While watching the Wimbledon final, have you ever wondered how your favorite tennis player can return a 200 km/h serve? Our latest paper ( https://www.cell.com/cell-reports/fulltext/S2211-1247(20)31526-6) provides clues about how the cerebellum may be a key player in winning the Grand Slam. Thread 👇 1/15
Returning serve illustrates the brain's incredible ability to near-instantaneously transform multimodal sensory inputs into a perfectly timed movement. As soon as the player hears and sees the serve, he/she jumps in the right direction and executes a precise motor program. 2/15
Patients with cerebellar pathology demonstrate that the cerebellum is crucial for facilitating such fine motor coordination (Holmes 1917; Ivry et al. 1988). Yet, how it orchestrates precisely timed motor responses to multimodal sensory inputs is not fully understood. 3/15
To tackle this problem, we developed a novel multisensory association task where mice report the co-occurrence of two different sensory stimuli (auditory and somatosensory) by initiating a timed motor response. 4/15
We observed that as mice learned to perform this task, their movements also became more precise. 5/15
Using a combination of optogenetics, Neuropixels and two-photon imaging we could then unpack how Purkinje cells are involved in guiding rapid sensorimotor transformations. 6/15
Optogenetic perturbation of Purkinje cells delays or entirely abolishes motor responses to multisensory stimuli. This suggests that Purkinje cells do, in fact, play a causal role in processing such rapid sensorimotor transformations. 7/15
To understand how exactly the cerebellum carries out this function, we used Neuropixels to simultaneously record from many Purkinje cells during our task. This revealed that the simple spike modulation by sensory stimuli correlated with the timing of motor initiation. 8/15
Given the well-established role of complex spike synchrony in motor timing, we next used two-photon calcium imaging of Purkinje cell dendrites to measure complex spike signals during our task. 9/15
We found that complex spike synchrony was topographically organized into parasagittal zones, the structure of which was highly conserved across animals: forming a consistent “complex spike map”. 10/15
Next, we wondered whether there is a relationship between complex spike synchrony and sensory-driven motor action. Indeed, we observed that higher levels of CS synchrony were correlated with more accurate movements and increased probability of motor initiation. 11/15
Finally, given that motor responses became increasingly accurate with learning, we asked whether complex spike synchrony developed in parallel with animal performance. Animals did, in fact, increase their level of complex spike synchrony across learning. 12/15
These findings help reconcile the view that climbing fibers are involved in sensory processing (Bower) with their role in orchestrating precisely timed movement (Llinas, Welsh, etc). 13/15
Upshot: simple spikes modulate the latency of motor initiation, and complex spikes refine its temporal precision (cf. ten Brinke 2017; Brown & Raman 2018). In other words, simple spikes allow you to return the ball at the right time, and complex spikes to do it precisely. 14/15
This work was a great team effort spearheaded by Shinichiro Tsutsumi together with @OscarChadney, @TinLong_Yiu, @BaumlerNeuro, Lavinia Faraggiana and @maxime_beau with support from the @wellcometrust, @ERC_Research and a steady supply of pastries from Miel Bakery. 15/15
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