Emergence of Visual Alertness in Cortical Networks

描述（由申请人提供）：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，定义视觉在出生时及时“在线”的机制对于理解正常和病理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，以及产生视觉警觉性和注意力的皮层状态的发展。动物模型提供了对前者的机制理解，但由于缺乏未麻醉的动物模型，证明与胎儿和围产期人类皮质活动具有同源性，因此对警觉视觉反应动力学发展机制的深入了解受到限制。为了克服这一限制，我和我的合作者在行为幼鼠模型的表征上进行了重大投资，该模型再现了早期人类皮层活动的发展。我们建议使用该模型来确定驱动皮层警觉性发展的网络机制，并描述它们在围产期视觉反应功能成熟中的作用。在之前的研究中，我们发现人类在足月（出生）前23周，大鼠在睁眼前1-2天，视觉皮层活动迅速成熟。在这个开关之前，皮层的活动主要是由网络沉默所主导，偶尔会被自发或响应于光的大振幅振荡爆发所打断。成人清醒状态的典型警觉性的电图特征，即脑电图中的“激活”或“不同步”状态，即使在婴儿清醒的时候，也没有在这些年龄段观察到。当振荡爆发被快速的视觉反应所取代时，这一时期就会突然结束，这种反应叠加在清醒时激活的皮层状态上，我们称之为“视觉警觉性”。我们将检验这一假设，即视觉警觉性的出现是前驱皮层抑制快速发展的结果，是在睁眼前去甲肾上腺素（NE）释放激增的结果。我们的研究结果将为改变皮层网络特性如何影响视觉发育以及如何实现这些特性的个体发生控制提供新的理解。我们希望这一信息将有助于诊断和治疗中枢性视觉和注意力缺陷普遍存在于早产儿和其他儿童

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.