Synchronous spiking of cerebellar Purkinje cells during control of movements

Abstract

SignificanceThe information that one region of the brain transmits to another is usually viewed through the lens of firing rates. However, if the output neurons could vary the timing of their spikes, then, through synchronization, they would spotlight information that may be critical for control of behavior. Here we report that, in the cerebellum, Purkinje cell populations that share a preference for error convey, to the nucleus, when to decelerate the movement, by reducing their firing rates and temporally synchronizing the remaining spikes.

Keywords: Purkinje cells; cerebellum; movement; saccades; synchrony.

Fig. 1.

P cells synchronized their SSs during saccades. (A) Experimental paradigm. Marmosets were trained to make saccades to visual targets that appeared randomly at one of eight directions. Onset of the primary saccade (labeled 1 in the lowest trace) resulted in the replacement of the primary target with a secondary target, also at a random direction. Following the secondary saccade (labeled 2), and a fixation period, reward was delivered, and the center target was displayed, resulting in a centripetal saccade (labeled 3). (B) Eye position for the primary (blue) and secondary (red) saccades in a typical experiment. (C) We used the MRI and CT images of each animal to guide the electrodes to lobule VI or VII of the cerebellar vermis. (D and E) SCs (blue) and CSs (red) in two simultaneously recorded P cells during saccades to various directions. Eye velocity is shown in yellow. The CSs are also aligned to the onset of the visual target. Both cells exhibited a reduction in SSs during saccades, with a modulation pattern that lasted much longer than the saccade. CS probability during the 200 ms following target onset is quantified via the center subplot. Baseline CS probability is shown by the brown circle. The target direction that produced the highest CS probability (CS-on) is estimated by the red line. (F) Synchronization index during saccades to various directions. This index quantified the probability of synchronization with respect to chance at 1-ms time bins. Eye velocity is indicated by the black curve. Probability of synchronization is greatest for saccades in direction CS+180, reaching a peak at around saccade deceleration.

Fig. 2.

CSs were tuned with respect to the direction of the target, and this tuning was anatomically organized. (A) CS response aligned to target onset. For each target type, the direction of stimulus that produced the greatest probability of CS was labeled as CS-on. Eye velocity is shown in gray. (B) CS response aligned to saccade onset. Modulation of CS response was present before saccades that were visually instructed. The response was muted before other saccades. (C) Within-cell difference between CS-on directions as computed following the onset of the primary target, the secondary target, and the central target. We found no systematic differences in the estimate of CS-on between various types of targets, and thus combined the response for all targets to compute the CS-on of each P cell. (D) Distribution of CS-on across the population of P cells. (E) CS tuning function. (F) Distribution of directions of CS-on in various regions of the vermis in two animals. Error bars are SEM.

Fig. 3.

Population response of SSs encoded saccade direction, peak velocity, and the onset of deceleration. (A) Average change in the firing rates of four representative P cells with respect to baseline, during saccades (data collapsed across all directions). (B) Clustering of saccade-aligned change in firing rates for all P cells, using the algorithm UMAP (70). Separating the data into two clusters produces bursters (red) and pausers (blue). (C) Activities of the bursters and pausers during saccade in various directions. The population response is the sum of firing rates in all P cells. Top: Activities of the bursters and pausers during saccades in various directions. Bottom: The population response, i.e., the sum of the firing rate in all P cells. (D) Population response aligned to saccade onset and deceleration onset. The burst tends to grow with saccade velocity and shifts forward in time, but the pause remains invariant with respect to the onset of deceleration. (E) Quantification of the population response with respect to saccade kinematics. (F) Magnitude of the burst before saccade onset as a function of saccade peak velocity in various directions. (G) Timing of the burst with respect to saccade onset decreased with increased velocity. However, despite a sevenfold change in peak velocity, the timing of the pause with respect to deceleration onset remained invariant.

Fig. 4.

P cells synchronized their spikes during saccade deceleration. (A) Probability of spike synchronization in pairs of P cells during the entire recording (41 ± 2 min, mean ± SEM). (Top) Probability of SS in P cell 2 at time point t (with respect to chance), given that an SS occurred in P cell 1 at time 0. (Middle) Probability of SS in P cell 2, given that a CS was produced in P cell 1 at time 0. (Bottom) Probability of CS in P cell 2 given that a CS was produced in P cell 1 at time 0. Bin is 1 ms. (B) Difference in CS-on directions among pairs of simultaneously recorded P cells. (C) Synchronization index (green) and firing rates (brown) for targeted saccades and other saccades. In the first and second rows, data are aligned to deceleration onset. In the third and fourth rows, data are aligned to saccade end. Firing rate is the population response. Bin size is 1 ms. (D) SS synchronization index during saccades (peak value) as a function of direction. (E) (Left) SS synchronization index during saccades (peak value) in direction CS+180, with respect to synchronization index as measured during nonsaccade periods. Dashed line is identity. (Right) Synchronization index during saccades with respect to CS synchronization index as measured during nonsaccade periods (1-ms bin for SS, and 10-ms bin for CS). Error bars are SEM.

Fig. 5.

Probability of synchronization increased with saccade velocity, and synchronization was more likely for saccades to targets. (A) For each animal and each type of saccade, we separated the movements based on their peak velocity and amplitude into high and low vigor. Error bars are SD. (B) High-vigor saccades exhibited a greater probability of SS synchrony than low-vigor saccades. Error bars are SEM. (C) A comparison of high-vigor saccades to targets vs. high-vigor other saccades. Amplitudes and velocities were larger for other saccades, yet saccades to targets were more likely to exhibit synchronization of SSs. Error bars are SEM.