Simulations of cerebellar motor learning: Computational analysis of plasticity at the mossy fiber to deep nucleus synapse

We question the widely accepted assumption that a molecular mechanism for l ong-term expression of synaptic plasticity is sufficient to explain the per sistence of memories. Instead, we show that learning and memory require tha t these cellular mechanisms be correctly integrated within the architecture of the neural circuit. To illustrate this general conclusion, our studies are based on the well characterized synaptic organization of the cerebellum and its relationship to a simple form of motor learning. Using computer si mulations of cerebellar-mediated eyelid conditioning, we examine the abilit y of three forms of plasticity at mossy fiber synapses in the cerebellar nu cleus to contribute to learning and memory storage. Results suggest that wh en the simulation is exposed to reasonable patterns of "background" cerebel lar activity, only one of these three rules allows for the retention of mem ories. When plasticity at the mossy fiber synapse is controlled by nucleus or climbing fiber activity, the circuit is unable to retain memories becaus e of interactions within the network that produce spontaneous drift of syna ptic strength. In contrast, a plasticity rule controlled by the activity of the Purkinje cell allows for a memory trace that is resistant to ongoing a ctivity in the circuit. These results suggest specific constraints for theo ries of cerebellar motor learning and have general implications regarding t he mechanisms that may contribute to the persistence of memories.