Ramp-to-Threshold Dynamics in a Hindbrain Population Controls the Timing of Spontaneous Saccades

Abstract

Highlights• Comprehensive analysis of cells involved in spontaneous saccades and fixations.• Novel neuronal class with pre-saccadic rising activity that is predictive of saccade timing.• Ablations in the pre-saccadic rise population lead to delayed saccades. • New model system for understanding ramp-to-threshold dynamics and decision making. AbstractThe spontaneous generation of saccades and fixations provides a simple model for understanding how internal brain dynamics are linked to behavior. We coupled calcium imaging with focal laser ablations in larval zebrafish to comprehensively map the activity patterns underlying the generation and control of this spontaneous behavior. We found a continuum of activity types ranging from cells that burst only during saccades, to cells that displayed tonic discharge during fixations, to neurons whose activity rose in advance of saccades by multiple seconds before falling to baseline after saccade completion. The activity of these pre-saccadic rise neurons was predictive of upcoming saccade time when analyzed under the general framework of ramp-to-threshold models. Ablations in regions where these neurons were densest led to the greatest delay in saccade initiation. The rate of rise in these neurons was variable across cells and fixations, with increased slope coupled to shorter rise times. These findings suggest that the novel class of pre-saccadic rise neurons presented here are involved in the timing of self-initiated saccadic movements.

Predicting modular functions and neural coding of behavior from a synaptic wiring diagram

“…Our proposal that the VPNI should be extended also to R4-6 is consistent with the previous observation that integrator function was not completely abolished by inactivation of R7/8 26 . There was one previous report of eye position signals in R4-6 neurons that are not abducens neurons 44 but anatomical evidence for their inclusion in the VPNI has been lacking.…”

“…To validate our claims regarding function, we performed calcium imaging throughout the hindbrain in a separate set of animals to generate a map of neurons with activity related to oculomotor behavior. Recordings were obtained while the animals performed spontaneous eye movements in the dark, with activity ranging from neurons that exhibited bursts during saccades to those with perfectly persistent firing during fixations 44 . The maps from 20 age-matched animals were combined by registering them to a reference atlas 45 .…”

“…We found that the first and second principal components had post-saccadic activity largely related to position and velocity sensitivity respectively (see Figure 3A in 44 ). We characterized each STA using a scalar index, called φ in 44 , created from that STA's projections onto the first two principal components and found that this index does a good job of characterizing the average position and velocity-related activity seen across the population (see Figure 3C in 44 for a map of φ values and population average STAs). Position and velocity neurons were defined as neurons with an STA whose φ value of was within a specific range (-83 to 37 and 38-68 respectively).…”

“…Additionally, non-DO cells were required to have a saccade-triggered average with at least one significant time point (p<0.01 by an ANOVA test using Holm-Bonferroni correction) as defined in ref 44 and to have a ∆F F (which is defined as F −mean(F ) mean(F ) ), fluorescence response that was loosely related to eye position (R 2 greater than 0.2 when we run the above model replacing r with ∆F F ). The eye position sensitivity for fluorescence data was then scaled to average physiological VPNI responses from goldfish 48;89 .…”

“…Projections from the DO population were taken to be inhibitory while all other connections were taken to be excitatory (supplementary information). The remaining neurons in the oculomotor module were included as part of the VPNI--we did not consider other vestibular populations since only DO neurons in modO received vestibular afferents from the Viiith nerve; saccadic burst neurons are likely located in R2/3 44 , outside of our reconstructed volume; and recently discovered pre-saccadic ramp neurons 44 , are quite sparse in comparison to neurons with position signal.…”