Coactivations of barrel and piriform cortices induce their mutual synapse innervations and recruit associative memory cells.

After associative learning, a signal induces the recall of its associated signal, or the other way around. This reciprocal retrieval of associated signals is essential for associative thinking and logical reasoning. For the cellular mechanism underlying this associative memory, we hypothesized that the formation of synapse innervations among coactivated sensory cortices and the recruitment of associative memory cells were involved in the integrative storage and reciprocal retrieval of associated signals. Our study indicated that the paired whisker and olfaction stimulations led to an odorant-induced whisker motion and a whisker-induced olfaction response, a reciprocal form of associative memory retrieval. In mice that showed the reciprocal retrieval of associated signals, their barrel and piriform cortical neurons became mutually innervated through their axon projection and new synapse formation. These piriform and barrel cortical neurons gained the ability to encode both whisker and olfaction signals based on synapse innervations from the innate input and the newly formed input. Therefore, the associated activation of sensory cortices by pairing input signals initiates their mutual synapse innervations, and the neurons innervated by new and innate synapses are recruited to be associative memory cells that encode these associated signals. Mutual synapse innervations among sensory cortices to recruit associative memory cells may compose the primary foundation for the integrative storage and reciprocal retrieval of associated signals. Our study also reveals that new synapses onto the neurons enable these neurons to encode memories to new specific signals.