Neural Mechanisms of Visual and Auditory Stimulus Selection

描述：了解影响注意力的细胞机制对于开发有效治疗许多影响注意力的精神疾病和学习障碍至关重要。我们在仓鸮身上开发了实验方案，使我们能够研究注意力基本组成部分的细胞基础，刺激选择，定量细节。本研究的目的是分析自底向上（自动）和自顶向下神经元水平的刺激选择特征，并阐明这些过程背后的机制。自底向上和自顶向下的刺激选择的特性将在视觉顶盖中进行研究，这是一种已知与空间注意力有关的结构。多个同时的感觉刺激对神经元反应的影响将被测量，因为竞争刺激的显著性和位置是参数变化的。自上而下的信号（起源于前脑）偏向刺激选择将被电微刺激激活。最后，通过电生理和药理学灭活实验，探讨胆碱能核和gaba能核在自下而上和自上而下刺激选择中的作用。大脑选择刺激引起注意的机制尚不清楚。此外，胆碱能输入对大脑信息处理的影响尚不清楚。许多使人衰弱的疾病（如精神分裂症、自闭症、多动症）包括刺激选择功能障碍，而其他疾病（如阿尔茨海默病、帕金森病、唐氏病）则与胆碱能传递失调有关。了解刺激选择的细胞机制和胆碱能回路的功能对于开发能够减轻或补救这些疾病的破坏性影响的治疗方法至关重要。许多使人衰弱的精神疾病（如精神分裂症、自闭症和注意力障碍）包括注意力功能障碍，而其他疾病（如阿尔茨海默氏症、帕金森氏症和唐氏综合症）与大脑胆碱能回路失调有关。本研究将探讨注意力的细胞机制和胆碱能回路的功能特性。这项研究的结果将提供重要的信息，可能有助于开发治疗方法，减轻或纠正这些精神疾病的破坏性影响。

DESCRIPTION: Understanding the cellular mechanisms that underlie attention is crucial for developing effective treatments for the many psychiatric and learning disorders that affect attention. We have developed experimental protocols in the barn owl that allow us to study the cellular basis of a fundamental component of attention, stimulus selection, in quantitative detail. The aim of the proposed research is to analyze characteristics of bottom-up (automatic) and top-down stimulus selection at the neuronal level and to elucidate mechanisms that underlie these processes. The properties of bottom-up and top-down stimulus selection will be studied in the optic tectum, a structure known to be involved in spatial attention. The effects of multiple, simultaneous sensory stimuli on neuronal responses will be measured as the salience and location of competing stimuli are varied parametrically. Top-down signals (originating in the forebrain) that bias stimulus selection will be activated by electrical microstimulation. Finally, the respective roles of specialized cholinergic and GABAergic nuclei in bottom-up and top-down stimulus selection will be explored with electrophysiology and pharmacological inactivation experiments. The mechanisms by which the brain selects stimuli for attention are not known. In addition, the effects of cholinergic input on information processing in the brain are not understood. Many debilitating conditions (e.g., Schizophrenia, Autism, ADHD) include dysfunctions of stimulus selection, and others (e.g., Alzheimer's, Parkinson's, Down's) are associated with dysregulation of cholinergic transmission. An understanding of the cellular mechanisms of stimulus selection and the function of cholinergic circuits is crucial for developing treatments that can mitigate or remediate the devastating effects of these conditions. PUBLIC HEALTH RELEVANCE Many debilitating, psychiatric conditions (such as Schizophrenia, Autism and Attention Disorder) include dysfunctions of attention, and others (such as Alzheimer's, Parkinson's and Down's Syndrome) are associated with dysregulation of cholinergic circuitry in the brain. The proposed research will explore the cellular mechanisms of attention and the functional properties of cholinergic circuits. The results from this research will provide crucial information that may help in the development of treatments that can mitigate or remediate the devastating effects of these psychiatric conditions.