Histone H3 Acetylation is Asymmetrically Induced Upon Learning in Identified Neurons of the Food Aversion Network in the Mollusk Helix Lucorum

Abstract

Regulation of gene expression is an essential step during long-term memory formation. Recently, the involvement of DNA-binding transcription factors and chromatin remodeling in synaptic plasticity have been intensively studied. The process of learning was shown to be associated with chromatin remodeling through histone modifications such as acetylation and phosphorylation. We have previously shown that the MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase) regulatory cascade plays a key role in the food aversion conditioning in the mollusk Helix. Specifically, command neurons of withdrawal behavior exhibit a learning-dependent asymmetry (left–right) in MAPK/ERK activation. Here, we expanded our molecular studies by focusing on a potential MAPK/ERK target – histone H3. We studied whether there is a learning-induced MAPK/ERK-dependent acetylation of histone H3 in command neurons RPa(2/3) and LPa(2/3) of the right and left parietal ganglia and whether it is asymmetrical. We found a significant learning-dependent increase in histone H3 acetylation in RPa(2/3) neurons but not in LPa(2/3) neurons. Such an increase in right command neurons depended on MAPK/ERK activation and correlated with a lateralized avoidance movement to the right visible 48 h after training. The molecular changes found in a selective set of neurons could thus represent a lateralized memory process, which may lead to consistent turning in one direction when avoiding a food that has been paired with an aversive stimulus.

Epigenetic regulation of memory formation and maintenance

“…In addition, histone modifications may be important for the consolidation of conditioned taste aversion (CTA) memories. Studies in the mollusk Helix lucorum show unilateral increases in H3K14 acetylation in premotor interneurons that initiate withdrawal behavior in response to a food item previously paired with an aversive electric shock (Danilova et al 2010). In rodents, a role for histone acetylation in CTA memory is indirectly supported by increased levels of lysine-HAT activity in the insular cortex after training (Swank and Sweatt 2001).…”

The Role of Histone Acetylation in Memory Formation and Cognitive Impairments

“…Although overexpression of HDAC1 does not disrupt initial memory consolidation, it has been recently shown to affect fear extinction (Bahari-Javan et al, 2012). Downregulation of HDAC3 using genetic and pharmacological (Guan et al, 2002) Not reduced in CBP mutant mice (Alarcon et al, 2004) Induced in hippocampal slices after FSK and PDA (K14, Chwang et al, 2007) Induced after CFC 1 h but not 24 h (Levenson et al, 2004) Induced after cued fear conditioning in amygdala (Monsey et al, 2011) Induced at Nr4a2 and Nr4a1 promoter after CFC+TSA (Vecsey et al, 2007) Induced upon learning in food aversion in mollusks (Danilova et al, 2010) K9, K14: induced 1 h after CFC (Peleg et al, 2010) K9, K14 induced after MWM (both visible and hidden) (Bousiges et al, 2010) K9, K14 induced after BDNF treatment (Calfa et al, 2011) K14 decreased in CBP focal KO Reduced in CBP mutant mice (Valor et al, 2011) H4 K5, K8, K12, K16, K20…”

“…Normal aging-related memory impairment is associated with the lack of histone H4 acetylation, which can be rescued by treatment with KDAC inhibitors to restore memory function (Peleg et al, 2010). Histone acetylation has also been shown to be induced after food aversion training in mollusks (Danilova et al, 2010), and overexpression as well as RNAi-mediated knockdown of histone deacetylase Rpd3 has been shown to impair longterm memory in Drosophila (Fitzsimons and Scott, 2011). Thus, the evidence argues that histone acetylation is a general mechanism of memory storage.…”

Opposite roles of serotonin and neuropeptide FMRFamide in the regulation of epigenetic processes involved in the longterm memory formation

“…Показано, что эпигенетические модификации гистонов вовлекаются и в формирование долговременной памяти (Levenson, Sweatt, 2006;Wood et al, 2006;Danilova et al, 2010;Gupta et al, 2010;Гринкевич, 2012а, б;Danilova, Grinkevich, 2012;Kandel, 2012). В настоящее время наиболее интенсивно изучается ацетилирование и мети-лирование гистонов, так как показана принципиальная возможность через воздействие на эти процессы влиять на ментальные характеристики, нарушенные в ряде пато-логий (Abel, Zukin, 2008;Kurita et al, 2012).…”

“…Ранее мы показали, что MAPK / ERK активируется при о бучении Helix, и эта активация серотонин-зависима (Grinkevich et al, 2008). Блокада MAPK / ERK каскада приводит к неспособ-ности формирования ДП и сопровождается снижением ацетилирования гистона Н3, индуцируемого обучением (Danilova et al, 2010;Гринкевич, 2012а;Danilova, Grinkevich, 2012). Известно, что MAPK / ERK каскад играет важную роль в индукции ацетилирования через актива-цию ацетилтрансфераз фосфорилированием (Гринкевич, 2012а).…”