β-Arrestin-biased proteinase-activated receptor-2 antagonist C781 limits allergen-induced airway hyperresponsiveness and inflammation.

Background And Purpose: Asthma is a heterogenous disease strongly associated with inflammation that has many different causes and triggers. Current asthma treatments target symptoms such as bronchoconstriction and airway inflammation. Despite recent advances in biological therapies, there remains a need for new classes of therapeutic agents with novel, upstream targets.

Outcome-Locked Cholinergic Signaling Suppresses Prefrontal Encoding of Stimulus Associations.

Acetylcholine (ACh) is thought to control arousal, attention, and learning by slowly modulating cortical excitability and plasticity. Recent studies, however, discovered that cholinergic neurons emit precisely timed signals about the aversive outcome at millisecond precision. To investigate the functional relevance of such phasic cholinergic signaling, we manipulated and monitored cholinergic terminals in the mPFC while male mice associated a neutral conditioned stimulus (CS) with mildly aversive eyelid shock (US) over a short temporal gap.