Cooper Daniel D, Frenguelli Bruno G
School of Life Sciences, University of Warwick, Coventry, UK.
School of Life Sciences, University of Warwick, Coventry, UK.
Neuropharmacology. 2021 Aug 1;193:108620. doi: 10.1016/j.neuropharm.2021.108620. Epub 2021 May 26.
The ability of glutamatergic synaptic strength to change in response to prevailing neuronal activity is believed to underlie the capacity of animals, including humans, to learn from experience. This learning better equips animals to safely navigate challenging and potentially harmful environments, while reinforcing behaviours that are conducive to survival. Early descriptions of the influence of experience on behaviour were provided by Donald Hebb who showed that an enriched environment improved performance of rats in a variety of behavioural tasks, challenging the widely-held view at the time that psychological development and intelligence were largely predetermined through genetic inheritance. Subsequent studies in a variety of species provided detailed cellular and molecular insights into the neurobiological adaptations associated with enrichment and its counterparts, isolation and deprivation. Here we review those experience-dependent changes that occur at the glutamatergic synapse, and which likely underlie the enhanced cognition associated with enrichment. We focus on the importance of signalling initiated by the release of BDNF and a prime downstream effector, MSK1, in orchestrating the many structural and functional neuronal adaptations associated with enrichment. In particular we discuss the MSK1-dependent expansion of the dynamic range of the glutamatergic synapse, which may allow enhanced information storage or processing, and the establishment of a genomic homeostasis that may both stabilise the enriched brain, and may make it better able to respond to novel experiences.
谷氨酸能突触强度根据当前神经元活动发生变化的能力，被认为是包括人类在内的动物从经验中学习的能力基础。这种学习能让动物更好地在充满挑战和潜在危险的环境中安全导航，同时强化有利于生存的行为。唐纳德·赫布最早描述了经验对行为的影响，他发现丰富的环境能提高大鼠在各种行为任务中的表现，挑战了当时广泛持有的观点，即心理发展和智力在很大程度上是由基因遗传预先决定的。随后在各种物种中的研究，对与丰富环境及其对应物（隔离和剥夺）相关的神经生物学适应提供了详细的细胞和分子见解。在这里，我们回顾那些发生在谷氨酸能突触处的依赖经验的变化，这些变化可能是与丰富环境相关的认知增强的基础。我们关注由脑源性神经营养因子（BDNF）释放引发的信号传导以及主要下游效应器丝裂原和应激激活蛋白激酶1（MSK1）在协调与丰富环境相关的许多结构和功能神经元适应中的重要性。特别是，我们讨论了MSK1依赖的谷氨酸能突触动态范围的扩展，这可能允许增强信息存储或处理，以及建立一种基因组稳态，这既可能稳定丰富环境下的大脑，又可能使其更好地应对新的经验。
