title: DNA methyltransferase activity is required for memory-related neural plasticity in the lateral amygdala.
abstract: We have previously shown that auditory Pavlovian fear conditioning is associated with an increase in DNA methyltransferase (DNMT) expression in the lateral amygdala (LA) and that intra-LA infusion or bath application of an inhibitor of DNMT activity impairs the consolidation of an auditory fear memory and long-term potentiation (LTP) at thalamic and cortical inputs to the LA, in vitro. In the present study, we use awake behaving neurophysiological techniques to examine the role of DNMT activity in memory-related neurophysiological changes accompanying fear memory consolidation and reconsolidation in the LA, in vivo. We show that auditory fear conditioning results in a training-related enhancement in the amplitude of short-latency auditory-evoked field potentials (AEFPs) in the LA. Intra-LA infusion of a DNMT inhibitor impairs both fear memory consolidation and, in parallel, the consolidation of training-related neural plasticity in the LA; that is, short-term memory (STM) and short-term training-related increases in AEFP amplitude in the LA are intact, while long-term memory (LTM) and long-term retention of training-related increases in AEFP amplitudes are impaired. In separate experiments, we show that intra-LA infusion of a DNMT inhibitor following retrieval of an auditory fear memory has no effect on post-retrieval STM or short-term retention of training-related changes in AEFP amplitude in the LA, but significantly impairs both post-retrieval LTM and long-term retention of AEFP amplitude changes in the LA. These findings are the first to demonstrate the necessity of DNMT activity in the consolidation and reconsolidation of memory-associated neural plasticity, in vivo.
authors.affiliation: Department of Psychology, Yale University, New Haven, CT, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Maddox
authors.affiliation: Department of Psychology, Yale University, New Haven, CT, USA.
authors.forename: Casey S
authors.initials: CS
authors.lastname: Watts
authors.affiliation: Department of Psychology, Hunter College, The City University of New York, New York, NY, USA; Center for Study of Gene Structure & Function, Hunter College, The City University of New York, New York, NY, USA. Electronic address: glenn.schafe@hunter.cuny.edu.
authors.forename: Glenn E
authors.initials: GE
authors.lastname: Schafe
mesh_terms: D000161:Acoustic Stimulation; D000679:Amygdala / Q000201:enzymology* / Q000502:physiology*; D000818:Animals; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000077209:Decitabine; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005239:Fear / Q000502:physiology; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D011939:Mental Recall / Q000187:drug effects / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D010797:Phthalimides / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014364:Tryptophan / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D010797:Phthalimides; C503639:RG108; D000077209:Decitabine; D014364:Tryptophan; D015254:DNA Modification Methylases; D001374:Azacitidine
keywords: DNA methytransferase; Epigenetics; Fear conditioning; Neural plasticity; Reconsolidation