Bruel-Jungerman Elodie, Rampon Claire, Laroche Serge
Laboratoire de Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, CNRS UMR 8620, University Paris-Sud, Orsay, France.
Rev Neurosci. 2007;18(2):93-114. doi: 10.1515/revneuro.2007.18.2.93.
The demonstration that progenitor cells in regions of the adult mammalian brain such as the dentate gyrus of the hippocampus can undergo mitosis and generate new cells that differentiate into functionally integrated neurons throughout life has marked a new era in neuroscience. In recent years, a wide range of investigations has been directed at understanding the physiological mechanisms and functional relevance of this form of brain plasticity. Our current knowledge of adult hippocampal neurogenesis indicates that the production of new cells in the brain follows a multi-step process during which newborn cells are submitted to various regulatory factors that influence cell proliferation, maturation, fate determination and survival. As details of the dynamics of morphological maturation and functional integration of newborn neurons in corticohippocampal circuits have become clearer, an increasing number of studies have examined how environmental and/or behavioural factors can modulate neurogenesis and affect hippocampal-dependent learning and memory. In this article we present an overview of recent literature that relates neurogenesis to hippocampal function on the basis of correlative studies investigating the modulation of neurogenesis by learning and behavioural experience, and the consequences of the loss of hippocampal neurogenesis for memory function. We also highlight experimental evidence that immature neurons exhibit unique electrophysiological characteristics and therefore may constitute a specific cell population particularly inclined to undergo activity-dependent plasticity. Moreover, we review recent work that reveals an unsuspected mechanistic link between synaptic plasticity and the proliferation and survival of new hippocampal neurons. From the present background of research, we argue that the incorporation of functional adult-generated neurons into existing neural networks provides a higher capacity for plasticity, which may favour the encoding and storage of certain types of memories. Depending on their birth date and maturation stage, new neurons might be implicated in the encoding/storage process of the task at hand or may help future learning experience. Finally, we highlight critical issues to be addressed in order to decipher the exact contribution of newly generated neurons to cognitive functions.
成年哺乳动物大脑区域(如海马齿状回)中的祖细胞能够进行有丝分裂并产生新细胞,这些新细胞在整个生命过程中分化为功能整合的神经元,这一发现标志着神经科学进入了一个新时代。近年来,人们进行了广泛的研究,旨在了解这种大脑可塑性形式的生理机制和功能相关性。我们目前对成年海马神经发生的认识表明,大脑中新细胞的产生遵循一个多步骤过程,在此过程中,新生细胞受到各种调节因子的影响,这些因子会影响细胞增殖、成熟、命运决定和存活。随着新生成神经元在皮质 - 海马回路中形态成熟和功能整合动态细节的日益清晰,越来越多的研究探讨了环境和/或行为因素如何调节神经发生并影响海马依赖性学习和记忆。在本文中,我们基于相关研究概述了近期文献,这些研究调查了学习和行为经验对神经发生的调节作用,以及海马神经发生丧失对记忆功能的影响。我们还强调了实验证据,即未成熟神经元表现出独特的电生理特征,因此可能构成一个特别倾向于经历活动依赖性可塑性的特定细胞群体。此外,我们回顾了近期的研究工作,这些工作揭示了突触可塑性与新海马神经元增殖和存活之间意想不到的机制联系。从当前的研究背景来看,我们认为将成年产生的功能性神经元纳入现有神经网络可提供更高的可塑性能力,这可能有利于某些类型记忆的编码和存储。根据它们的出生日期和成熟阶段,新神经元可能参与手头任务的编码/存储过程,或者可能有助于未来的学习经验。最后,我们强调了为破译新生成神经元对认知功能的确切贡献而需要解决的关键问题。