Modeling the role of cerebellar granule cells and interneurons in the timing and acquisition of conditioned responses
Radell, Milen L.
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The role of the cerebellar cortex in the acquisition and timing of conditioned responses remains unclear. Previous studies have failed to account for the possible impacts of the cerebellar molecular layer interneurons (the basket and stellate cells). The contributions of learning-related changes at the parallel fibers, long thought to be critical for timing, have also come into question. The current study uses computer simulations of the cerebellar cortex, including the molecular layer interneurons, to clarify their possible role. The simulations test the hypotheses that: (1) molecular layer inhibition influences timing precision; (2) the effects of inhibition depend on the site of learning-related changes (parallel fibers vs. ascending branch); (3) stellate and basket inhibition make a differential contribution; and (4) changes in inhibition can explain the changes in acquisition and timing of conditioned responses associated with autism. The current model replicates several features of empirical Purkinje cell conditioned responses, showing a correlation between onset, peak and offset latencies and US onset that is typically independent of CS duration. The simulations predict that whether molecular layer inhibition results in an enhancement of acquisition, or changes in timing (as in children with autism), depends on the type of inhibition (basket vs. stellate), the level of inhibition; and where learning-related changes occur (parallel vs. ascending branch synapses). The model also suggests that there is a trade-off between timing precision and the amplitude of the conditioned response with imbalances between stellate and basket inhibition leading to changes in timing and amplitude. In contrast, when basket and stellate inhibition were equal, irrespective of level, conditioned responses were similar and of moderate amplitude and precision. Overall, conditioned response amplitudes were lower when learning-related changes took place at the ascending instead of the parallel fiber connections, suggesting that the ascending branch synapses can only support a lower probability of responding.