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Cholinergic Mechanisms in Spatial Attention

空间注意力的胆碱能机制

基本信息

批准号：
9109455
负责人：
Anita A Disney
金额：
$ 24.9万
依托单位：
VANDERBILT UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-05-01 至 2017-10-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9109455
关键词：
Acetylcholine Achievement Address Affect Agonist Anatomy Area Arousal Attention Attention deficit hyperactivity disorder Attentional deficit Autistic Disorder Award Axon Basic Science Behavioral Behavioral Model Biological Sciences Caliber Cells Chemicals Cholinergic Receptors Clinical Cognition Cognitive Cognitive deficits Complement Data Dementia Disease Electric Stimulation Employee Strikes Environment Etiology Event Failure Fostering Foundations Functional disorder Genetic Goals Human Impairment Institutes Intervention Learning Measures Mediating Mental disorders Mentors Methods Modeling Mood Disorders Mus Neuromodulator Neurons Neurosciences Perception Pharmacology Phase Photic Stimulation Physiological Physiology Positioning Attribute Primates Process Protocols documentation Receptor Cell Research Resolution Rodent Role Schizophrenia Specificity Structure System Techniques Technology Testing Time Tissues Training Work abstracting area MT area V1 awake basal forebrain base career cell type cholinergic clinical practice cognitive function executive function gamma-Aminobutyric Acid in vivo information processing innovation insight mouse model neocortical neuropathology neuroregulation nonhuman primate optogenetics professional atmosphere public health relevance receptor receptor function research study selective attention sensory cortex sensory input skills stimulus processing stimulus sensitivity tenure track

项目摘要

Abstract Studying the normal functions and mechanisms of perception and attention is essential to identifying and understanding the failures in information processing and cognition that are aspects of many neuropathologies. Cognitive and attentional deficits are seen in a number of mental illnesses including schizophrenia, mood disorders and dementias of varying etiology. Studies in rodents suggest that acetylcholine (ACh) mediates attention, and cholinergic dysfunction is implicated in many cognitive neuropathologies. Questions arise, however, when one tries to model the cholinergic system as the basis for spatially precise attentional effects such as have been demonstrated in humans and non-human primates (NHPs). Specifically, the smallest piece of tissue which can be independently modulated by ACh may be too large to allow for the topographically precise enhancement of processing which appears to underlie attention in primates. Thus, while rodent studies have contributed much to our understanding of cholinergic processes, investigating cholinergic function in a species in which attention and arousal are more separable in behavioral tasks is essential. Also necessary, if we are to build the detailed mechanistic descriptions necessary to drive innovation in clinical practice, is a thorough understanding of cholinergic action in cortical circuits. Currently, our progress is hampered by a striking lack of circuit-level data regarding the structure and function of the cholinergic system and by a limited understanding of the behavioral drivers of ACh release. The work I propose to conduct during the mentored and independent phases of this award will address these gaps by 1) using anatomical techniques to provide quantitative data on ACh receptor localization in cortical areas modulated by attention (both phases), 2) using optogenetic techniques to examine the effect that naturalistic ACh release has on the processing of sensory input by a local cortical circuit in vivo (mentored phase), and 3) using high-resolution chemical sensing to determine the spatial profile of ACh release in the sensory cortex of a) the anesthetized rodent under optogenetic control (mentored phase) and b) the awake, behaving NHP during an attention task (both phases). To achieve these aims I need further training that will complement my existing skills in anatomy, physiology and pharmacology. Specifically, I need to learn how to train and record from NHPs that are engaged in tasks which probe attentional function. I also need a protected and innovative environment to work in while I develop protocols for chemical sensing in vivo in the behaving NHP. The Salk Institute is the ideal training environment for the achievement of these goals. Dr. John Reynolds, my mentor, is one of the world's foremost experts on the physiology of attention in NHPs and has a vibrant lab in which innovation is a normal part of the approach to research. The Salk Institute is also renowned for a collaborative atmosphere that fosters innovative approaches in the biological sciences. After a short period in this exciting environment, I expect to be ready to embark upon an independent research career and will seek a tenure-track position in Neuroscience.

摘要