Habenula orphan G-protein coupled receptors in the pathophysiology of fear and anxiety

The phasic emotion, fear, and the tonic emotion, anxiety, have been conventionally inspected in clinical frameworks to epitomize memory acquisition, storage, and retrieval. However, inappropriate expression of learned fear in a safe environment and its resistance to suppression is a cardinal feature of various fear-related disorders. A significant body of literature suggests the involvement of extra-amygdala circuitry in fear disorders. Consistent with this view, the present review underlies incentives for the association between the habenula and fear memory. G protein-coupled receptors (GPCRs) are important to understand the molecular mechanisms central to fear learning due to their neuromodulatory role. The efficacy of a pharmacological strategy aimed at exploiting habenular-GPCR desensitization machinery can serve as a therapeutic target combating the pathophysiology of fear disorders. Originating from this milieu, the conserved nature of orphan GPCRs in the brain, with some having the highest expression in the habenula can lead to recent endeavors in understanding its functionality in fear circuitry.