Cerebellar mechanisms for motor learning: Testing predictions from a large-scale computer simulation

Javier Francisco Medina, The University of Texas Graduate School of Biomedical Sciences at Houston

Abstract

The cerebellum is the major brain structure that contributes to our ability to improve movements through learning and experience. We have combined computer simulations with behavioral and lesion studies to investigate how modification of synaptic strength at two different sites within the cerebellum contributes to a simple form of motor learning—Pavlovian conditioning of the eyelid response. These studies are based on the wealth of knowledge about the intrinsic circuitry and physiology of the cerebellum and the straightforward manner in which this circuitry is engaged during eyelid conditioning. Thus, our simulations are constrained by the well-characterized synaptic organization of the cerebellum and further, the activity of cerebellar inputs during simulated eyelid conditioning is based on existing recording data. These simulations have allowed us to make two important predictions regarding the mechanisms underlying cerebellar function, which we have tested and confirmed with behavioral studies. The first prediction describes the mechanisms by which one of the sites of synaptic modification, the granule to Purkinje cell synapses (gr [special characters omitted] Pkj) of the cerebellar cortex, could generate two time-dependent properties of eyelid conditioning—response timing and the ISI function. An empirical test of this prediction using small, electrolytic lesions of the cerebellar cortex revealed the pattern of results predicted by the simulations. The second prediction made by the simulations is that modification of synaptic strength at the other site of plasticity, the mossy fiber to deep nuclei synapses (mf [special characters omitted] nuc), is under the control of Purkinje cell activity. The analysis predicts that this property should confer mf [special characters omitted] nuc synapses with resistance to extinction. Thus, while extinction processes erase plasticity at the first site, residual plasticity at mf [special characters omitted] nuc synapses remains. The residual plasticity at the mf [special characters omitted] nuc site confers the cerebellum with the capability for rapid relearning long after the learned behavior has been extinguished. We confirmed this prediction using a lesion technique that reversibly disconnected the cerebellar cortex at various stages during extinction and reacquisition of eyelid responses. The results of these studies represent significant progress toward a complete understanding of how the cerebellum contributes to motor learning.

Subject Area

Neurology|Molecular biology

Recommended Citation

Medina, Javier Francisco, "Cerebellar mechanisms for motor learning: Testing predictions from a large-scale computer simulation" (2000). Texas Medical Center Dissertations (via ProQuest). AAI9964749.
https://digitalcommons.library.tmc.edu/dissertations/AAI9964749

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