title: 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.
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Center for Molecular Structural Biology, Federal University of Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
authors.forename: Martina
authors.initials: M
authors.lastname: Blank
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Arethuza S
authors.initials: AS
authors.lastname: Dornelles
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil.
authors.forename: Aline
authors.initials: A
authors.lastname: Werenicz
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil.
authors.forename: Luciana A
authors.initials: LA
authors.lastname: Velho
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil.
authors.forename: Diana F
authors.initials: DF
authors.lastname: Pinto
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil.
authors.forename: Ana Cláudia
authors.initials: AC
authors.lastname: Fedi
authors.affiliation: National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil; Neurobiology and Developmental Biology Laboratory, Faculty of Biosciences, Pontifical Catholic University, 90619-900 Porto Alegre, RS, Brazil.
authors.forename: Nadja
authors.initials: N
authors.lastname: Schröder
authors.affiliation: Laboratory of Neuropharmacology and Neural Tumor Biology, Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, 90050-170 Porto Alegre, RS, Brazil; Cancer Research Laboratory, University Hospital Research Center (CPE-HCPA), Federal University of Rio Grande do Sul, 90035-003 Porto Alegre, RS, Brazil; National Institute for Translational Medicine, 90035-003 Porto Alegre, RS, Brazil. Electronic address: rafael.roesler@pq.cnpq.br.
authors.forename: Rafael
authors.initials: R
authors.lastname: Roesler
mesh_terms: D000818:Animals; D066272:Basolateral Nuclear Complex / Q000502:physiology*; D020148:Butyric Acid / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D008568:Memory / Q000187:drug effects*; D017208:Rats, Wistar
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D020148:Butyric Acid; C012589:trichostatin A
keywords: Amygdala; Chromatin; Epigenetics; Hippocampus; Histone deacetylase; Memory consolidation