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Planning and directing thought and behavior require the working memory (WM) functions of prefrontal cortex. WM is compromised by stress, which activates phosphatidylinositol (PI)-mediated IP 3 -PKC intracellular signaling. PKC overactivation impairs WM operations and in vitro studies indicate that IP 3  receptor (IP 3 R)-evoked calcium release results in SK channel-dependent hyperpolarization of prefrontal neurons. However, the effects of IP 3 R signaling on prefrontal function have not been investigated. The present findings demonstrate that blockade of IP 3 R or SK channels in the prefrontal cortex enhances WM performance in rats, suggesting that both arms of the PI cascade influence prefrontal cognitive function.

Blockade of IP3-mediated SK channel signaling in the rat medial prefrontal cortex improves spatial working memory

Blockade of IP₃-mediated SK channel signaling in the rat medial prefrontal cortex improves spatial working memory