Neural Pathways for Conditioned Stimuli in Eyeblink Conditioning

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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.