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

• Published in: Journal of Neural Transmission Vol. 123; no. 3; pp. 159 - 165
• Main Authors: Blank, Martina, Petry, Fernanda S., Lichtenfels, Martina, Valiati, Fernanda E., Dornelles, Arethuza S., Roesler, Rafael
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01-03-2016
• Subjects: Animals; Brain-Derived Neurotrophic Factor - metabolism; Hippocampus - physiology; Histone Deacetylase Inhibitors - pharmacology; Histone Deacetylases - metabolism; Male; Medicine; Medicine & Public Health; Memory Consolidation - drug effects; Memory Consolidation - physiology; Neurology; Neurosciences; Psychiatry; Rats; Rats, Wistar; Receptor, trkB - metabolism; Signal Transduction - physiology; Translational Neurosciences - Original Article; Memory consolidation; Inhibitory avoidance; Histone deacetylase; Reconsolidation; TrkB; Hippocampus
• ISSN: 0300-9564; 1435-1463
• DOI: 10.1007/s00702-015-1464-7

Relatively little is known about the requirement of signaling initiated by brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), in the early phases of memory consolidation, as well as about its possible functional interactions with epigenetic mechanisms. Here we show that blocking TrkB in the dorsal hippocampus after learning or retrieval impairs retention of memory for inhibitory avoidance (IA). More importantly, the impairing effect of TrkB antagonism on consolidation was completely prevented by the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB). Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or NaB before training, followed by an infusion of either vehicle (VEH) or the selective TrkB antagonist ANA-12 immediately after training. In a second experiment, the infusions were administered before and after retrieval. ANA-12 after either training or retrieval produced a significant impairment in a subsequent memory retention test. Pretraining administration of NaB prevented the effect of ANA-12, although NaB given before retrieval did not alter the impairment resulting from TrkB blockade. The results indicate that inhibition of BDNF/TrkB in the hippocampus can hinder consolidation and reconsolidation of IA memory. However, TrkB activity is not required for consolidation in the presence of NaB, suggesting that a dysfunction in BDNF/TrkB signaling can be fully compensated by HDAC inhibition to allow hippocampal memory formation.