Emergence of Visual Alertness in Cortical Networks

描述（由申请人提供）：人类新生儿使用视觉指导行为，形成看护者依恋，并建立更复杂的视觉和认知能力。因此，定义视觉在出生时“在线”的机制对于理解正常和病理性视觉处理的发展至关重要。视觉感知需要有组织的感受野的发展，以及产生视觉警觉和注意力的皮层状态的发展。动物模型提供了一个机械的理解前者，但洞察警觉的视觉反应动力学发展的机制一直受到限制，缺乏未麻醉的动物模型与胎儿和围产期人类皮质活动的同源性。为了克服这一局限性，我和我的合作者在行为幼年大鼠模型的表征方面进行了重大投资，该模型重现了早期人类皮层活动的发展。我们建议使用这个模型来识别驱动皮层警觉性发展的网络机制，并描述其在围产期视觉反应功能成熟中的作用。在先前的研究中，我们发现人类在足月（出生）前23周和大鼠在睁眼前1-2天出现视觉皮层活动的快速成熟。在这个开关之前，皮层活动由网络沉默主导，被自发发生的和响应于光的罕见的大幅度振荡突发中断。成人清醒状态的典型警觉性电图特征，即EEG中的“激活”或“去激活”状态，在这些年龄段甚至当婴儿明显清醒时也没有观察到。当振荡爆发被快速视觉反应所取代时，这一时期突然结束，这种快速视觉反应叠加在清醒时激活的皮层状态上，我们称之为“视觉警觉”。我们将检验这一假设，即视觉警觉性的出现是前馈皮层抑制快速发展和睁眼前去甲肾上腺素（NE）释放激增的结果。我们的研究结果将提供一个新的理解如何改变皮层网络属性影响视力的发展，以及如何实现这些属性的时间的个体发育控制。我们希望这些信息将为早产儿和其他早产儿普遍存在的中枢视觉和注意力缺陷的诊断和治疗提供信息。 风险婴儿

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.