Blockade of Histone Deacetylation in the Brain Modulates the Expression of Transcription Factors c-FOS and ZENK and Potentiates the Formation of Long-Term Memory in Neonatal Chicks

Abstract

The aim of the present work was to study the role of histone acetylation in brain cells in the formation of memory in neonatal chicks by investigating the effects of intracerebral administration of the histone deacetylase inhibitor trichostatin A on the formation of memory in “weak” learning by chicks of a passive avoidance task and on the expression of transcription factors c-Fos and ZENK. Administration of trichostatin A before training led to a significant dose-dependent increase in memory on testing at 24 h. In addition, trichostatin A induced c-Fos and ZENK expression in a number of brain structures: the intermediate medial mesopallium and the hippocampus showed increases in the density of cells expressing ZENK and the intermediate arcopallium and dorsocaudal nidopallium showed increases in cells expressing c-Fos. Subsequent learning did not produce additional expression of these genes in any of these structures. These results demonstrate the possibility of increasing “weak” memory in chicks using a histone deacetylase inhibitor, supporting the hypothesis that histone acetylation has a role in the consolidation of long-term memory. This effect may be linked with activation of the expression of transcription factor genes in brain structures involved in memory consolidation in this model.