Although most words have more than one meaning, the mechanisms underlying new-meaning learning have been understudied. This one-to-many mapping poses even greater challenges for second language learners. The present study examined the behavioral mechanisms underlying new-meaning learning among non-native speakers by focusing on the effects of word familiarity, an approximate measure of lexical quality. We found that learning new meanings for more familiar L2 words was easier, as indicated by better recognition and cued-recall performance throughout the learning phase and in delayed tests. Furthermore, new-meaning learning facilitated, rather than impeded, the processing of original meanings, especially after a delay. Comparing these findings with those from previous studies involving native speakers, it appears that lexical quality influences how new and prior knowledge interact during new-meaning learning.

Sleep interacts reciprocally with immune system activity, but its specific relationship with microglia-the resident immune cells in the brain-remains poorly understood. Here, we show in mice that microglia can regulate sleep through a mechanism involving Gi-coupled GPCRs, intracellular Ca2+ signaling and suppression of norepinephrine transmission. Chemogenetic activation of microglia Gi signaling strongly promoted sleep, whereas pharmacological blockade of Gi-coupled P2Y12 receptors decreased sleep. Two-photon imaging in the cortex showed that P2Y12-Gi activation elevated microglia intracellular Ca2+, and blockade of this Ca2+ elevation largely abolished the Gi-induced sleep increase. Microglia Ca2+ level also increased at natural wake-to-sleep transitions, caused partly by reduced norepinephrine levels. Furthermore, imaging of norepinephrine with its biosensor in the cortex showed that microglia P2Y12-Gi activation significantly reduced norepinephrine levels, partly by increasing the adenosine concentration. These findings indicate that microglia can regulate sleep through reciprocal interactions with norepinephrine transmission.