While cognitive processing and memory consolidation occur during both sleep and wake, each sleep state serves an individual and unique role in these processes. Rapid-eye movement (REM) sleep, for instance, is critical for associative learning, in which two unrelated stimuli become cognitively linked. The neurotransmitter norepinephrine (NE) is released throughout wakefulness but is especially abundant during learning and stress. Indeed, NE is believed to play a major role in traditional Hebbian plasticity during memory consolidation, which is guided by the process of long-term potentiation (LTP) where individual synaptic connections between associated neurons strengthen with repeated firing. LTP in the hippocampus is physiologically responsible for associative learning and memory. When presented with new information during reversal learning, reconfiguring memories requires the opposite of LTP, depotentiation (LTD), in order to weaken existing synaptic connections and integrate this new information into learning schema. The presence of NE promotes synaptic strengthening, so LC silence during REM provides a unique neurochemical environment that allows for LTD in normally functioning organisms. However, different neurological or psychiatric pathologies result in aberrant LC activity during REM sleep, resulting in maladaptive changes to the processes of learning, memory, and forgetting.