A central goal of neuroscience research is to understand how experiences modify brain circuits to guide future adaptive behavior. In response to environmental stimuli, neural circuit activity engages gene regulatory mechanisms within each cell. This activity-dependent gene expression is governed, in part, by epigenetic processes that can produce persistent changes in both neural circuits and the epigenome itself. The complex interplay between circuit activity and neuronal gene regulation is vital to learning and memory, and, when disrupted, is linked to debilitating psychiatric conditions, such as substance use disorder. To develop clinical treatments, it is paramount to advance our understanding of how neural circuits and the epigenome cooperate to produce behavioral adaptation. Here, we discuss how new genetic tools, used to manipulate neural circuits and chromatin, have enabled the discovery of epigenetic processes that bring about long-lasting changes in behavior relevant to mental health and disease.

神经科学研究的一个中心目标是了解经验如何改变大脑回路以指导未来的适应性行为。为了响应环境刺激，神经回路活动涉及每个细胞内的基因调节机制。这种活动依赖性基因表达部分受到表观遗传过程的控制，表观遗传过程可以在神经回路和表观基因组本身中产生持续的变化。回路活动和神经元基因调节之间复杂的相互作用对于学习和记忆至关重要，当受到干扰时，可能与药物滥用等精神疾病有关。为了开发临床治疗方法，最重要的是加深我们对神经回路和表观基因组如何合作产生行为适应的理解。在这里，我们讨论用于操纵神经回路和染色质的新遗传工具如何发现表观遗传过程，从而带来与心理健康和疾病相关的行为的持久变化。