Table 2.
Dynamic histone modifications in animal models of fear/anxiety.
| Species | Paradigm | Measurement Post-training | Brain Region | Genomic Region | Histone Modification | Additional Findings | References |
|---|---|---|---|---|---|---|---|
| Rat | CFC and exposure alone | 1 h | Hip (CA1) | Genome-wide | H3K9me2↑ H3K4me3↑ | - | Gupta-Agarwal et al., 2012 [45] |
| Rat | CFC and exposure alone | 1 h | EC | Genome-wide | H3K9me2↑ H3K4me3↑ | - | Gupta-Agarwal et al., 2012 [45] |
| Rat | CFC and exposure alone | 24 h | EC | Genome-wide | H3K4me3↓ | - | Gupta-Agarwal et al., 2012 [45] |
| Rat | CFC and exposure alone | 1 h 24 h |
Hip (CA1) | Genome-wide | H3K9me2↑ H3K9me2↓ |
- | Gupta et al., 2010 [43] |
| Rat | CFC | 1 h | Hip (CA1) | Genome-wide | H3K4me3↑ | Returned to baseline after 24h |
Gupta et al., 2010 [43] |
| Mouse | CFC | 1 h | Hip (CA1), ACC | Genome-wide | H3K9ac↑ H3K4me3↑ H3K27me3↓ |
DNAme↓ (ACC) | Halder et al., 2016 [42] |
| Rat | CFC | 1 h | Hip (CA1) | Genome-wide | H3K14ac↑ | Returned to baseline after 24 h | Levenson et al., 2004 [46] |
| Mouse | CFC | 1 h | Hip | Genome-wide | H4K5ac↑ | Lasting for 2-4 h depending on the amount of training |
Park et al., 2013 [47] |
| Rat | CFC | Immediately | Hip | Genome-wide | H2BK5ac↑ H3K9K14ac↑ H4K12ac↑ | - | Bousiges et al., 2013 [48] |
| Rat | CFC (SPS) | 2 h | Hip | Bdnf promoter I and IV | H3ac↑ H4ac↑ |
Bdnf mRNA↑ | Takei et al., 2011 [52] |
| Rat | CFC | 2 h | Hip (CA1) |
Bdnf promoter IV Bdnf promoter II |
H3ac↑, H3phospho-ac↑ H4ac↓ |
Bdnf exon IV mRNA↑ DNAme at Bdnf exons I and IV↓ DNAme at Bdnf exon VI↑ |
Lubin et al., 2008 [53] |
| Rat | Memory retrieval after CFC | 1 h | Hip (CA1), BLA |
Genome-wide | H3K4me3↑ (CA1) H3K9me2↑ (BLA) |
H3K4me3 returned to baseline after 24 h 5hmC↑ (CA1) |
Webb et al., 2017 [44] |
| Rat | Memory retrieval after CFC | 1 h | Hip (CA1) | Npas4 | H3K4me3↑ | 5hmC↑ | Webb et al., 2017 [44] |
| Rat | Memory retrieval after CFC | 30 days | ACC | C-fos | H3K4me3↑ | 5hmC↑ | Webb et al., 2017 [44] |
| Rat | AFC | 1 h | Lateral amygdala | Genome-wide | H3K9me2↑ | G9a mRNA↓ | Gupta-Agarwal et al., 2014 [54] |
| Rat | AFC | 24 h | Lateral amygdala |
Genome-wide | H3K9me2↓ | - | Gupta-Agarwal et al., 2014 [54] |
| Mouse | AFC | 26 h | PFC | Bdnf promoter I and IV | H3ac↑ | - | Bredy et al., 2007 [55] |
| Mouse | AFC + extinction | 2 h | PFC | Bdnf promoter I | H3ac↓ | Bdnf I and IV mRNA↑ | Bredy et al., 2007 [55] |
| Mouse | AFC + extinction | 2 h | PFC | Bdnf promoter IV | H4ac↑ | Bdnf I and IV mRNA↑ | Bredy et al., 2007 [55] |
| Rat | Fear memory (5x CS+US) |
2 h | PFC, amygdala | Genome-wide | H3ac↑ and H4ac↑ in BA, LA, CeM, CeL, PL-PFC | C-fos + CBP expression↑ | Siddiqui et al., 2017 [56] |
| Rat | Extinction | Immediately | PFC, amygdala | Genome-wide | H3ac↑ in IL-PFC and PL-PFC H4ac↑ in IL-PFC |
C-fos + CBP expression↑ | Siddiqui et al., 2017 [56] |
| Rat | Fear memory (5x CS+US) |
2 h | STMA, STLV (neurons) |
Genome-wide | H3ac↑, H4ac↑ | CBP↑ | Ranjan et al., 2017 [57] |
| Rat | Extinction | Immediately | STLP (neurons) |
Genome-wide | H3ac↑, H4ac↑ | CBP↑ | Ranjan et al., 2017 [57] |
| Rat | Immediate fear extinction (10 min) |
2 h | IL-PFC, PLC |
Genome-wide | PLC: H3K9ac↑ IL-PFC: H3K9ac↑ |
Retention of fear extinction↓ PLC: c-Fos↑ IL-PFC: c-Fos↑ PLC: CBP↑ IL-PFC: CBP↑ |
Singh et al., 2018 [58] |
| Rat | Delayed fear extinction (24 h) |
2 h | IL-PFC, PLC |
Genome-wide | PLC: H3K9ac↑ IL-PFC: H3K9ac↑↑ |
Retention of fear extinction↑ PLC: c-Fos↑ IL-PFC: c-Fos↑ PLC: CBP↑ IL-PFC: CBP↑↑ |
Singh et al., 2018 [58] |
Abbreviations: ACC: Anterior cingulate cortex, AFC: Auditory fear conditioning, Bdnf: Brain Derived Neurotrophic Factor, BLA: Basolateral amygdala, CA1: First region in the hippocampal circuit, CBP: CREB-binding protein, CFC: Contextual fear conditioning, C-fos: Proto-oncogene, CS: Conditioned stimulus, EC: Entorhinal cortex, G9a: Euchromatin histone-lysine N-methyltransferase 2 (EHMT2), Hip: Hippocampus, IL-PFC: Infralimbic prefrontal cortex, Npas4: Neuronal PAS Domain Protein 4, PFC: Prefrontal cortex, PLC: Prelimbic cortex, SPS: Single prolonged stress, STLP: Antero-lateral bed nucleus of the stria terminalis, STLV: Lateral-ventral bed nucleus of the stria terminalis, STMA: Antero-medial bed nucleus of the stria terminalis, UCS: Unconditioned stimulus.