Superior colliculus drives stimulus-evoked directionally biased saccades and attempted head movements in head-fixed mice

Animals investigate their environments by directing their gaze towards salient stimuli. In the prevailing view, mouse gaze shifts entail head rotations followed by brainstem-mediated eye movements, including saccades to reset the eyes. These 'recentering' saccades are attributed to head movement-related vestibular cues. However, microstimulating mouse superior colliculus (SC) elicits directed head and eye movements resembling SC-dependent sensory-guided gaze shifts in other species, suggesting that mouse gaze shifts may be more flexible than has been recognized. We investigated this possibility by tracking eye and attempted head movements in a head-fixed preparation that eliminates head movement-related sensory cues. We found tactile stimuli evoke directionally biased saccades coincident with attempted head rotations. Differences in saccade endpoints across stimuli are associated with distinct stimulus-dependent relationships between initial eye position and saccade direction and amplitude. Optogenetic perturbations revealed SC drives these gaze shifts. Thus, head-fixed mice make sensory-guided, SC-dependent gaze shifts involving coincident, directionally biased saccades and attempted head movements. Our findings uncover flexibility in mouse gaze shifts and provide a foundation for studying head-eye coupling.

The role of fixation disengagement and oculomotor preparation in gap saccade task is gap-duration dependent

The influence of internal brain state on behavioral performance is well illustrated by the gap-saccade task, in which saccades might be initiated with short latency (express saccade) or with long latency (regular saccade) even though the external visual condition is identical. Accumulated evidence has demonstrated that the internal brain state is different before the initiation of an express saccade than of a regular saccade. However, the reported origin of the fluctuation of internal brain state is disputed among previous studies, e.g., the fixation disengagement theory versus the oculomotor preparation theory. In the present study, we examined these two theories by analyzing the rate and direction of fixational saccades, i.e., small amplitude saccades during fixation period, because they could be modulated by internal brain state. Since fixation disengagement is not spatially tuned, it might affect the rate but not direction of fixational saccade. In contrast, oculomotor preparation can contain the spatial information for upcoming saccade, thus, it might have a distinct effect on fixational saccade direction. We found that the different spatiotemporal characteristics of fixational saccades among tasks with different gap durations reveals different driven force to change the internal brain state. Under short gap duration (100 ms), fixation disengagement plays a primary role in switching internal brain state. Conversely, under medium (200 ms) and long (400 ms) gap durations, oculomotor preparation plays a primary role. These results suggest that both fixation disengagement and oculomotor preparation can change the internal brain state, but their relative contributions are gap-duration dependent.

A corollary discharge mediates saccade related inhibition of single units in mnemonic structures of the human brain

Despite the critical link between visual exploration and memory, little is known about how single-unit activity (SUA) in the human mesial temporal lobe (MTL) is modulated by saccadic eye movements (SEMs). Here we characterize SEM associated SUA modulations, unit-by-unit, and contrast them to image onset, and to occipital lobe SUA. We reveal evidence for a corollary discharge (CD)-like modulatory signal that accompanies SEMs, inhibiting/exciting a unique population of broad/narrow spiking units, respectively, before and during SEMs, and with directional selectivity. These findings comport well with the timing, directional nature, and inhibitory circuit implementation of a CD. Additionally, by linking SUA to event-related potentials (ERPs), which are directionally modulated following SEMs, we recontextualize the ERP associated with SEM as a proxy for both the strength of inhibition and saccade direction, providing a mechanistic underpinning for the more commonly recorded SEM-related ERP in the human brain.

Spontaneous grouping of saccade timing in the presence of task-irrelevant objects

Sequential movements are often grouped into several chunks, as evidenced by the modulation of the timing of each elemental movement. Even during synchronized tapping with a metronome, we sometimes feel subjective accent for every few taps. To examine whether motor segmentation emerges during synchronized movements, we trained monkeys to generate a series of predictive saccades synchronized with visual stimuli which sequentially appeared for a fixed interval (400 or 600 ms) at six circularly arranged landmark locations. We found two types of motor segmentations that featured periodic modulation of saccade timing. First, the intersaccadic interval (ISI) depended on the target location and saccade direction, indicating that particular combinations of saccades were integrated into motor chunks. Second, when a task-irrelevant rectangular contour surrounding three landmarks ("inducer") was presented, the ISI significantly modulated depending on the relative target location to the inducer. All patterns of individual differences seen in monkeys were also observed in humans. Importantly, the effects of the inducer greatly decreased or disappeared when the animals were trained to generate only reactive saccades (latency >100 ms), indicating that the motor segmentation may depend on the internal rhythms. Thus, our results demonstrate two types of motor segmentation during synchronized movements: one is related to the hierarchical organization of sequential movements and the other is related to the spontaneous grouping of rhythmic events. This experimental paradigm can be used to investigate the underlying neural mechanism of temporal grouping during rhythm production.

