Department of Pharmacology and Physiology, The George Washington University, Washington, DC, USA.
Sci Adv. 2020 Jun 12;6(24):eaba1430. doi: 10.1126/sciadv.aba1430. eCollection 2020 Jun.
GABAergic interneurons are proposed to be critical for early activity and synapse formation by directly exciting, rather than inhibiting, neurons in developing hippocampus and neocortex. However, the role of GABAergic neurons in the generation of neonatal network activity has not been tested in vivo, and recent studies have challenged the excitatory nature of early GABA. By locally manipulating interneuron activity in unanesthetized neonatal mice, we show that GABAergic neurons are excitatory in CA1 hippocampus at postnatal day 3 (P3) and are responsible for most of the spontaneous firing of pyramidal cells at that age. Hippocampal interneurons become inhibitory by P7, whereas visual cortex interneurons are already inhibitory by P3 and remain so throughout development. These regional and age-specific differences are the result of a change in chloride reversal potential, because direct activation of light-gated anion channels in glutamatergic neurons drives CA1 firing at P3, but silences it at P7 in CA1, and at all ages in visual cortex. This study in the intact brain reveals that GABAergic interneuron excitation is essential for network activity in neonatal hippocampus and confirms that visual cortical interneurons are inhibitory throughout early postnatal development.
GABA 能中间神经元被认为对早期活动和突触形成至关重要，它们通过直接兴奋神经元，而不是抑制神经元，在发育中的海马体和新皮层中起作用。然而，GABA 能神经元在新生儿网络活动产生中的作用尚未在体内得到测试，最近的研究也对早期 GABA 的兴奋性提出了挑战。通过在未麻醉的新生小鼠中局部操纵中间神经元活动，我们发现在出生后第 3 天（P3），CA1 海马体中的 GABA 能神经元具有兴奋性，并且在那个年龄段负责大多数锥体神经元的自发放电。海马体中间神经元在 P7 时变为抑制性，而视觉皮层中间神经元在 P3 时已经是抑制性的，并在整个发育过程中保持这种状态。这些区域和年龄特异性的差异是由于氯离子反转电位的变化所致，因为直接激活谷氨酸能神经元的光门控阴离子通道可在 P3 时驱动 CA1 放电，但在 P7 时在 CA1 中使其沉默，并且在视觉皮层的所有年龄段中均如此。这项在完整大脑中的研究表明，GABA 能中间神经元的兴奋对于新生儿海马体中的网络活动至关重要，并证实了视觉皮层中间神经元在整个新生后发育过程中都是抑制性的。
