We recently developed a biomimetic robotic eye with six independent tendons, each controlled by their own rotatory motor, and with insertions on the eye ball that faithfully mimic the biomechanics of the human eye. We constructed an accurate physical computational model of this system, and learned to control its nonlinear dynamics by optimising a cost that penalised saccade inaccuracy, movement duration, and total energy expenditure of the motors. To speed up the calculations, the physical simulator was approximated by a recurrent neural network (NARX). We showed that the system can produce realistic eye movements that closely resemble human saccades in all directions: their nonlinear main-sequence dynamics (amplitude-peak eye velocity and duration relationships), cross-coupling of the horizontal and vertical movement components leading to approximately straight saccade trajectories, and the 3D kinematics that restrict 3D eye orientations to a plane (Listing\'s law). Interestingly, the control algorithm had organised the motors into appropriate agonist-antagonist muscle pairs, and the motor signals for the eye resembled the well-known pulse-step characteristics that have been reported for monkey motoneuronal activity. We here fully analyse the eye-movement properties produced by the computational model across the entire oculomotor range and the underlying control signals. We argue that our system may shed new light on the neural control signals and their couplings within the final neural pathways of the primate oculomotor system, and that an optimal control principle may account for a wide variety of oculomotor behaviours. The generated data are publicly available at https://data.ru.nl/collections/di/dcn/DSC_626870_0003_600.

Besides controlling eye movements, the brain\'s oculomotor system has been implicated in the control of covert spatial attention and the rehearsal of spatial information in working memory. We investigated whether the oculomotor system also contributes to rehearsing visual objects in working memory when object location is never asked about. To address this, we tracked the incidental use of locations for mnemonic rehearsal via directional biases in microsaccades while participants maintained two visual objects (colored oriented gratings) in working memory. By varying the stimulus configuration (horizontal, diagonal, and vertical) at encoding, we could quantify whether microsaccades were more aligned with the configurational axis of the memory contents, as opposed to the orthogonal axis. Experiment 1 revealed that microsaccades continued to be biased along the axis of the memory content several seconds into the working memory delay. In Experiment 2, we confirmed that this directional microsaccade bias was specific to memory demands, ruling out lingering effects from passive and attentive encoding of the same visual objects in the same configurations. Thus, by studying microsaccade directions, we uncover oculomotor-driven rehearsal of visual objects in working memory through their associated locations.

The evolution and development of the head have long captivated researchers due to the crucial role of the head as the gateway for sensory stimuli and the intricate structural complexity of the head. Although significant progress has been made in understanding head development in various vertebrate species, our knowledge of early human head ontogeny remains limited. Here, we used advanced whole-mount immunostaining and 3D imaging techniques to generate a comprehensive 3D cellular atlas of human head embryogenesis. We present detailed developmental series of diverse head tissues and cell types, including muscles, vasculature, cartilage, peripheral nerves, and exocrine glands. These datasets, accessible through a dedicated web interface, provide insights into human embryogenesis. We offer perspectives on the branching morphogenesis of human exocrine glands and unknown features of the development of neurovascular and skeletomuscular structures. These insights into human embryology have important implications for understanding craniofacial defects and neurological disorders and advancing diagnostic and therapeutic strategies.

Medial rectus motoneurons mediate nasally directed horizontal eye movements. These motoneurons receive two major excitatory inputs, from the abducens internuclear neurons (ABD Ints) and neurons of the lateral vestibular nucleus whose axons course through the ascending tract of Deiters (ATD). In the present work, we have recorded in the alert chronic cat preparation the discharge activity of these two premotor neurons simultaneously with eye movements, to discern their relative contribution to the firing pattern of medial rectus motoneurons. ABD Int discharge was accurately correlated with eye movements, displaying high sensitivities to eye position and eye velocity. ATD neurons also discharged in relation to spontaneous and vestibular eye movements but showed significantly lower eye position and eye velocity sensitivities. Outstandingly, ATD neurons presented a significantly lower eye position threshold for recruitment compared to both ABD Ints and medial rectus motoneurons. Therefore, ATD neurons exhibited eye position and velocity signals during spontaneous and vestibular eye movements, which were of lower magnitude than those of ABD Ints, but due to their low recruitment threshold, they could play a significant role in facilitating ABD Int signal transmission onto medial rectus motoneurons.

