, and disrupt social and affective measures in rodents.

The medial orbitofrontal cortex governs reward-related circuits in an age-dependent manner.

Nucleus accumbens (NAc) neurons integrate excitatory inputs from cortical and limbic structures, contributing to critical cognitive functions, including decision-making. As these afferents mature from adolescence through adulthood, incoming signals to the NAc may summate differently between age groups. Decision-making evaluates both reward and risk before action selection, suggesting an interplay between reward- and risk-related circuits.

Medial orbitofrontal cortex and nucleus accumbens mediation in risk assessment behaviors in adolescents and adults.

Risk assessment behaviors are necessary for gathering risk information and guiding decision-making. Risky decision-making heightens during adolescence, possibly as a result of low risk awareness and an increase in sensitivity to reward-associated cues and experiences. Higher adolescent engagement in high-risk behaviors may be, in part, due to developing circuits that contribute to risk assessment behaviors.

Developmental Shifts in Amygdala Activity during a High Social Drive State.

Amygdala abnormalities characterize several psychiatric disorders with prominent social deficits and often emerge during adolescence. The basolateral amygdala (BLA) bidirectionally modulates social behavior and has increased sensitivity during adolescence. We tested how an environmentally-driven social state is regulated by the BLA in adults and adolescent male rats.

Shifts in Medial Orbitofrontal Cortex Activity from Adolescence to Adulthood.

Adolescents are characterized by a propensity for risky and impulsive behaviors, likely due to immature frontostriatal circuits. The medial orbitofrontal cortex (MO) is linked to risk and reward prediction during decision-making. Identifying age-dependent differences in MO activity and its inputs to downstream regions can elucidate the neural substrates that permit the transition from high-risk adolescent behaviors to increased risk assessment in adulthood.

Fear Learning Enhances Prefrontal Cortical Suppression of Auditory Thalamic Inputs to the Amygdala in Adults, but Not Adolescents.

Adolescence is characterized by increased susceptibility to the development of fear- and anxiety-related disorders. Adolescents also show elevated fear responding and aversive learning that is resistant to behavioral interventions, which may be related to alterations in the circuitry supporting fear learning. These features are linked to ongoing adolescent development of medial prefrontal cortical (PFC) inputs to the basolateral amygdala (BLA) that regulate neural activity and contribute to the refinement of fear responses.

Repeated stress induces a pro-inflammatory state, increases amygdala neuronal and microglial activation, and causes anxiety in adult male rats.

A link exists between immune function and psychiatric conditions, particularly depressive and anxiety disorders. Psychological stress is a powerful trigger for these disorders and stress influences immune state. However, the nature of peripheral immune changes after stress conflicts across studies, perhaps due to the focus on few measures of pro-inflammatory or anti-inflammatory processes.