Inhibitory plasticity supports replay generalization in the hippocampus

Memory consolidation assimilates recent experiences into long-term memory.
This process requires the replay of learned sequences, though the content
of these sequences remains controversial. Recent work has shown that the
statistics of replay deviate from those of experience: stimuli that are
experientially salient may be either recruited or suppressed from
sharp-wave ripples. We find that this phenomenon can be explained
parsimoniously and biologically plausibly by a Hebbian spike
time-dependent plasticity rule at inhibitory synapses. Using models at
three levels of abstraction--leaky integrate-and-fire, biophysically
detailed, and abstract binary-we show that this rule enables efficient
generalization. We make specific predictions about the consequences of
intact and perturbed inhibitory dynamics for network dynamics and
cognition. Finally, we use optogenetics to artificially implant
nongeneralizable representations into the network, and find that these
representations also accumulate inhibition during sharp-wave ripples,
experimentally validating a major prediction of our model. Our work
outlines a potential direct link between the synaptic and cognitive levels
of memory consolidation, with implications for both normal learning and
neurological disease.