Homeostatic Synaptic Scaling Establishes the Specificity of an Associative Memory

Accurate memory formation has been hypothesized to depend on both rapid Hebbian plasticity for initial encoding, and slower homeostatic mechanisms that prevent runaway excitation and subsequent loss of memory specificity. Here, we tested the role of synaptic scaling in shaping the specificity of conditioned taste aversion (CTA) memory, a Hebbian plasticity-dependent form of associative learning. We found that CTA memory initially generalized to non-conditioned tastants (generalized aversion), becoming specific to the conditioned tastant only over the course of many hours. Blocking synaptic scaling in the gustatory cortex (GC) prolonged the duration of the initial generalized aversion and enhanced the persistence of synaptic strength increases observed after CTA. Taken together, these findings demonstrate that synaptic scaling is important for sculpting the specificity of an associative memory and suggest that the relative strengths of Hebbian and homeostatic plasticity can modulate the balance between stable memory formation and generalization.