Neural Pathways for Conditioned Stimuli in Eyeblink Conditioning

描述（由申请人提供）：拟建项目的主要目标是提供有关小脑学习所必需的感觉输入通路的更详细信息。我们将首先关注眨眼条件反射中的听觉和视觉刺激途径。PI的实验室最近发现，内侧丘脑听觉核（内侧膝状核、后板间核和扣上核的内侧分支）对大鼠的听觉眨眼条件反射是必需的。内侧听觉丘脑是巴甫洛夫恐惧条件反射和声调暗示回避条件反射中听觉条件刺激通路的一部分。具体目标1是通过使用损伤、神经束追踪、微刺激、单位记录和药物失活来识别这些核的传入和传出听觉投射，进一步研究内侧听觉丘脑在啮齿动物眨眼条件反射中的作用。具体目的2是研究下丘及其与内侧听觉丘脑的连接在眨眼条件反射中的作用。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。这些研究的结果将为小脑学习所必需的听觉和视觉CS通路提供更完整的信息。这一发现也将对眨眼条件反射的发育分析产生重大影响，该分析已经发现了小脑听觉CS输入的发育变化的证据。各种发育障碍和精神分裂症的小脑功能转化研究也将受益于拟议项目的信息。更好地了解学习所必需的小脑的感觉输入，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（如胎儿酒精综合征、自闭症和唐氏综合征）患者的感觉-运动相互作用异常。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。

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.