Emergence of Visual Alertness in Cortical Networks

描述(申请人提供)：人类新生儿使用视觉来指导行为，形成照顾者依恋，并建立更复杂的视觉和认知能力。因此，对于理解正常和病理性视觉处理的发展，定义视觉在出生前及时在线的机制是必不可少的。视觉感知需要有组织的接受区的发展，以及产生视觉警觉和注意力的皮质状态的发展。动物模型提供了对前者的机制理解，但由于缺乏与胎儿和围产期人类皮质活动具有同源性的未麻醉动物模型，对警觉视觉反应动力学形成的机制的洞察一直受到限制。为了克服这一局限，我和我的合作者们在描述一种行为幼鼠模型方面投入了大量资金，该模型概括了早期人类皮质活动的发展。我们建议使用这个模型来识别驱动大脑皮质警觉性发展的网络机制，并表征它们在围产期内脏反应功能成熟中的作用。在先前的研究中，我们发现人的视觉皮质活动在足月(出生)前23周和大鼠睁眼前1-2天迅速成熟。在这种转换之前，大脑皮层活动由网络静默主导，并被不常见的、大幅度的振荡爆发所打断，这些振荡爆发既自发地发生，也对光作出反应。成人清醒状态的典型电信号特征，即脑电中的“激活”或“不同步”状态，在这些年龄段并不能观察到，即使婴儿显然是清醒的。这一时期突然结束，在清醒状态下，振荡爆发被叠加在激活的大脑皮层状态上的快速视觉反应所取代，这就是我们所说的“视觉警觉”。我们将检验这一假说，视觉警觉性的出现是前馈皮质抑制快速发展的结果，而去甲肾上腺素(NE)释放激增发生在睁开眼睛之前。我们的结果将为我们提供一个新的理解，了解皮层网络属性的变化如何影响视觉的发育，以及这些属性的个体发育控制是如何实现的。我们期望这一信息将有助于诊断和治疗在早产儿和其他疾病中普遍存在的中枢视觉和注意力缺陷。 有风险的婴儿。

DESCRIPTION (provided by applicant): Human neonates use vision to guide behavior, form caregiver attachments, and build more complex visual and cognitive abilities. Defining the mechanisms by which vision comes 'online' in time for birth is thus essential to understand the development of normal and pathological visual processing. Visual perception requires the development of organized receptive fields as well as the development of cortical states that generate visual alertness and attention. Animal models have provided a mechanistic understanding of the former, but insight into the mechanisms by which alert visual response dynamics develop has been limited by a paucity of unanesthetized animal models with demonstrated homology to fetal and perinatal human cortical activity. To overcome this limitation, my collaborators and I have made a significant investment in the characterization of a behaving infant rat model that recapitulates early human cortical activity development. We propose to use this model to identify the network mechanisms that drive the development of cortical alertness, and characterize their role in the perinatal functional maturation of the visua response. In prior studies we identified a rapid maturation of visual cortical activity occurring 23 weeks before term (birth) in humans and 1-2 days before eye opening in rats. Before this switch cortical activity is dominated by network silence, interrupted by infrequent, large amplitude oscillatory bursts that occur both spontaneously and in response to light. The electrographic signature of alertness typical of the adult waking state, namely the "activated" or "desynchronized" state in the EEG, is not observed at these ages even when the infant is clearly awake. This period ends suddenly when oscillatory bursts are replaced by fast visual responses superimposed on an activated cortical state during wakefulness, which we call "visual alertness". We will test the hypothesis the emergence of visual alertness is the result of rapid development of feed-forward cortical inhibition and a surge in norephinephrine (NE) release occurring just before eye opening. Our results will provide a novel understanding of how changing cortical network properties influence development of vision, and how ontogenetic control of the timing of these properties is achieved. We expect this information will inform the diagnosis and treatment of central visual and attention deficits prevalent in pre-term and other at risk infants.