Synapse Innervation and Associative Memory Cell Are Recruited for Integrative Storage of Whisker and Odor Signals in the Barrel Cortex through miRNA-Mediated Processes.

Zhuofan Lei,Zhenhua Song,Na Chen,Ke Ma,Shan Cui,Jin-Hui Wang,Dangui Wang,Wei Lu

doi:10.3389/fncel.2017.00316

Abstract

Associative learning is a common way for information acquisition, and the integrative storage of multiple associated signals is essential for associative thinking and logical reasoning. In terms of the cellular mechanism for associative memory, our studies by behavioral task and cellular imaging demonstrate that paired whisker and odor stimulations lead to odorant-induced whisker motion and associative memory cell recruitment in the barrel cortex (BC), which is driven presumably by synapse innervation from co-activated sensory cortices. To confirm these associative memory cells and synapse innervations essential for associative memory and to examine their potential mechanisms, we studied a causal relationship between epigenetic process and memory cell/synapse recruitment by manipulating miRNAs and observing the changes from the recruitments of associative memory cells and synapse innervations to associative memory. Anti-miRNA-324 and anti-miRNA-133a in the BC significantly downregulate new synapse innervation, associative memory cell recruitment and odorant-induced whisker motion, where Tau-tubulin kinase-1 expression is increased. Therefore, the upregulated miRNA-324 in associative learning knocks down Ttbk1-mediated Tau phosphorylation and microtubule depolymerization, which drives the balance between polymerization and depolymerization toward the axon prolongation and spine stabilization to initiate new synapse innervations and to recruit associative memory cells.

Highlights

Associative memory plays important roles in cognitive processes, such as logical reasoning and associative thinking (Kandel and Pittenger, 1999; Bailey et al, 2015; Wang and Cui, 2017)
We have reported the functional connection from the piriform cortex (PC) to the barrel cortex (BC) in conditioned reflexes (CR)-formation mice (Wang et al, 2015), it is noteworthy that these synaptic contacts are examined by seeing their functions in spines/boutons and their labeling with synapsemarker proteins
We aim to study the causal relationship from new synapse innervations and associative memory cell recruitment to associative memory as well as to examine their molecular mechanisms by manipulating epigenetic process

Summary

Introduction

Associative memory plays important roles in cognitive processes, such as logical reasoning and associative thinking (Kandel and Pittenger, 1999; Bailey et al, 2015; Wang and Cui, 2017). Since the balance between microtubule polymerization and depolymerization influences tubulin growth that plays a critical role in axon prolongation and spine stabilization (Dent and Kalil, 2001; Mitsuyama et al, 2009; Wilson et al, 2012; Ueda et al, 2015), we hypothesize that associative learning induces a chain reaction of miRNA expression change, microtubule polymerization, axon prolongation and synapse innervation for associative memory cell recruitment. We aim to examine how miRNA-324/miRNA-133a and their regulated molecules serve to the recruitments of new synapse innervations and associative memory cells for the integration and storage of associated signals

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Conclusion