The Mechanisms Underlying Associative Learning And Memory Cell Formation For Multiple Signals

Background:Associative learning is a common way for information acquisition,and associative memory is essential for the cognitive processes related to logical reasoning,associative thinking and comparisons.Associations of two sensory signals in classical conditioning or sensory signal plus operation in operant conditioning lead to their associated retrievals.In terms of the cellular mechanisms,activity-dependent plasticity arises in the synapses and neurons after associative learning.Memory cells that encode these two associated signals are detected in the co-activated sensory cortices and their downstream brain areas.The recruitment of associative memory cells for two signals is presumably driven by mutual synapse innervations between sensory cortical neurons.Except for two associated signals,it remains to be tested whether associative memory cells to encode multiple sensory signals can be recruited.The storage of the multiple signals in individual neurons may expand memory volume,strengthen cognition ability and facilitate creative inspirations.We aim to study whether new synapse innervations recruit associative memory cells to store triple signals.Methods:In terms of strategies to address this issue,the associations of triple sensory signals were performed by pairing whisker,olfaction and tail signals in the mice.After odorant-induced and tail-induced whisker motions alongside whisker-induced whisker motion emerge,cell electrophysiology and imaging in vivo were applied to detect barrel cortical neurons that encode these triple signals as well as neural tracing was used to detect synapse innervations from the piriform and S1-tail cortices to the barrel cortical neurons.microRNA antagomirs were injected into the barrel cortices of the mice that would receive the pairing of triple signals to examine the involvement of epigenetic processes in associative memory.If synapse innervation and meory cell recruitments are required,the downregulations of axon projection and synapse formation by anti-miRNAs would remove associative memory.Results:Paired whisher,odor and tail stimulations lead to odorant-induced and tail-induced whisher motions alongside whisker-induced whisker mition.Nerve cells in the barrel cortex process whisker,odor and tail signals after this association.Barrel cortical neurons receive more synapse innervations from the axons of piriform and S1-tail cortical neurons in CR-formation mice.GABAergic and glutamatergic neurons and synapses undergo plastic changes in their functions and mutual innervation.miRNA-324-5p and miRNA-133a-3p are required for synapse innervation and associative memory.Conclusions:The co-activations of sensory cortices trigger their mutual synapse innervations that recruit memory cells to store multiple associated signals,which require miRNA-324 and miRNA-133a.