The long-term objective of this project is to use Pavlovian eyelid conditioning as a tool to identify and thoroughly characterize mechanisms that operate in the cerebellum to mediate motor learning. The studies that are proposed extend ongoing efforts using reversible lesions of the cerebellum to identify sites and rules of plasticity that are responsible for cerebellar-mediated learning, and to identify the relative contributions of the cerebellar cortex and cerebellar nuclei.
The specific aims emphasize, in part, the mechanisms of plasticity in the cerebellar nuclei, to compliment the already well-characterized plasticity in the cerebellar cortex. A second emphasis will be to characterize how the relative contributions of the cerebellar cortex and nucleus change over acquisition, extinction, and reacquisition of learned responses. These studies will extend preliminary observations suggesting that 1) plasticity in both the cerebellar cortex and cerebellar nucleus is required for the expression of conditioned responses, 2) plasticity develops faster in the cerebellar cortex (during both acquisition and extinction training), and that 3) this leads to differential distributions of plasticity that can then explain such phenomena as savings, the faster rate of learning seen with reacquisition of responses following extinction than with original acquisition. The completion of these studies will provide a relatively clear picture of the basic mechanisms that operate in the cerebellum during learning and adaptation of movements. This should have important future implications for those afflicted with cerebellar damage or degenerative pathologies. In addition, mounting evidence suggests that certain parts of the human cerebellum are involved in non-motor, cognitive process. Since the synaptic organization of these regions and those involved in motor learning do not appear to differ, the cerebellum must contribute the same information processing to both motor and cognitive tasks. The proposed studies therefore represent the ability to study information processing of the cerebellum using quite tractable motor behaviors and then to apply that information to more complex cognitive processes. Thus, these studies will provide a basic understanding of information processing for important aspects of the motor system, and could provide the foundation for a deeper understanding of the neural basis of information processing that is applied to cognitive properties as well.
| Halverson, Hunter E; Khilkevich, Andrei; Mauk, Michael D (2018) Cerebellar Processing Common to Delay and Trace Eyelid Conditioning. J Neurosci 38:7221-7236 |
| Khilkevich, Andrei; Zambrano, Juan; Richards, Molly-Marie et al. (2018) Cerebellar implementation of movement sequences through feedback. Elife 7: |
| Khilkevich, Andrei; Canton-Josh, Jose; DeLord, Evan et al. (2018) A cerebellar adaptation to uncertain inputs. Sci Adv 4:eaap9660 |
| Hoffmann, Loren C; Zara, S James; DeLord, Evan D et al. (2018) Medial Auditory Thalamus Is Necessary for Expression of Auditory Trace Eyelid Conditioning. J Neurosci 38:8831-8844 |
| Hausknecht, Matthew; Li, Wen-Ke; Mauk, Michael et al. (2017) Machine Learning Capabilities of a Simulated Cerebellum. IEEE Trans Neural Netw Learn Syst 28:510-522 |
| Khilkevich, Andrei; Halverson, Hunter E; Canton-Josh, Jose Ernesto et al. (2016) Links Between Single-Trial Changes and Learning Rate in Eyelid Conditioning. Cerebellum 15:112-21 |
| 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 |
| Siegel, Jennifer J (2014) Modification of persistent responses in medial prefrontal cortex during learning in trace eyeblink conditioning. J Neurophysiol 112:2123-37 |
| Moya, Maria V; Siegel, Jennifer J; McCord, Eedann D et al. (2014) Species-specific differences in the medial prefrontal projections to the pons between rat and rabbit. J Comp Neurol 522:3052-74 |
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