CONICET | Buscador de Institutos y Recursos Humanos

A working memory task induces repressive epigenetic changes in dorsomedial striatum of mice.Working memory requires the integrity of frontostriatothalamic circuitry. Since epigenetic mechanisms are thought to participate in memory processes, this work aims to study the post-translational modifications of histone H3 associated with the performance of a working memory task by C57BL/6 mice. Animals performed a spontaneous alternation task in a T-maze and were sacrificed 24 hours after (n = 9). Control animals were kept in their cages (n = 5). To check the neuronal activation in the structures of the circuit, immunohistochemistry assays for c-Fos were carried out in brain sections containing prelimbic/infralimbic cortex (Cx), dorsomedial striatum (DMS) or dorsomedial thalamic nucleus (DMT) of animals sacrificed 90 minutes after the task. Taking into account the results of this experiment, an immunohistochemistry assay for dimethylated (Lys27) or acetylated (Lys9,14) H3, considered to have a repressive or activating effect on transcription respectively was performed in sections containing Cx or DMS. Animals had a percent spontaneous alternation statistically greater than chance level ((66 ± 12)% vs. 50 %, p<0.005). Immunohistochemistry assays for c-Fos confirmed the activation of the frontostriatothalamic circuit in response to the working memory task. C-Fos positive cells were found to be increased in Cx (372% vs. controls, p<0.005) and DMS (49% vs. controls, p<0.05). Undetectable levels were seen in DMT. In dorsolateral striatum (DLS), which was used as a control structure, c-Fos positive cells were found to be unchanged. No changes were observed in the levels of dimethylated or acetylated H3 in Cx. However, dimethylated H3 was found to be increased in the DMS (35% vs. control, p<0.05) of mice subjected to the behavioral test. In addition, acetylated H3 levels were lower in these animals? DMS (33% vs. control, p<0.05). No changes were observed in the DLS for either H3 modification. C-Fos activation in the prefrontal cortex is in accordance with evidence indicating its role in working memory. However, this structure?s activation seems not to leave marks on chromatin that could modulate its functioning after the task. On the contrary, the dorsomedial striatum shows both c-Fos activation and changes in histone H3 post-translational modification levels. These changes could represent some sort of memory trace associated with a relatively long-lasting response to previous experience.