Division of Basic Neuroscience, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA.
Division of Basic Neuroscience, McLean Hospital, Belmont, MA 02478, USA; Department of Psychiatry, Harvard Medical School, Boston, MA 02215, USA; School of Life Sciences, Ecole Polytechnique Federale de Lausanne, Lausanne CH-1015, Switzerland.
Neurosci Biobehav Rev. 2024 Jun;161:105651. doi: 10.1016/j.neubiorev.2024.105651. Epub 2024 Apr 4.
GABA is the primary inhibitory neurotransmitter in the adult brain and through its actions on GABARs, it protects against excitotoxicity and seizure activity, ensures temporal fidelity of neurotransmission, and regulates concerted rhythmic activity of neuronal populations. In the developing brain, the development of GABAergic neurons precedes that of glutamatergic neurons and the GABA system serves as a guide and framework for the development of other brain systems. Despite this early start, the maturation of the GABA system also continues well into the early postnatal period. In this review, we organize evidence around two scenarios based on the essential and protracted nature of GABA system development: 1) disruptions in the development of the GABA system can lead to large scale disruptions in other developmental processes (i.e., GABA as the cause), 2) protracted maturation of this system makes it vulnerable to the effects of developmental insults (i.e., GABA as the effect). While ample evidence supports the importance of GABA/GABAR system in both scenarios, large gaps in existing knowledge prevent strong mechanistic conclusions.
GABA 是成人脑中的主要抑制性神经递质，通过其对 GABAR 的作用，它可以防止兴奋毒性和癫痫发作，确保神经递质传递的时间保真度，并调节神经元群体的协调节律活动。在发育中的大脑中，GABA 能神经元的发育先于谷氨酸能神经元，GABA 系统作为其他脑系统发育的指导和框架。尽管如此，GABA 系统的成熟也会持续到出生后的早期阶段。在这篇综述中，我们根据 GABA 系统发育的本质和持久性这两个情景，围绕两个证据组织起来：1）GABA 系统发育的中断会导致其他发育过程的大规模中断（即 GABA 是原因），2）该系统的长期成熟使其容易受到发育损伤的影响（即 GABA 是结果）。虽然有大量证据表明 GABA/GABAR 系统在这两种情况下都很重要，但现有知识的巨大差距阻止了对机制的强有力结论。
