Regulation of HDAC1 and HDAC2 during consolidation and extinction of fear memory.

ABSTRACT

Histone deacetylases (HDACs) regulate gene expression epigenetically through synchronized removal of acetyl groups from histones required towards memory consolidation. Moreover, dysregulated epigenetic machinery during fear or extinction learning may result in altered expression of some of these genes and result in Post Traumatic Stress Disorder (PTSD). In the present study, region-specific expression of Histone deacetylase 1 (HDAC1) and Histone deacetylase 2 (HDAC2) was correlated to the acetylation of histones H3 and H4 and the resultant conditioned response, in rats undergone fear and extinction learning. The neuronal activation, histone acetylation at H3/H4 and expression of HDAC1/HDAC2 in centrolateral amygdala (CeL) and centromedial amygdala (CeM) of central Amygdala (CeA) and prelimbic (PL) and infralimbic (IL) of Prefrontal cortex (PFC) were found to be associated in a differential manner following fear and extinction learning. Moreover in CeM, the main output of the fear circuitry, the level of HDAC1 was down-regulated following conditioning and up-regulated following extinction as opposed to which HDAC2 was down-regulated in CeM following conditioning but not following extinction. Furthermore, in CeL the HDAC1 was upregulated and HDAC2 was downregulated following conditioning and extinction. This has important implications in speculating of the role of HDACs in fear memory consolidation and its extinction.