Cell-type-specific synaptic scaling mechanisms differentially contribute to associative learning

Excitatory synaptic scaling regulates network dynamics by proportionally adjusting excitatory synaptic strengths after sensory perturbations. During associative learning, blocking excitatory scaling in conditioned taste aversion paradigms prolongs generalized aversive responses and delays memory specificity. Recent evidence also implicates inhibitory synaptic scaling in the regulation of network dynamics. Specifically, parvalbumin (PV)-expressing inhibitory neurons, targeting perisomatic regions of excitatory (E) pyramidal neurons, and somatostatin (SST)-expressing neurons, targeting distal dendrites, exhibit distinct scaling responses. This leaves open the question of how complex plasticity mechanisms regulate recurrent excitatory-inhibitory circuit dynamics in associative learning. Using computational approaches, we demonstrate that Hebbian plasticity drives memory generalization to novel stimuli not presented during conditioning. Following conditioning, diverse synaptic scaling mechanisms progressively induce memory specificity, which can be regulated by top-down inputs. Our results reveal that, in the absence of excitatory scaling, PV-to-E scaling can effectively compensate and rescue memory specificity, highlighting the presence of degenerate mechanisms in the brain. Notably, in the process of establishing memory specificity, excitatory scaling and PV-to-E scaling function synergistically, while concurrently opposing SST-to-E scaling. The synergistic and antagonistic plasticity mechanisms are orchestrated to shape the temporal evolution of memory representations, from generalized to precise.