Neural Pathways for Conditioned Stimuli in Eyeblink Conditioning

眨眼条件反射中条件刺激的神经通路

• 批准号: 7613423
• 负责人: John H Freeman
• 金额: $ 26.55万
• 依托单位: UNIVERSITY OF IOWA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7613423
• 关键词: Auditory; Autistic Disorder; Bilateral; Blinking; Brain; Cell Nucleus; Cerebellar Nuclei; Cerebellum; Cochlear nucleus; Conditioned Stimulus; Contralateral; Cues; Development; Down Syndrome; Eye; Fetal Alcohol Syndrome; Functional Imaging; Goals; Inferior Colliculus; Intralaminar Nuclear Group; Investigation; Laboratories; Lateral Geniculate Body; Learning; Lesion; Light; Medial; Motor; Muscimol; Nature; Neural Pathways; Neurobiology; Neurons; Nictitating Membrane; Oryctolagus cuniculus; Pathway interactions; Patients; Pontine structure; Rattus; Reporting; Research Personnel; Rodent; Role; Schizophrenia; Sensory; Series; Stimulus; Thalamic Nuclei; Thalamic structure; Translational Research; Visual; Visual Pathways; Work; auditory stimulus; conditioned fear; conditioning; design; developmental disease; effective therapy; microstimulation; mossy fiber; neural tract; prevent; programs; research study; superior colliculus Corpora quadrigemina; translational study; visual stimulus

DESCRIPTION (provided by applicant): The main goal of the proposed project is to provide more detailed information about the sensory input pathways that are necessary for cerebellar learning. We will initially focus on auditory and visual stimulus pathways in eyeblink conditioning. The PI's laboratory recently discovered that the medial auditory thalamic nuclei (medial division of the medial geniculate, posterior intralaminar nucleus, and suprageniculate nucleus) are necessary for auditory eyeblink conditioning in rats. The medial auditory thalamus is part of the auditory conditioned stimulus (CS) pathway in Pavlovian fear conditioning and tone-cued avoidance conditioning. Specific Aim 1 is to further examine the role of the medial auditory thalamus in rodent eyeblink conditioning by identifying the afferent and efferent auditory projections of these nuclei that are necessary for eyeblink conditioning using lesions, neural tract tracing, microstimulation, unit recording, and pharmacological inactivation. Specific Aim 2 is to examine the role of the inferior colliculus and its connections with the medial auditory thalamus in eyeblink conditioning. Specific Aim 3 is to conduct an initial investigation of the visual CS pathways that are necessary for eyeblink conditioning. The findings of the proposed studies will provide more complete information regarding the auditory and visual CS pathways that are necessary for cerebellar learning. The findings will also have significant implications for developmental analyses of eyeblink conditioning, which have found evidence for developmental changes in auditory CS input to the cerebellum. Translational studies of cerebellar function in various developmental disorders and schizophrenia will also benefit from information derived from the proposed project. A better understanding of the sensory inputs to the cerebellum that are necessary for learning will help guide functional imaging studies to better assess abnormalities in sensory-motor interactions in patients with schizophrenia and various developmental disorders such as fetal alcohol syndrome, autism, and Down syndrome. A general goal of the translational research is to better understand the brain abnormalities underlying developmental disorders and schizophrenia in order to establish more effective treatments.

描述（由申请人提供）：拟议项目的主要目标是提供有关小脑学习所需的感觉输入路径的更详细信息。我们首先将重点关注眨眼调节中的听觉和视觉刺激途径。 PI 实验室最近发现内侧听觉丘脑核（内侧膝状体的内侧部分、后层内核和膝上核）对于大鼠的听觉眨眼调节是必需的。内侧听觉丘脑是巴甫洛夫恐惧条件反射和音调回避条件反射中听觉条件刺激（CS）通路的一部分。具体目标 1 是通过识别这些核的传入和传出听觉投射来进一步检查内侧听觉丘脑在啮齿动物眨眼条件反射中的作用，这些听觉投射对于使用损伤、神经束追踪、微刺激、单位记录和药理学失活进行眨眼条件反射是必需的。具体目标 2 是检查下丘的作用及其与内侧听觉丘脑在眨眼调节中的联系。具体目标 3 是对眨眼条件反射所必需的视觉 CS 通路进行初步研究。拟议研究的结果将提供有关小脑学习所需的听觉和视觉 CS 通路的更完整信息。这些发现还将对眨眼条件反射的发育分析产生重大影响，该分析已经找到了小脑听觉 CS 输入发育变化的证据。各种发育障碍和精神分裂症中小脑功能的转化研究也将受益于拟议项目的信息。更好地了解学习所需的小脑感觉输入将有助于指导功能成像研究，以更好地评估精神分裂症和各种发育障碍（如胎儿酒精综合症、自闭症和唐氏综合症）患者感觉运动相互作用的异常情况。转化研究的总体目标是更好地了解发育障碍和精神分裂症背后的大脑异常，以便建立更有效的治疗方法。