title: DNA methylation regulates associative reward learning.
abstract: Reward-related memories are essential for adaptive behavior and evolutionary fitness, but they are also a core component of maladaptive brain diseases such as addiction. Reward learning requires dopamine neurons located in the ventral tegmental area (VTA), which encode relationships between predictive cues and future rewards. Recent evidence suggests that epigenetic mechanisms, including DNA methylation, are essential regulators of neuronal plasticity and experience-driven behavioral change. However, the role of epigenetic mechanisms in reward learning is poorly understood. Here we show that the formation of reward-related associative memories in rats upregulates key plasticity genes in the VTA, which are correlated with memory strength and associated with gene-specific changes in DNA methylation. Moreover, DNA methylation in the VTA is required for the formation of stimulus-reward associations. These results provide the first evidence that that activity-dependent methylation and demethylation of DNA is an essential substrate for the behavioral and neuronal plasticity driven by reward-related experiences.
authors: 1] Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama, USA. [2] Evelyn F. McKnight Brain Institute, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors: Jeremy J
authors: JJ
authors: Day
authors: Daniel
authors: D
authors: Childs
authors: Mikael C
authors: MC
authors: Guzman-Karlsson
authors: Mercy
authors: M
authors: Kibe
authors: Jerome
authors: J
authors: Moulden
authors: Esther
authors: E
authors: Song
authors: Absar
authors: A
authors: Tahir
authors: J David
authors: JD
authors: Sweatt
mesh_terms: D000818:Animals; D001245:Association Learning / Q000502:physiology*; D002478:Cells, Cultured; D003213:Conditioning, Psychological / Q000502:physiology*; D019175:DNA Methylation / Q000235:genetics*; D059290:Dopaminergic Neurons / Q000378:metabolism; D008297:Male; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
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