Shen Jing, Colonnese Matthew T
Department of Pharmacology and Physiology, Washington, DC 20037.
Department of Pharmacology and Physiology, Washington, DC 20037
J Neurosci. 2016 Nov 30;36(48):12259-12275. doi: 10.1523/JNEUROSCI.1903-16.2016.
A comprehensive developmental timeline of activity in the mouse cortex in vivo is lacking. Understanding the activity changes that accompany synapse and circuit formation is important to understand the mechanisms by which activity molds circuits and would help to identify critical checkpoints for normal development. To identify key principles of cortical activity maturation, we systematically tracked spontaneous and sensory-evoked activity with extracellular recordings of primary visual cortex (V1) in nonanesthetized mice. During the first postnatal week (postnatal days P4-P7), V1 was not visually responsive and exhibited long (>10 s) periods of network silence. Activation consisted exclusively of "slow-activity transients," 2-10 s periods of 6-10 Hz "spindle-burst' oscillations; the response to spontaneous retinal waves. By tracking daily changes in this activity, two key components of spontaneous activity maturation were revealed: (1) spindle-burst frequency acceleration (eventually becoming the 20-50 Hz broadband activity caused by the asynchronous state) and (2) "filling-in" of silent periods with low-frequency (2-4 Hz) activity (beginning on P10 and complete by P13). These two changes are sufficient to create the adult-like pattern of continuous activity, alternation between fast-asynchronous and slow-synchronous activity, by eye opening. Visual responses emerged on P8 as evoked spindle-bursts and neuronal firing with a signal-to-noise ratio higher than adult. Both were eliminated by eye opening, leaving only the mature, short-latency response. These results identify the developmental origins of mature cortical activity and implicate the period before eye opening as a critical checkpoint. By providing a systematic description of electrical activity development, we establish the murine visual cortex as a model for the electroencephalographic development of fetal humans.
Cortical activity is an important indicator of long-term health and survival in preterm infants and molds circuit formation, but gaps remain in our understanding of the origin and normal progression of this activity in the developing cortex. We aimed to rectify this by monitoring daily changes in cortical activity in the nonanesthetized mouse, an important preclinical model of disease and development. At ages approximately equivalent to normal human term birth, mouse cortex exhibits primarily network silence, with spontaneous "spindle bursts" as the only form of activity. In contrast, mature cortex is noisy, alternating between asynchronous/discontinuous and synchronous/continuous states. This work identifies the key processes that produce this maturation and provides a normative reference for murine-based studies of cortical circuit development.
目前尚缺乏对小鼠皮层体内活动的全面发育时间表。了解伴随突触和神经回路形成的活动变化对于理解活动塑造神经回路的机制非常重要，并且有助于确定正常发育的关键检查点。为了确定皮层活动成熟的关键原则，我们在未麻醉的小鼠中通过细胞外记录系统地跟踪初级视觉皮层（V1）的自发活动和感觉诱发活动。在出生后的第一周（出生后第4 - 7天），V1没有视觉反应，并且表现出长时间（>10秒）的网络沉默。激活完全由“慢活动瞬变”组成，即2 - 10秒的6 - 10赫兹“纺锤波爆发”振荡；这是对自发视网膜波的反应。通过跟踪这种活动的每日变化，揭示了自发活动成熟的两个关键组成部分：（1）纺锤波爆发频率加速（最终变为由异步状态引起的20 - 50赫兹宽带活动）和（2）用低频（2 - 4赫兹）活动“填充”沉默期（从出生后第10天开始并在出生后第13天完成）。这两个变化足以在睁眼时产生类似成年的连续活动模式，即快速异步和慢速同步活动之间的交替。视觉反应在出生后第8天以诱发的纺锤波爆发和神经元放电的形式出现，其信噪比高于成年期。两者在睁眼时都被消除，只留下成熟的短潜伏期反应。这些结果确定了成熟皮层活动的发育起源，并表明睁眼之前的时期是一个关键检查点。通过提供电活动发育的系统描述，我们将小鼠视觉皮层确立为胎儿人类脑电图发育的模型。
皮层活动是早产儿长期健康和生存的重要指标，并且塑造神经回路形成，但我们对发育中的皮层中这种活动的起源和正常进展的理解仍存在差距。我们旨在通过监测未麻醉小鼠皮层活动的每日变化来纠正这一点，未麻醉小鼠是疾病和发育的重要临床前模型。在大约相当于人类正常足月出生的年龄，小鼠皮层主要表现为网络沉默，自发的“纺锤波爆发”是唯一的活动形式。相比之下，成熟皮层是嘈杂的，在异步/不连续和同步/连续状态之间交替。这项工作确定了产生这种成熟的关键过程，并为基于小鼠的皮层神经回路发育研究提供了规范性参考。