Neural correlates of goal-directed and non–goal-directed movements

What are the cortical neural correlates that distinguish goal-directed and non–goal-directed movements? We investigated this question in the monkey frontal eye field (FEF), which is implicated in voluntary control of saccades. Here, we compared FEF activity associated with goal-directed (G) saccades and non–goal-directed (nG) saccades made by the monkey. Although the FEF neurons discharged before these nG saccades, there were three major differences in the neural activity: First, the variability in spike rate across trials decreased only for G saccades. Second, the local field potential beta-band power decreased during G saccades but did not change during nG saccades. Third, the time from saccade direction selection to the saccade onset was significantly longer for G saccades compared with nG saccades. Overall, our results reveal unexpected differences in neural signatures for G versus nG saccades in a brain area that has been implicated selectively in voluntary control. Taken together, these data add critical constraints to the way we think about saccade generation in the brain.

Functional links between sensory representations, choice activity, and sensorimotor associations in parietal cortex

Three-dimensional (3D) representations of the environment are often critical for selecting actions that achieve desired goals. The success of these goal-directed actions relies on 3D sensorimotor transformations that are experience-dependent. Here we investigated the relationships between the robustness of 3D visual representations, choice-related activity, and motor-related activity in parietal cortex. Macaque monkeys performed an eight-alternative 3D orientation discrimination task and a visually guided saccade task while we recorded from the caudal intraparietal area using laminar probes. We found that neurons with more robust 3D visual representations preferentially carried choice-related activity. Following the onset of choice-related activity, the robustness of the 3D representations further increased for those neurons. We additionally found that 3D orientation and saccade direction preferences aligned, particularly for neurons with choice-related activity, reflecting an experience-dependent sensorimotor association. These findings reveal previously unrecognized links between the fidelity of ecologically relevant object representations, choice-related activity, and motor-related activity.

Dynamic encoding of saccade sequences in primate frontal eye field

Frontal eye field (FEF) is a key part of oculomotor system, with dominant responses to the direction of single saccades. However, whether and how FEF contributes to sequential saccades remain largely unknown. Here by training rhesus monkeys to perform sequential saccades and recording the neuronal activities in FEF, we found that the sequence-related activities are clearly represented in FEF, and many neurons’ selectivity to saccade direction undergoes dynamic changes during sequential task. In addition, the sequence-related activities are context-dependent, with different firing activities during memory- versus visually-guided sequence. Supra-threshold microstimulation in FEF evokes saccade without altering the overall sequence structure. Pharmacological inactivation of FEF severely impaired the monkey’s performance of sequential saccades, with different effects on the same actions at different positions within the sequence. These results reveal the context-dependent dynamic encoding of saccade direction in FEF, and underscore a critical role of FEF in planning and execution of sequential saccades.In BriefJia, Puyang et al. employed in vivo recording to reveal the dynamic encoding of sequential saccades in primate frontal eye field (FEF), then used electric microstimulation and reversible inactivation to demonstrate the causal role of FEF in controlling saccade sequences.HighlightsFEF neurons respond differently during sequential vs. single saccadesSequence-related FEF activity is context-dependentFEF microstimulation induced saccade without altering sequence structureFEF inactivation severely impaired the performance of sequential saccades

Choice activity stabilizes sensory representations and mediates sensorimotor associations in parietal cortex

Selecting actions which achieve desired goals often requires three-dimensional (3D) representations of the environment. Because the sensory epithelia cannot directly encode the world’s 3D spatial features, sensory signals must be converted into 3D representations. Here we investigated the relationships between the quality of 3D visual representations, choice-related activity, and motor-related activity in the parietal cortex of macaque monkeys using an eight-alternative 3D orientation discrimination task, visually guided saccade task, and laminar probe recordings. We found that choice activity was preferentially carried by caudal intraparietal area neurons with more robust 3D representations. Choice activity further stabilized the 3D representations, rather than attenuating information not directly relevant to the behavioral task (nuisance variables). An experience-dependent, sensorimotor association additionally aligned sensory and saccade direction preferences, particularly for neurons with choice activity. These findings reveal novel roles for choice activity in improving the fidelity of ecologically relevant object representations and mediating sensorimotor associations.