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Activation of κ opioid receptors increases intrinsic excitability of dentate gyrus granule cells

Non‐technical summary  The hippocampus is an area of the brain that is important for learning and memory and a locus for hyperexcitable activity, such as epilepsy. The dentate gyrus (DG) of the hippocampus controls information flow into the rest of the hippocampus, and thus provides protection from excess activity. Under pathological conditions, such as epilepsy, this protective feature is circumvented and uninhibited activity flows throughout the hippocampus. Activation of kappa (κ) opioid receptors (KORs) prevents both the behavioural and electroencephalographic measures of seizures in several models of epilepsy, and other complex behaviours such as stress‐induced deficits in learning. Understanding the cellular effect of KOR activation is critical to our understanding of DG function. In this study we show that, contrary to our hypothesis, activation of the KORs increases excitability of the DG cells. These results suggest that regulation of activity in the DG by activation of KORs is more complex than previously thought.