Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala.
Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity i...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3098856?pdf=render |
| _version_ | 1818399417608175616 |
|---|---|
| author | Melissa S Monsey Kristie T Ota Irene F Akingbade Ellie S Hong Glenn E Schafe |
| author_facet | Melissa S Monsey Kristie T Ota Irene F Akingbade Ellie S Hong Glenn E Schafe |
| author_sort | Melissa S Monsey |
| collection | DOAJ |
| description | Epigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA) in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC) inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM) is enhanced, while short-term memory (STM) is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT) inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP) at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA. |
| first_indexed | 2024-12-14T07:20:21Z |
| format | Article |
| id | doaj.art-cf59bfc0a0f340359f4ad2020d987521 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T07:20:21Z |
| publishDate | 2011-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-cf59bfc0a0f340359f4ad2020d9875212022-12-21T23:11:38ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0165e1995810.1371/journal.pone.0019958Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala.Melissa S MonseyKristie T OtaIrene F AkingbadeEllie S HongGlenn E SchafeEpigenetic mechanisms, including histone acetylation and DNA methylation, have been widely implicated in hippocampal-dependent learning paradigms. Here, we have examined the role of epigenetic alterations in amygdala-dependent auditory Pavlovian fear conditioning and associated synaptic plasticity in the lateral nucleus of the amygdala (LA) in the rat. Using Western blotting, we first show that auditory fear conditioning is associated with an increase in histone H3 acetylation and DNMT3A expression in the LA, and that training-related alterations in histone acetylation and DNMT3A expression in the LA are downstream of ERK/MAPK signaling. Next, we show that intra-LA infusion of the histone deacetylase (HDAC) inhibitor TSA increases H3 acetylation and enhances fear memory consolidation; that is, long-term memory (LTM) is enhanced, while short-term memory (STM) is unaffected. Conversely, intra-LA infusion of the DNA methyltransferase (DNMT) inhibitor 5-AZA impairs fear memory consolidation. Further, intra-LA infusion of 5-AZA was observed to impair training-related increases in H3 acetylation, and pre-treatment with TSA was observed to rescue the memory consolidation deficit induced by 5-AZA. In our final series of experiments, we show that bath application of either 5-AZA or TSA to amygdala slices results in significant impairment or enhancement, respectively, of long-term potentiation (LTP) at both thalamic and cortical inputs to the LA. Further, the deficit in LTP following treatment with 5-AZA was observed to be rescued at both inputs by co-application of TSA. Collectively, these findings provide strong support that histone acetylation and DNA methylation work in concert to regulate memory consolidation of auditory fear conditioning and associated synaptic plasticity in the LA.http://europepmc.org/articles/PMC3098856?pdf=render |
| spellingShingle | Melissa S Monsey Kristie T Ota Irene F Akingbade Ellie S Hong Glenn E Schafe Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. PLoS ONE |
| title | Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. |
| title_full | Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. |
| title_fullStr | Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. |
| title_full_unstemmed | Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. |
| title_short | Epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala. |
| title_sort | epigenetic alterations are critical for fear memory consolidation and synaptic plasticity in the lateral amygdala |
| url | http://europepmc.org/articles/PMC3098856?pdf=render |
| work_keys_str_mv | AT melissasmonsey epigeneticalterationsarecriticalforfearmemoryconsolidationandsynapticplasticityinthelateralamygdala AT kristietota epigeneticalterationsarecriticalforfearmemoryconsolidationandsynapticplasticityinthelateralamygdala AT irenefakingbade epigeneticalterationsarecriticalforfearmemoryconsolidationandsynapticplasticityinthelateralamygdala AT ellieshong epigeneticalterationsarecriticalforfearmemoryconsolidationandsynapticplasticityinthelateralamygdala AT glenneschafe epigeneticalterationsarecriticalforfearmemoryconsolidationandsynapticplasticityinthelateralamygdala |