title: Anterior thalamic lesions produce chronic and profuse transcriptional de-regulation in retrosplenial cortex: A model of retrosplenial hypoactivity and covert pathology.
abstract: Anterior thalamic lesions are thought to produce 'covert pathology' in retrosplenial cortex, but the causes are unknown. Microarray analyses tested the hypothesis that thalamic damage causes a chronic, hypo-function of metabolic and plasticity-related pathways (Experiment 1). Rats with unilateral, anterior thalamic lesions were exposed to a novel environment for 20 minutes, and granular retrosplenial tissue sampled from both hemispheres 30 minutes, 2h, or 8h 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 hybridisation (Experiment 2). Following thalamic lesions, the retrosplenial cortex undergoes profuse cellular transcriptome changes including lower relative levels of specific mRNAs involved in energy metabolism and neuronal plasticity. These changes in functional gene expression may be largely driven by decreases in the expression of multiple transcription factors, including brd8, c-fos, fra-2, klf5, nfix, nr4a1, smad3, smarcc2, and zfp9, with a much smaller number (nfat5, neuroD1, RXRγ) showing increases. These findings have implications for conditions such as diencephalic amnesia and Alzheimer's disease, where both anterior thalamic pathology and retrosplenial cortex hypometabolism are prominent.
authors.affiliation: School of Psychology, Cardiff University, Wales, UK.
authors.forename: G L
authors.initials: GL
authors.lastname: Poirier
authors.forename: K L
authors.initials: KL
authors.lastname: Shires
authors.forename: D
authors.initials: D
authors.lastname: Sugden
authors.forename: E
authors.initials: E
authors.lastname: Amin
authors.forename: K L
authors.initials: KL
authors.lastname: Thomas
authors.forename: D A
authors.initials: DA
authors.lastname: Carter
authors.forename: J P
authors.initials: JP
authors.lastname: Aggleton