Working memory training triggers delayed chromatin remodeling in the mouse corticostriatothalamic circuit

CASSANELLI M; CLADOUCHOS ML; FERNÁNDEZ MACEDO G; SIFONIOS L; GIACCARDI L; GUTIÉRREZ ML; GRAVIELLE, M. C.; WIKINSKI S.

PROGRESS OF NEUROPSYCHOPHARMACOLOGY AND BIOLOGICAL PSYCHIATRY

PERGAMON-ELSEVIER SCIENCE LTD

Lugar: Amsterdam; Año: 2015 p. 93 - 103

0278-5846

Working memory is a cognitive function serving goal-oriented behavior. Lesion and electrophysiological studies recognized the integrity of the corticostriatothalamic circuitry as key for this function to exist. Synaptic plasticity required for this integrity has been recently associated with epigenetic mechanisms. Indeed, in previous works, experimental manipulations of histone modifications had an impact on the performance of this cognitive function. However, whether working memory performance triggers epigenetic changes remains unknown. In this study we explore the consequences of the performance of a working memory task on histone H3 acetylation (AcH3) and histone H3 dimethylation on lysine 27 (H3K27Me2) in the brain regions of the corticostriatothalamic circuit (prelimbic/infralimbic cortex (PrL/IL), dorsomedial striatum (DMSt) and dorsomedial thalamus (DMTh)). For this purpose we first determined the involvement of these areas in the working memory performance by measuring the marker of neuronal activation c-fos in three experimental groups: mice that had performed a spontaneous alternation task in a T-maze (WM), mice in which the choice between the arms of the T-maze was forced by the experimenter (active control) and cage animals. We observed increased c-fos levels in PrL/IL and DMSt in WM group. These animals also presented lower striatal immunoreactivity for AcH3 24 h but not 90 min after the task, compared with cage animals but not with active controls. Increases in H3K27M2, a repressive chromatin mark, were found in the DMSt and DMTh 24 h after the task compared with both controls. All together, these observations are the first indicating delayed chromatin remodeling towards repression after a working memory task.