Arc/Arg3.1 mediates a critical period for spatial learning and hippocampal networks.

During early postnatal development, sensory regions of the brain undergo periods of heightened plasticity which sculpt neural networks and lay the foundation for adult sensory perception. Such critical periods were also postulated for learning and memory but remain elusive and poorly understood. Here, we present evidence that the activity-regulated and memory-linked gene Arc/Arg3.1 is transiently up-regulated in the hippocampus during the first postnatal month. Conditional removal of Arc/Arg3.1 during this period permanently alters hippocampal oscillations and diminishes spatial learning capacity throughout adulthood. In contrast, post developmental removal of Arc/Arg3.1 leaves learning and network activity patterns intact. Long-term memory storage continues to rely on Arc/Arg3.1 expression throughout life. These results demonstrate that Arc/Arg3.1 mediates a critical period for spatial learning, during which Arc/Arg3.1 fosters maturation of hippocampal network activity necessary for future learning and memory storage.