Over the last two decades, the explosion of experimental, computational, and high-throughput technologies has led to critical insights into how the brain functions in health and disease. It has become increasingly clear that the vast majority of brain activities result from the complex entanglement of genetic factors, epigenetic changes, and environmental stimuli, which, when altered, can lead to neurodegenerative and neuropsychiatric disorders. Nevertheless, a complete understanding of the molecular mechanisms underlying neuronal activities and higher-order cognitive processes continues to elude neuroscientists. Here, we provide a concise overview of how the interaction between the environment and genetic as well as epigenetic mechanisms shapes complex neuronal processes such as learning, memory, and synaptic plasticity. We then consider how this interaction contributes to the development of neurodegenerative and psychiatric disorders, and how it can be modeled to predict phenotypic variability and disease risk. Finally, we outline new frontiers in neurogenetic and neuroepigenetic research and highlight the challenges these fields will face in their quest to decipher the molecular mechanisms governing brain functioning.

在过去的二十年中，实验，计算和高通量技术的爆炸式增长带来了关于大脑在健康和疾病中的功能的重要见解。越来越清楚的是，绝大多数大脑活动是由遗传因素，表观遗传学变化和环境刺激的复杂纠缠所引起的，这些疾病一旦改变，就会导致神经退行性疾病和神经精神疾病。尽管如此，对神经元活动和更高阶认知过程的分子机制的完整理解仍在继续使神经科学家望而却步。在这里，我们简要概述了环境与遗传和表观遗传机制之间的相互作用如何形成复杂的神经元过程，例如学习，记忆和突触可塑性。然后，我们考虑这种相互作用如何促进神经退行性疾病和精神疾病的发展，以及如何对其进行建模以预测表型变异性和疾病风险。最后，我们概述了神经遗传学和神经表观遗传学研究的新领域，并着重指出了这些领域在寻求解释控制脑功能的分子机制方面将面临的挑战。