Eyelid conditioning in rabbits is an unusually direct and experimentally tractable way to study learning and information processing of the cerebellum. Cerebellar patients experience debilitating motor impairments and damage of the lateral cerebellum contribute produces a variety of cognitive deficits. Understanding the internal operations of the cerebellum is therefore both important clinically, and important for the opportunity it provides to use an experimentally tractable system to the analysis of the neural basis of cognition. We propose to continue ongoing efforts that use eyelid conditioning to understand both what the cerebellum learning and computes and how its neurons and synapses accomplish underlie these capabilities. We will use high-density in vivo recordings of cerebellar neurons during the acquisition and execution of key behavioral properties of eyelid conditioning to test specific hypotheses derived from large-scale computer simulations of the cerebellum. We will use the ability to perform long-term recordings of cerebellar neurons to identify the sequence of events that occurs during learning of a new response and to quantify the relationships between cerebellar neurons and behavior. We will use lesions and in vivo recordings to examine how the contributions of cerebellar cortex to learning may vary depending on the timing of inputs to the cerebellum. These studies will help move our understanding of computation and learning in the cerebellum to a level not yet accomplished for any other system of the brain.
These experiments seek to understand the mechanisms of learning within the cerebellum. Understanding these mechanisms will help us understand how all systems of the brain support learning and memory. Such knowledge is the basis for the development of strategies to prevent and to treat the disorders of learning and memory that affect so many people.
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|Halverson, Hunter E; Hoffmann, Loren C; Kim, Yujin et al. (2016) Systematic variation of acquisition rate in delay eyelid conditioning. Behav Neurosci 130:553-62|
|Halverson, Hunter E; Khilkevich, Andrei; Mauk, Michael D (2015) Relating cerebellar purkinje cell activity to the timing and amplitude of conditioned eyelid responses. J Neurosci 35:7813-32|
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|Siegel, Jennifer J (2014) Modification of persistent responses in medial prefrontal cortex during learning in trace eyeblink conditioning. J Neurophysiol 112:2123-37|
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|Siegel, Jennifer J; Mauk, Michael D (2013) Persistent activity in prefrontal cortex during trace eyelid conditioning: dissociating responses that reflect cerebellar output from those that do not. J Neurosci 33:15272-84|
|Kalmbach, Brian E; Mauk, Michael D (2012) Multiple sites of extinction for a single learned response. J Neurophysiol 107:226-38|
|Kalmbach, Brian E; Voicu, Horatiu; Ohyama, Tatsuya et al. (2011) A subtraction mechanism of temporal coding in cerebellar cortex. J Neurosci 31:2025-34|
|Kalmbach, Brian E; Ohyama, Tatsuya; Mauk, Michael D (2010) Temporal patterns of inputs to cerebellum necessary and sufficient for trace eyelid conditioning. J Neurophysiol 104:627-40|
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