Basolateral amygdala activity is required for enhancement of memory consolidation produced by histone deacetylase inhibition in the hippocampus

Abstract

Histone acetylation, a type of chromatin modification that allows increased gene transcription and can be pharmacologically promoted by histone deacetylase (HDAC) inhibitors (HDACis), has been consistently associated with promoting memory formation in the hippocampus. The basolateral nucleus of the amygdala (BLA) is a brain area crucially involved in enabling hormones and drugs to influence memory formation. Here, we show that BLA activity is required for memory enhancement by intrahippocampal administration of an HDACi. Two different HDACis, sodium butyrate (NaB) and trichostatin A (TSA), differentially enhanced the retention of memory for inhibitory avoidance (IA) when administered to the dorsal hippocampus after training. TSA showed a biphasic pattern of response during consolidation, in which infusions given immediately or 3h after training produced memory enhancement, whereas no effect was observed when it was infused 1.5 or 6h posttraining. Muscimol (MUS)-induced unilateral functional inactivation of the BLA prevented the enhancement of memory retention produced by posttraining infusion of TSA into the ipsilateral hippocampus. TSA did not affect IA extinction or reconsolidation. These results indicate that HDACis can increase IA memory retention when given into the hippocampus, and, most importantly, BLA activity is necessary for enabling HDACi-induced influences on memory formation.

TrkB blockade in the hippocampus after training or retrieval impairs memory: protection from consolidation impairment by histone deacetylase inhibition

“…Animals were implanted under anesthesia with ketamine (75 mg/kg) and xylasine (25 mg/kg) with bilateral 8.0-mm, 23-gauge guide cannulae aimed 1.0 mm above the CA1 area of the dorsal hippocampus as described in previous studies (Blank et al 2014;Roesler et al 2003). Coordinates (anteroposterior, -4.3 mm from bregma; mediolateral, ±3.0 mm from bregma; ventral, -2.0 mm from skull surface) were obtained from the atlas of Paxinos and Watson (2007).…”

“…The general procedures for intrahippocampal infusions were described in previous reports (Blank et al 2014;Jobim et al 2012). At the time of infusion, a 30-gauge infusion needle was fitted into the guide cannula.…”

“…In the second experiment, rats received a bilateral intrahippocampal 1.0-ll infusion of saline or NaB (100 mM dissolved in saline) and immediately after reactivation they were infused with vehicle (1 % DMSO in saline) or ANA-12 (1.0 lg/ll dissolved in vehicle). The doses of NaB and ANA-12 were chosen on the basis of previous studies (Blank et al 2014;Spaeth et al 2012). Drug solutions were freshly prepared before each experiment.…”

“…The general procedures for IA training and retention testing were described in previous reports (Blank et al 2014;Jobim et al 2012;Pedroso et al 2013). The IA apparatus was a 50 9 25 9 25-cm acrylic box (Albarsch, Porto Alegre, Brazil) whose floor consisted of parallel caliber stainless steel bars (1 mm diameter) spaced 1 cm apart.…”

“…Systemic or intracerebral administration of HDAC inhibitors has been used as an approach to produce memory enhancement. NaB and other inhibitors including trichostatin A (TSA), suberoylanilide hydroxamic acid (SAHA), and valproic acid have been shown to enhance LTP and the formation and extinction of memory for fear-motivated tasks (Blank et al 2014;Bredy and Barad 2008;Lattal et al 2007;Levenson et al 2004;Stafford et al 2012;Vecsey et al 2007). We have previously shown that infusions of either NaB or TSA into the dorsal hippocampus given immediately or 3 h after training resulted in a long-lasting enhancement of IA memory (Blank et al 2014), and systemic administration of NaB enhanced memory in aged rats (Blank et al 2015;Reolon et al 2011).…”