The Rhythmic Dance of the Cerebellar Purkinje Cell in Conditioning

Published on March 6, 2023

Imagine a skilled dancer learning to perform a perfectly timed routine. In the world of the brain, the cerebellar Purkinje cell is like the star dancer controlling eyeblinks, mastering the art of classical conditioning. While most models focus on how upstream networks influence timing, fascinating research demonstrates that directly stimulating the Purkinje cell can still lead to precise timing of eyeblinks. This challenges traditional thinking and sparks alternative approaches to understanding neural function. To shed light on this mystery, scientists have developed a groundbreaking computational model of time perception within the Purkinje cell itself. This model elegantly captures the intricate firing patterns of Purkinje cells during classical conditioning and offers unique insights into the passage-of-time phenomenon. Moreover, this model remains unaffected by the structure of external stimuli, adding another layer of complexity to our understanding. With its ability to make testable predictions through electrophysiological experiments, this study opens up new avenues for exploring how our brains master the art of timing.

The cerebellar Purkinje cell controlling eyeblinks can learn, remember, and reproduce the interstimulus interval in a classical conditioning paradigm. Given temporally separated inputs, the cerebellar Purkinje cell learns to pause its tonic inhibition of a motor pathway with high temporal precision so that an overt blink occurs at the right time. Most models place the passage-of-time representation in upstream network effects. Yet, bypassing the upstream network and directly stimulating the Purkinje cell’s pre-synaptic fibers during conditioning still causes acquisition of a well-timed response. Additionally, while network models are sensitive to variance in the temporal structure of probe stimulation, in vivo findings suggest that the acquired Purkinje cell response is not. Such findings motivate alternative approaches to modeling neural function. Here, we present a proof-of-principle model of the passage-of-time which is internal to the Purkinje cell and is invariant to probe structure. The model is consistent with puzzling findings, accurately recapitulates Purkinje cell firing during classical conditioning and makes testable electrophysiological predictions.1

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