Dynorphin/Kappa-Opioid Receptor System Modulation of Cortical Circuitry

Cortical circuits control a plethora of behaviors, from sensation to cognition. The cortex is enriched with neuropeptides and receptors that play a role in information processing, including opioid peptides and their cognate receptors. The dynorphin (DYN)/kappa-opioid receptor (KOR) system has been implicated in the processing of sensory and motivationally-charged emotional information and is highly expressed in cortical circuits. This is important as dysregulation of DYN/KOR signaling in limbic and cortical circuits has been implicated in promoting negative affect and cognitive deficits in various neuropsychiatric disorders. However, research investigating the role of this system in controlling cortical circuits and computations therein is limited. Here, we review the (1) basic anatomy of cortical circuits, (2) anatomical architecture of the cortical DYN/KOR system, (3) functional regulation of cortical synaptic transmission and microcircuit function by the DYN/KOR system, (4) regulation of behavior by the cortical DYN/KOR system, (5) implications for the DYN/KOR system for human health and disease, and (6) future directions and unanswered questions for the field. Further work elucidating the role of the DYN/KOR system in controlling cortical information processing and associated behaviors will be of importance to increasing our understanding of principles underlying neuropeptide modulation of cortical circuits, mechanisms underlying sensation and perception, motivated and emotional behavior, and cognition. Increased emphasis in this area of study will also aid in the identification of novel ways to target the DYN/KOR system to treat neuropsychiatric disorders.