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

ABSTRACT

We question the widely accepted assumption that a molecular mechanism for long-term expression of synaptic plasticity is sufficient to explain the persistence of memories. Instead, we show that learning and memory require that 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 simulations of cerebellar-mediated eyelid conditioning, we examine the ability of three forms of plasticity at mossy fiber synapses in the cerebellar nucleus to contribute to learning and memory storage. Results suggest that when the simulation is exposed to reasonable patterns of "background" cerebellar activity, only one of these three rules allows for the retention of memories. When plasticity at the mossy fiber synapse is controlled by nucleus or climbing fiber activity, the circuit is unable to retain memories because of interactions within the network that produce spontaneous drift of synaptic strength. In contrast, a plasticity rule controlled by the activity of the Purkinje cell allows for a memory trace that is resistant to ongoing activity in the circuit. These results suggest specific constraints for theories of cerebellar motor learning and have general implications regarding the mechanisms that may contribute to the persistence of memories.