A widely accepted hypothesis suggests that changes in synaptic strength underlie the formation of memories in the brain. LTP is a mechanism of synaptic strengthening. Induction of LTP depends on NMDA receptor activation, and its expression depends in part on protein kinase activity. Studies of knock-out mice suggest that LTP is critical for hippocampus-based memory. Genetic studies in Drosophila implicate cAMP metabolism in classical conditioning, a form of unconscious memory. Consolidating memories for long-term retention depends on the cAMP-inducible transcription factor CREB.