Neural Pathways for Conditioned Stimuli in Eyeblink Conditioning

描述(由申请人提供)：建议项目的主要目标是提供关于小脑学习所必需的感觉输入路径的更详细的信息。我们首先将重点放在眨眼条件反射的听觉和视觉刺激通路上。Pi的实验室最近发现，丘脑内侧听核(内侧膝状核、板内后核和膝上核的内侧分支)是大鼠听性眨眼条件反射所必需的。内侧听觉丘脑是巴甫洛夫恐惧条件反射和音调线索回避条件反射中听觉条件刺激通路的一部分。具体目的1是通过识别这些核团的传入和传出听觉投射，进一步研究内侧听觉丘脑在啮齿类动物眨眼条件反射中的作用。这些核团是利用病变、神经束追踪、微刺激、单位记录和药物失活来实现眨眼条件反射所必需的。具体目的2是研究下丘及其与内侧听丘脑的联系在眨眼条件反射中的作用。具体目标3是对眨眼条件作用所必需的视觉CS通路进行初步研究。拟议的研究结果将提供关于小脑学习所必需的听觉和视觉CS通路的更完整的信息。这些发现还将对眨眼条件反射的发育分析产生重大影响，这些分析已经发现了小脑听觉CS输入的发育变化的证据。对各种发育障碍和精神分裂症的小脑功能的翻译研究也将受益于从拟议项目中获得的信息。更好地了解学习所必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患者的感觉-运动相互作用异常，如胎儿酒精综合征、自闭症和唐氏综合症。这项转化研究的总体目标是更好地了解导致发育障碍和精神分裂症的大脑异常，以便建立更有效的治疗方法。

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.