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Anterior thalamic lesions produce chronic and profuse transcriptional deregulation in retrosplenial cortex: a model of retrosplenial hypoactivity and covert pathology

Published online by Cambridge University Press:  11 March 2008

G.L. Poirier*
Affiliation:
School of Psychology, Cardiff University, Cardiff, UK
K.L. Shires*
Affiliation:
School of Psychology, Cardiff University, Cardiff, UK School of Biosciences, Cardiff University, Cardiff, UK Division of Reproduction and Endocrinology, School of Biomedical and Health Sciences, King's College, London, UK
D. Sugden
Affiliation:
Division of Reproduction and Endocrinology, School of Biomedical and Health Sciences, King's College, London, UK
E. Amin
Affiliation:
School of Psychology, Cardiff University, Cardiff, UK
K.L. Thomas
Affiliation:
School of Biosciences, Cardiff University, Cardiff, UK
D.A. Carter
Affiliation:
School of Biosciences, Cardiff University, Cardiff, UK
J.P. Aggleton
Affiliation:
School of Psychology, Cardiff University, Cardiff, UK
*
Correspondence should be addressed to: Guillaume Poirier, School of Psychology, Cardiff University, 70 Park Place, Cardiff, UK, CF10 3AT tel: 44 (0) 29 2087 5301 fax: 44 (0) 29 2087 4858 email: [email protected]
Kate Shires, Centre for Cognitive and Neural Systems, Dept of Neuroscience, University of Edinburgh, 1 George Square, Edinburgh, UK, EH8 9JZ tel: +44 131 650 4571 fax: +44 131 651 1835 email: [email protected]

Abstract

Anterior thalamic lesions are thought to produce ‘covert pathology’ in retrosplenial cortex, but the causes are unknown. Using microarray analyses we tested the hypothesis that thalamic damage causes a chronic, hypofunction of metabolic and plasticity-related pathways (Experiment 1). Rats with unilateral, anterior thalamic lesions were exposed to a novel environment for 20 min, and granular retrosplenial tissue sampled from both hemispheres 30 min, 2 hours and 8 hours later. Complementary statistical approaches (analyses of variance, predictive patterning and gene set-enrichment analysis) revealed pervasive gene expression differences between retrosplenial cortex ipsilateral to the thalamic lesion and contralateral to the lesion. Selected gene differences were validated by QPCR, immunohistochemistry (Experiment 1) and in situ hybridization (Experiment 2). Following thalamic lesions, the retrosplenial cortex undergoes profuse cellular transcriptome changes including lower relative levels of specific mRNAs that are involved in energy metabolism and neuronal plasticity. These changes in functional gene expression might be driven largely by decreases in the expression of genes encoding transcription factors including brd8, c-fos, fra-2, klf5, nfix, nr4a1, smad3, smarcc2 and zfp9, with far fewer (nfat5, neuroD1 and RXRγ) showing increases. These findings have implications for conditions such as diencephalic amnesia and Alzheimer's disease in which both anterior thalamic pathology and retrosplenial cortex hypometabolism are prominent.

Type
Original Articles
Copyright
Copyright © Cambridge University Press 2008

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References

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