BDNF is a neurotrophin family member implicated in many different neuronal functions, from neuronal survival during development to synaptic plasticity associated with processes of learning and memory. Its presence in the oculomotor system has previously been demonstrated, as it regulates afferent composition of extraocular motoneurons and their firing pattern. Moreover, BDNF expression increases after extraocular motoneuron partial deafferentation, in parallel with terminal axon sprouting from the remaining axons. To elucidate whether BDNF could play an active role in this process, we performed partial deafferentation of the medial rectus motoneurons through transection of one of the two main afferents, that is, the ascending tract of Deiters, and injected BDNF into the motoneuron target muscle, the medial rectus. Furthermore, to check whether BDNF could stimulate axon sprouting without lesions, we performed the same experiment without any lesions. Axon terminal sprouting was assessed by calretinin immunostaining, which specifically labels the remaining afferent system on medial rectus motoneurons, the abducens internuclear neurons. The results presented herein show that exogenous BDNF stimulated terminal axon growth, allowing the total recovery of synaptic coverage around the motoneuron somata. Moreover, calretinin staining in the neuropil exceeded that present in the control situation. Thus, BDNF could also stimulate axonal sprouting in the neuropil of intact animals. These results point to an active role of BDNF in plastic adaptations that take place after partial deafferentation.

Amblyopia is the most common cause of vision loss in children and can persist into adulthood in the absence of effective intervention. Previous clinical and neuroimaging studies have suggested that the neural mechanisms underlying strabismic amblyopia and anisometropic amblyopia may be different. Therefore, we performed a systematic review of magnetic resonance imaging studies investigating brain alterations in patients with these two subtypes of amblyopia; this study is registered with PROSPERO (registration ID: CRD42022349191). We searched three online databases (PubMed, EMBASE, and Web of Science) from inception to April 1, 2022; 39 studies with 633 patients (324 patients with anisometropic amblyopia and 309 patients with strabismic amblyopia) and 580 healthy controls met the inclusion criteria (e.g., case-control designed, peer-reviewed articles) and were included in this review. These studies highlighted that both strabismic amblyopia and anisometropic amblyopia patients showed reduced activation and distorted topological cortical activated maps in the striate and extrastriate cortices during task-based functional magnetic resonance imaging with spatial-frequency stimulus and retinotopic representations, respectively; these may have arisen from abnormal visual experiences. Compensations for amblyopia that are reflected in enhanced spontaneous brain function have been reported in the early visual cortices in the resting state, as well as reduced functional connectivity in the dorsal pathway and structural connections in the ventral pathway in both anisometropic amblyopia and strabismic amblyopia patients. The shared dysfunction of anisometropic amblyopia and strabismic amblyopia patients, relative to controls, is also characterized by reduced spontaneous brain activity in the oculomotor cortex, mainly involving the frontal and parietal eye fields and the cerebellum; this may underlie the neural mechanisms of fixation instability and anomalous saccades in amblyopia. With regards to specific alterations of the two forms of amblyopia, anisometropic amblyopia patients suffer more microstructural impairments in the precortical pathway than strabismic amblyopia patients, as reflected by diffusion tensor imaging, and more significant dysfunction and structural loss in the ventral pathway. Strabismic amblyopia patients experience more attenuation of activation in the extrastriate cortex than in the striate cortex when compared to anisometropic amblyopia patients. Finally, brain structural magnetic resonance imaging alterations tend to be lateralized in the adult anisometropic amblyopia patients, and the patterns of brain alterations are more limited in amblyopic adults than in children. In conclusion, magnetic resonance imaging studies provide important insights into the brain alterations underlying the pathophysiology of amblyopia and demonstrate common and specific alterations in anisometropic amblyopia and strabismic amblyopia patients; these alterations may improve our understanding of the neural mechanisms underlying amblyopia.

Neuronal wiring diagrams reconstructed by electron microscopy1,2,3,4,5 pose new questions about the organization of nervous systems following the time-honored tradition of cross-species comparisons.6,7 The C. elegans connectome has been conceptualized as a sensorimotor circuit that is approximately feedforward,8,9,10,11 starting from sensory neurons proceeding to interneurons and ending with motor neurons. Overrepresentation of a 3-cell motif often known as the \"feedforward loop\" has provided further evidence for feedforwardness.10,12 Here, we contrast with another sensorimotor wiring diagram that was recently reconstructed from a larval zebrafish brainstem.13 We show that the 3-cycle, another 3-cell motif, is highly overrepresented in the oculomotor module of this wiring diagram. This is a first for any neuronal wiring diagram reconstructed by electron microscopy, whether invertebrate12,14 or mammalian.15,16,17 The 3-cycle of cells is \"aligned\" with a 3-cycle of neuronal groups in a stochastic block model (SBM)18 of the oculomotor module. However, the cellular cycles exhibit more specificity than can be explained by the group cycles-recurrence to the same neuron is surprisingly common. Cyclic structure could be relevant for theories of oculomotor function that depend on recurrent connectivity. The cyclic structure coexists with the classic vestibulo-ocular reflex arc for horizontal eye movements,19 and could be relevant for recurrent network models of temporal integration by the oculomotor system.20,21.

