The article discusses the interplay between hippocampal long-term potentiation (LTP) and long-term depression (LTD) in enabling memory representations. LTP and LTD are Hebbian forms of synaptic plasticity that are believed to underlie associative learning. Persistent (>24 hours) LTP and LTD exhibit distinct frequency dependencies and molecular profiles in different hippocampal subfields. Causal and genetic studies in behaving rodents indicate that LTP and LTD play complementary roles in the acquisition and retention of spatial memory. LTP is likely responsible for generating a record of spatial experience, which can be reused to expedite subsequent learning. In contrast, LTD enables the modification and dynamic updating of this representation, ensuring that detailed spatial content information is included and the schema remains unique. The dynamic interplay between LTP and LTD supports the generation of complex associative memories that are resistant to generalization. The article also highlights the importance of metaplasticity and slow-onset potentiation (SOP) in modulating synaptic strength, and discusses the causal evidence that LTP and LTD support the acquisition and retention of long-term associative experience. Finally, it explores how the hippocampus is instructed to express either persistent LTP or persistent LTD, considering the roles of various brain regions such as the locus coeruleus (LC) and the ventral tegmental area (VTA).The article discusses the interplay between hippocampal long-term potentiation (LTP) and long-term depression (LTD) in enabling memory representations. LTP and LTD are Hebbian forms of synaptic plasticity that are believed to underlie associative learning. Persistent (>24 hours) LTP and LTD exhibit distinct frequency dependencies and molecular profiles in different hippocampal subfields. Causal and genetic studies in behaving rodents indicate that LTP and LTD play complementary roles in the acquisition and retention of spatial memory. LTP is likely responsible for generating a record of spatial experience, which can be reused to expedite subsequent learning. In contrast, LTD enables the modification and dynamic updating of this representation, ensuring that detailed spatial content information is included and the schema remains unique. The dynamic interplay between LTP and LTD supports the generation of complex associative memories that are resistant to generalization. The article also highlights the importance of metaplasticity and slow-onset potentiation (SOP) in modulating synaptic strength, and discusses the causal evidence that LTP and LTD support the acquisition and retention of long-term associative experience. Finally, it explores how the hippocampus is instructed to express either persistent LTP or persistent LTD, considering the roles of various brain regions such as the locus coeruleus (LC) and the ventral tegmental area (VTA).