Electrophysiological analysis of paraventricular thalamic neurons co-expressing kappa and mu opioid receptors

The paraventricular thalamus (PVT) is a central node in the integration of stress- and reward-related information that may serve as a pivotal site for opioid receptors to exert their effects. Kappa opioid receptors (KOPrs) and mu opioid receptors (MOPrs) have dissociable and opposing roles in circuits of stress and reward. Interestingly, both are highly expressed in the PVT, however it is not known how aversive KOPr and rewarding MOPr signalling converges to dictate PVT activity and, by proxy, whole brain effects. We have investigated the function of KOPrs and MOPrs in single PVT neurons using whole-cell voltage-clamp recordings in brain slices from female and male mice (4-8 weeks). The majority of PVT neurons (69%) co-expressed KOPr and MOPr. Activation of either receptor produced outward K+ currents, with no age and sex differences. In neurons co-expressing both opioid receptors, the MOPr-induced K+ current reversed around the theoretical equilibrium potential, whilst the KOPr current did not reverse at any holding potential tested. Furthermore, investigation of apparent inward currents produced by MOPr inverse agonists suggested the presence of tonically active MOPrs, predominantly in the anterior PVT. Activation of both KOPrs and MOPrs decreased glutamatergic input to PVT neurons by around 40%, whereas only KOPr activation decreased GABAergic input, by 46%. Together these data suggest that the balance of activation of KOPrs and MOPrs in the PVT plays a critical role in integrating stress- and reward-related signals.