The potassium chloride cotransporter 2 (KCC2) is the main Cl- extruder in neurons. Any alteration in KCC2 levels leads to changes in Cl- homeostasis and, consequently, in the polarity and amplitude of inhibitory synaptic potentials mediated by GABA or glycine. Axotomy downregulates KCC2 in many different motoneurons and it is suspected that interruption of muscle-derived factors maintaining motoneuron KCC2 expression is in part responsible. In here, we demonstrate that KCC2 is expressed in all oculomotor nuclei of cat and rat, but while trochlear and oculomotor motoneurons downregulate KCC2 after axotomy, expression is unaltered in abducens motoneurons. Exogenous application of vascular endothelial growth factor (VEGF), a neurotrophic factor expressed in muscle, upregulated KCC2 in axotomized abducens motoneurons above control levels. In parallel, a physiological study using cats chronically implanted with electrodes for recording abducens motoneurons in awake animals, demonstrated that inhibitory inputs related to off-fixations and off-directed saccades in VEGF-treated axotomized abducens motoneurons were significantly higher than in control, but eye-related excitatory signals in the on direction were unchanged. This is the first report of lack of KCC2 regulation in a motoneuron type after injury, proposing a role for VEGF in KCC2 regulation and demonstrating the link between KCC2 and synaptic inhibition in awake, behaving animals.

UNASSIGNED: The stability of fixation is crucial for the development of visual function. In this study, we quantify the deviation of visual target during fixational and saccadic tasks using eye-tracking technology, reflecting the control ability and characteristics of fixational displacement among healthy adults in a convenient method.
UNASSIGNED: One hundred healthy participants aged between 18 and 55 years were recruited in the study. All participants underwent a complete ophthalmic assessment. The eye positions in the fixational and saccadic tasks were documented and analyzed by the Tobii eye-tracking system. Participants were grouped by age and gender. Targeting displacement (TD), defined as the average displacement between visual target and the mean of fixation points corresponding to that stimuli, was used to quantitatively observe fixational displacement in the horizontal and vertical directions.
UNASSIGNED: There was a strong reproducibility of TD as an indicator of fixation (ICC 0.812 to 0.891, p < 0.001). The TD in fixational task was significantly smaller than that of the saccadic task (3.884 ± 0.525 vs. 4.484 ± 0.509, p < 0.001) among normal people. Moreover, the difference of TD in the horizontal and vertical meridians was related to the nature of the task: In the fixational task, the TD in horizontal was smaller than that in the vertical (p < 0.001), whereas the TD in horizontal was larger than that in vertical in the saccadic task (p = 0.003). In the different age and gender groups: There was no significant difference between different gender and age groups in fixational task. However, during the saccadic task, males had smaller TD in the vertical direction than females (4.061 ± 0.495 vs. 4.404 ± 0.484, p = 0.002), and the average TD increased with age, mainly in the vertical direction (all p < 0.05). The fixation stability decreased significantly in the group over 50-years-old.
UNASSIGNED: By reporting the fixational displacement of different genders and ages in fixational and saccadic tasks, as well as different longitude lines among normal people, our study might provide an objective, quantitative and convenient reference index for the evaluation of fixation stability in visual impairment diseases and aging phenomenon of visual function.

Extraocular motoneurons are located in three brainstem nuclei: the abducens, trochlear and oculomotor. They control all types of eye movements by innervating three pairs of agonistic/antagonistic extraocular muscles. They exhibit a tonic-phasic discharge pattern, demonstrating sensitivity to eye position and sensitivity to eye velocity. According to their innervation pattern, extraocular muscle fibers can be classified as singly innervated muscle fiber (SIF), or the peculiar multiply innervated muscle fiber (MIF). SIF motoneurons show anatomical and physiological differences with MIF motoneurons. The latter are smaller and display lower eye position and velocity sensitivities as compared with SIF motoneurons.