Abstract

Visual imprinting is a learning process whereby young animals come to prefer a visual stimulus after exposure to it (training). The intermediate medial mesopallium (IMM) in the domestic chick forebrain is critical for visual imprinting and contributes to molecular regulation of memory formation. We investigated the role of micro-RNAs (miRNAs) in such regulation. Twenty-four hours after training, miRNA spectra in the left IMM were compared between chicks with high preference scores (strong memory for imprinting stimulus), and chicks with low preference scores (weak memory for imprinting stimulus). Using criteria of significance and expression level, we chose gga-miR-130b-3p for further study and found that down-regulation correlated with learning strength. No effect was detected in posterior nidopallium, a region not involved in imprinting. We studied two targets of gga-miR-130b-3p, cytoplasmic polyadenylation element binding proteins 1 (CPEB-1) and 3 (CPEB-3), in two subcellular fractions (P2 membrane-mitochondrial and cytoplasmic) of IMM and posterior nidopallium. Only in the left IMM was a learning-related effect observed, in membrane CPEB-3. Variances from the regression with preference score and untrained chicks suggest that, in the IMM, gga-miR-130b-3p level reflects a predisposition, i.e. capacity to learn, whereas P2 membrane-mitochondrial CPEB-3 is up-regulated in a learning-specific way.

Highlights

  • Successful study of the molecular mechanisms of learning and memory requires that learning-related neural changes and learning-related behaviour are readily measurable

  • No learning-related effects were found in the posterior pole of the nidopallium (PPN); tables summarising results from this region have been placed in Supplementary Tables S2–S4 in Supplementary Material

  • Taken together with the significant correlation between preference score and M-cytoplasmic polyadenylation element binding protein 3 (CPEB-3) in the left intermediate medial mesopallium (IMM) and the values of the intercepts at preference scores 50 and 100, these results suggest that the correlation in the left IMM arose as a result of training and as a function of the strength of learning

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Summary

Introduction

Successful study of the molecular mechanisms of learning and memory requires that learning-related neural changes and learning-related behaviour are readily measurable. According to these criteria, learning-related molecular changes have been found to occur in the IMM after imprinting in a progression from transient/labile to trophic modifications, culminating in stable recognition memory[14,15] These molecular changes include up-regulation of several proteins implicated in neurotransmitter release (clathrin, dynamin-1 and amyloid precursor protein), cellular adhesion (neural cell adhesion proteins and cognin), mitochondrial dynamics (mitofusin-1 and dynamin-related protein-1) and mitochondrial energy metabolism (subunits I and II of cytochrome c oxidase)[16,17,18,19,20,21,22,23,24]. Cytoplasmic polyadenylation element binding protein 3 (CPEB-3) in a membrane/mitochondrial fraction, showed learning-related up-regulation lateralized to the left IMM

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