Delayed Complex Spike Response Evoked by Conditioned Stimulus Encodes Movement Onset Time and Is Determined by Intrinsic Inferior Olive Properties

Abstract

Recent studies demonstrate that after classical conditioning the conditioned stimulus (CS) triggers a delayed complex spike. This new finding revolutionizes our view on the role of complex spike activity. The classical view of the complex spike as an error signal has been replaced by a signal that encodes for expectation, prediction and reward. In this brief perspective, we review some of these works, focusing on the characteristic delay of the response (~80 ms), its independence on the time interval between CS and the unconditioned stimulus (US) and its relationship to movement onset. In view of these points, we suggest that the generation of complex spike activity following learning, encodes for timing of movements onset. We then provide original data recorded from Purkinje and cerebellar nuclei neurons, demonstrating that delayed complex spike activity is an intrinsic property of the cerebellar circuit. We, therefore, suggest that learning of classical conditioning involves modulation of cerebellar circuitry where timing is provided by the inferior olive and the movement kinematic is delivered by the cerebellar nuclei projection neurons.

Designing AAV Vectors for Monitoring the Subtle Calcium Fluctuations of Inferior Olive Network in vivo

“…With this insight, the distribution of calcium event rise times in-vivo translates to spike widths of 13.7 ± 0.7 ms with some spikes as long as 21.8 ms. Assuming a frequency of 270 Hz for the IO axon burst-firing (Mathy et al, 2009 ), such spikes could be expected to contain 4-5 “spikelets.” While the calcium recording from IO axons (CFs) were performed using the AAV-PHP.eB-Htr5b construct that likely can not report on the full range of IO spike dynamics, the CF events were similar ( Figure 12C2 ), providing further support to the notion that intrinsic IO dynamics can influence the shape of cerebellar CFs (Yarden-Rabinowitz and Yarom, 2019 ).…”