Preventing cognitive impairment in mouse genetic models of Down syndrome by early postnatal suppression of Kir3.2 channel signaling

(3 sentence limit) In mouse genetic models of Down syndrome (DS), enhanced inhibitory efficiency limits hippocampal synaptic plasticity thus negatively affecting cognition. Here we hypothesized that these changes occur during early postnatal periods as a compensatory reaction to excessive neuronal hyperpolarization, caused by increased signaling through Kir3.2 channels, preventing neonatal neurons from “seeing” each other during the formation of nascent neural circuits. While testing this hypothesis, we will examine the therapeutic potential of antagonists of the GABAB receptors as cognitive enhancers in DS.