权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mechanisms regulating the maturation of prefrontal top-down circuitry in control of attentional behavior

控制注意力行为的前额叶自上而下电路成熟的调节机制

基本信息

批准号：
9973170
负责人：
Hirofumi Morishita
金额：
$ 58.05万
依托单位：
ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-05 至 2024-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9973170
关键词：
Adolescence Adolescent Adult Animals Anterior Area Attention Attentional deficit Behavior Behavioral Brain Calcium Childhood Cognitive Data Development Diagnosis Discrimination Disease Distal Equilibrium FMR1 FMRP Fiber Fragile X Syndrome Frequencies Gene Expression Genes Goals Image Intervention Knowledge Macaca Maps Measures Mediating Mental disorders Methods Molecular Motor Mus Neurodevelopmental Disorder Neurons Photometry Prefrontal Cortex Process Rabies Reaction Time Reporting Role Sensory Slice System Techniques Testing Viral Visual Visual Cortex Visual attention attentional control base cingulate cortex cognitive function cohesion extrastriate visual cortex improved in vivo insight knock-down neuropsychiatric disorder optogenetics overexpression patch clamp relating to nervous system response risk variant touchscreen transcriptome visual stimulus

项目摘要

Cognitive function relies on the cohesive activity of large-scale networks. Long-range cortico-cortical projections facilitate such network activities by integrating information from various inputs and then relaying it to other cortical regions. Of particular significance is the evolutionarily conserved top-down projection from prefrontal cortex (PFC) to sensory visual cortex (VIS) which integrates sensory, motor, and cognitive information to modulate sensory processing. Conserved PFC->VIS projections regulate VIS responses to visual stimuli in attention based tasks in macaque, and optogenetic manipulation in mice shows that this circuit can enhance visual discrimination sensitivity. Notably, deficits in PFC modulation of VIS activity are pervasively reported in neurodevelopmental and psychiatric disorders, and often emerge following childhood and adolescence. Yet limited knowledge of processes governing long-range cortical circuit development hinders further pathophysiological insight into these conditions. The goal of this study is to identify the developmental mechanisms of PFC circuitry that mediate top-down control of attentional network and behavior. Here we test the hypothesis that top-down PFC->VIS cortical circuits require a Lynx1, developmentally regulated nicotinic modulator,-dependent adolescent shift in the balance of local/long-range inputs to coordinate temporal dynamics between PFC and VIS modulate attentional behavior, and that Lynx1 modulation can ameliorate top- down circuit deficits in mice with a risk gene of neurodevelopmental disorders. We will test his hypothesis by integrating techniques to measure and manipulate neural activity and gene expression within specific circuits of mice tested in a translationally-relevant touchscreen system to assess attention during naturalistic freely- moving behavior.

认知功能依赖于大规模网络的内聚活动。远程cortico-cortical