Arc is critical as a ubiquitous signaling factor in early embryonic development and is required for growth and patterning during gastrulation. The first knockouts (KOs) for Arc were therefore incompatible with life. Subsequent efforts produced homozygous knockout mice by targeting the entire Arc gene rather than portions of the coding region, eliminating dominant negative effects. These animals proved viable and exhibit no gross malformations in neuronal architecture, but express higher levels of the GluR1 subunit and increased miniature excitatory postsynaptic currents (mEPSCs) in addition to displaying deficiencies in long-term memory.