Neuronal plasticity occurs in associative memory. Associative memory cells are recruited for the integration and storage of associated signals. The coordinated refinements and interactions of associative memory cells including glutamatergic and GABAergic neurons remain elusive, which we have examined in a mouse model of associative learning. Paired olfaction, tail and whisker stimulations lead to odorant-induced and tail-induced whisker motions alongside whisker-induced whisker motion. In mice that show this cross-modal associative memory, barrel cortical glutamatergic and GABAergic neurons are recruited to encode the newly learned odor and tail signals alongside the innate whisker signal. These glutamatergic neurons are functionally upregulated, and GABAergic neurons are refined in a homeostatic manner. The mutual innervations between these glutamatergic and GABAergic neurons are upregulated. Therefore, the co-activations of sensory cortices by pairing the input signals recruit their glutamatergic and GABAergic neurons to be associative memory cells, which undergo coordinated refinement among glutamatergic and GABAergic neurons as well as homeostatic plasticity among subcellular compartments in order to drive these cells toward the optimal state for the integrative storage of associated signals.
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