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Recognition memory-induced gene expression in the perirhinal cortex: a transcriptomics analysis.

ABSTRACT: It is possible to identify the key genes and pathways involved in specific physiological processes using transcriptome analyses. However, these powerful new deep sequencing-based methods have rarely been applied to studies of memory function. We used the bow-tie maze to train rats by exposing them to highly familiar objects or to novel objects. Total RNA sequencing was then used to compare the transcriptome of the perirhinal cortices of naïve control rats and rats exposed to novel and familiar stimuli. Differentially expressed genes were identified between group Novel and group Familiar rats and these included genes coding for transcription factors and extracellular matrix-related proteins. Moreover, differences in alternative splicing were also detected between the two groups. To conclude, this study shows that RNA sequencing can be used as a tool to identify differences in gene expression in behaving animals undergoing the same task but encountering different exposures.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE84242 | GEO | 2017/04/05

SECONDARY ACCESSION(S): PRJNA328458

REPOSITORIES: GEO

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Project description:Although immediate early genes (IEGs) such as Bdnf, Arc and Egr1, have been implicated in plasticity, the larger pathways related to memory and memory disorders are not well understood. Here, we combined statistical Affymetrix microarray and behavioral analyses to identify key genes and pathways associated with aging-related cognitive impairment. Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups, based on their Morris water maze performance relative to young-adult (Y) animals. Hippocampal gene expression was assessed in Y, AU and AI on the fifth (last) day of maze training or 21 days posttraining, and in non-trained aged and young animals (eight groups, overall n = 78, one chip/animal). ANOVA, linear contrasts, and overrepresentation analyses identified genes and pathways that differed from Y generally with aging (in both AU and AI) or selectively with cognitive status (only in AI or AU). Plasticity pathways, including insulin/cAMP/IEG signaling, and glycogenolytic and lipogenic pathways, were selectively downregulated (5 days) in AI, whereas Notch2 (regulating oligodendrocyte differentiation) and myelination pathways were upregulated (particularly at 21 days). Downregulation with general aging occurred in signal transduction and axonal growth/transport pathways, whereas upegulation occurred in immune/inflammatory, lipid metabolism/transport (e.g., Lxr-Srebf1), and lysosomal pathways. In AU, receptor/signal transduction genes were selectively upregulated, suggesting possible compensatory mechanisms. Immunohistochemistry confirmed and extended results to the protein level. Thus, this study identified novel cognition-linked processes, suggesting a new model in which energy-intensive, plasticity/lipogenic processes and energy-generating pathways necessary for learning are coordinately downregulated during training, while myelinogenic programs that impair cognition are concurrently activated. Experiment Overall Design: Aged rats were separated into cognitively unimpaired (AU) or impaired (AI) groups, based on their Morris water maze performance relative to young-adult (Y) animals (NT, 5D, and 21D, N=10/group). Hippocampal gene expression was assessed in Y, AU and AI on the fifth (last) day of maze training or 21 days posttraining, and in non-trained aged and young animals (eight groups, overall n = 78, one chip/animal)

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Recognition memory-induced gene expression in the perirhinal cortex: a transcriptomics analysis.

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