BackgroundThe oculomotor integrator (OI) in the vertebrate hindbrain transforms eye velocity input into persistent position coding output, which plays a crucial role in retinal image stability. For a mechanistic understanding of the integrator function and eye position control, knowledge about the tuning of the OI and other oculomotor nuclei is needed. Zebrafish are increasingly used to study integrator function and sensorimotor circuits, yet the precise neuronal tuning to motor variables remains uncharacterized.ResultsHere, we recorded cellular calcium signals while evoking monocular and binocular optokinetic eye movements at different slow-phase eye velocities. Our analysis reveals the anatomical distributions of motoneurons and internuclear neurons in the nucleus abducens as well as those of oculomotor neurons in caudally adjacent hindbrain volumes. Each neuron is tuned to eye position and/or velocity to variable extents and is only activated after surpassing particular eye position and velocity thresholds. While the abducens (rhombomeres 5/6) mainly codes for eye position, in rhombomeres 7/8, a velocity-to-position coding gradient exists along the rostro-caudal axis, which likely corresponds to the oculomotor structures storing velocity and position, and is in agreement with a feedforward mechanism of persistent activity generation. Position encoding neurons are recruited at eye position thresholds distributed across the behaviourally relevant dynamic range, while velocity-encoding neurons have more centred firing thresholds for velocity. In the abducens, neurons coding exclusively for one eye intermingle with neurons coding for both eyes. Many of these binocular neurons are preferentially active during conjugate eye movements and less active during monocular eye movements. This differential recruitment during monocular versus conjugate tasks represents a functional diversification in the final common motor pathway.ConclusionsWe localized and functionally characterized the repertoire of oculomotor neurons in the zebrafish hindbrain. Our findings provide evidence for a mixed but task-specific binocular code and suggest that generation of persistent activity is organized along the rostro-caudal axis in the hindbrain.

Saccades are rapid eye movements that redirect gaze. Their magnitudes and directions are tightly controlled by the oculomotor system, which is capable of generating conjugate, monocular, convergent and divergent saccades. Recent studies suggest a mainly monocular control of saccades in mammals, although the development of binocular control and the interaction of different functional populations is less well understood. For zebrafish, a well-established model in sensorimotor research, the nature of binocular control in this key oculomotor behavior is unknown. Here, we use the optokinetic response and calcium imaging to characterize how the developing zebrafish oculomotor system encodes the diverse repertoire of saccades. We find that neurons with phasic saccade-associated activity (putative burst neurons) are most frequent in dorsal regions of the hindbrain and show elements of both monocular and binocular encoding, revealing a mix of the response types originally hypothesized by Helmholtz and Hering. Additionally, we observed a certain degree of behavior-specific recruitment in individual neurons. Surprisingly, calcium activity is only weakly tuned to saccade size. Instead, saccade size is apparently controlled by a push–pull mechanism of opposing burst neuron populations. Our study reveals the basic layout of a developing vertebrate saccade system and provides a perspective into the evolution of the oculomotor system.

24Background: 25 The oculomotor integrator (OI) in the vertebrate hindbrain transforms eye velocity input into 26 persistent position coding output, which plays a crucial role in retinal image stability. For a 27 mechanistic understanding of the integrator function and eye position control, knowledge 28 about the tuning of the OI and other oculomotor nuclei is needed. Zebrafish are increasingly 29 used to study integrator function and sensorimotor circuits, yet the precise neuronal tuning 30 to motor variables remains uncharacterized. 31 32 Results: 33 Here, we recorded cellular calcium signals while evoking monocular and binocular optokinetic 34 eye movements at different slow-phase eye velocities. Our analysis reveals the anatomical 35 distributions of motoneurons and internuclear neurons in the nucleus abducens as well as 36 those of oculomotor neurons in caudally adjacent hindbrain volumes. Each neuron is tuned 37 to eye position and/or velocity to variable extents and is only activated after surpassing 38 particular eye position and velocity thresholds. While the abducens (rhombomeres 5/6) 39 mainly codes for eye position, in rhombomeres 7/8 a velocity-to-position coding gradient 40 exists along the rostro-caudal axis, which likely corresponds to the velocity and position 41 storage mechanisms. Position encoding neurons are recruited at eye position thresholds 42 distributed across the behavioral dynamic range, while velocity encoding neurons have more 43 centered firing thresholds for velocity. In the abducens, neurons coding exclusively for one 44 eye intermingle with neurons coding for both eyes. Many of these binocular neurons are 45 preferentially active during conjugate eye movements, which represents a functional 46 diversification in the final common motor pathway. 47 3Conclusions: 48 We localized and functionally characterized the repertoire of oculomotor neurons in the 49 zebrafish hindbrain. Our findings provide evidence for a mixed but task-specific binocular 50 code and suggest that generation of persistent activity is organized along the rostro-caudal 51 axis in the hindbrain.The oculomotor system is responsible for moving the eyes in vertebrates and is highly 71 conserved across species. Zebrafish are increasingly used to improve our understanding of 72 the oculomotor population code and eye movement control [1]- [6]. 73 The oculomotor system for horizontal eye movements consists of multiple elements (Fig. 1a). 74 It is responsible for generating and maintaining stable eye positions as well as eye movements 75 during saccades, optokinetic and vestibulo-ocular reflexes (OKR, VOR), and other behaviours. 76 The lateral and medial rectus (LR, MR), which represent the extraocular eye muscles 77 responsible for horizontal eye movements, are controlled by motoneurons (MN) in the 78 nucleus abducens (ABN) and the oculomotor nucleus (OMN), respectively. The OMN MNs are 79 activated by internuclear neurons (INN) residing in the contralateral ABN. The ABN receives 80 input from...