Robert Baker

Predictive motor control is ubiquitously employed in animal kingdom to achieve rapid and precise motor action. In most vertebrates large, moving visual scenes induce an optokinetic response (OKR) control of eye movements to stabilize vision. In goldfish, the OKR was found to be predictive after a prolonged exposure to temporally periodic visual motion. A recent study showed the cerebellum necessary to acquire this predictive OKR (pOKR), but it remained unclear as to whether the cerebellum alone was sufficient. Herein we examined different fish species known to share the basic architecture of cerebellar neuronal circuitry for their ability to acquire pOKR. Carps were shown to acquire pOKR like goldfish while zebrafish and medaka did not, demonstrating the cerebellum alone not to be sufficient. Interestingly, those fish that acquired pOKR were found to exhibit long-lasting optokinetic after nystagmus (OKAN) as opposed to those that didn’t. To directly manipulate OKAN vestibular-neurectomy was performed in goldfish that severely shortened OKAN, but pOKR was acquired comparable to normal animals. These results suggest that the neuronal circuitry producing OKAN, known as the velocity storage mechanism (VSM), is required to acquire pOKR irrespective of OKAN duration. Taken together, we conclude that pOKR is acquired through recurrent cerebellum-brainstem parallel loops in which the cerebellum adjusts VSM signal flow and, in turn, receives appropriately timed eye velocity information to clock visual world motion.

Computational capability and connectivity are key elements for understanding how central vestibular neurons contribute to gaze-stabilizing eye movements during self-motion. In the well-characterized and segmentally distributed hindbrain oculomotor network of goldfish, we determined afferent and efferent connections along with discharge patterns of descending octaval nucleus (DO) neurons during different eye motions. Based on activity correlated with horizontal eye and head movements, DO neurons were categorized into two complementary groups that either increased discharge during both contraversive (type II) eye (e) and ipsiversive (type I) head (h) movements (e_IIh_I) or vice versa (e_Ih_II). Matching time courses of slow-phase eye velocity and corresponding firing rates during prolonged visual and head rotation suggested direct causality in generating extraocular motor commands. The axons of the dominant e_IIh_I subgroup projected either ipsi- or contralaterally and terminated in the abducens nucleus, Area II, and Area I with additional recurrent collaterals of ipsilaterally projecting neurons within the parent nucleus. Distinct feedforward commissural pathways between bilateral DO neurons likely contribute to the generation of eye velocity signals in e_Ih_II cells. The shared contribution of DO and Area II neurons to eye velocity storage likely represents an ancestral condition in goldfish that is clearly at variance with the task separation between mammalian medial vestibular and prepositus hypoglossi neurons. This difference in signal processing between fish and mammals might correlate with a larger repertoire of visuo-vestibular-driven eye movements in the latter species that potentially required a shift in sensitivity and connectivity within the hindbrain-cerebello-oculomotor network. NEW & NOTEWORTHY We describe the structure and function of neurons within the goldfish descending octaval nucleus. Our findings indicate that eye and head velocity signals are processed by vestibular and Area II velocity storage integrator circuitries whereas the velocity-to-position Area I neural integrator generates eye position solely. This ancestral condition differs from that of mammals, in which vestibular neurons generally lack eye position signals that are processed and stored within the nucleus prepositus hypoglossi.

Predictive motor control is essential to achieve rapid and precise motor action in all vertebrates. Visuomotor transformations have been a popular model system to study the underlying neural mechanisms, in particular, the role of the cerebellum in both predictive and gain adaptations. In all species, large-field visual motion produces an involuntary conjugate ocular movement facilitating gaze stabilization called the optokinetic response. Gain adaptation can be induced by prolonged optokinetic visual stimulation; and if the visual stimulation is temporally periodic, predictive behavior emerges. Two predictive timing components were identifiable in this behavior. The first was prediction of stimulus initiation (when to move) and the other was stimulus termination (when to stop). We designed visual training that allowed us to evaluate initiation and termination independently that included the recording of cerebellar activity followed by acute and chronic cerebellar removal in goldfish of both sexes. We found that initiation and termination predictions were present in the cerebellum and more robust than conflicting visual sensory signals. Each prediction could be acquired independently, and both the acquisition and maintenance of each component were cerebellar-dependent. Subsequent analysis of the neuronal connectivity strongly supports the hypothesis that the acquired eye velocity behaviors were dependent on feedforward velocity buildup signals from the brainstem, but the adaptive timing mechanism itself originates within the circuitry of the cerebellum.SIGNIFICANCE STATEMENTPredictive and rapid motor control is essential in our daily life, such as in the playing of musical instruments or sports. The current work evaluates timing of a visuomotor behavior shown to be similar in humans as well as goldfish. Given the latter species' known brainstem cerebellar neuronal connectivity and experimental advantage, it was possible to demonstrate the cerebellum to be necessary for acquisition and maintenance of both the initiation and termination components of when to move and to stop. All evidence in this study points to the adaptive predictive control site to lie within the cerebellar circuitry.

X-ray mirror quality has continuously improved over the past 20 years and manufacturers are now able to provide long mirrors with slope errors below 0.2 μrad. Nevertheless, these mirrors are mounted on holders or even mechanical benders to adjust their curvature and their intrinsic quality must be preserved from any parasitic deformation such as twist. The most direct method of detecting these deformations is to measure the 3D topography of the optical surface. At the ESRF metrology laboratory, three different stitching systems are under development based on Fizeau sub-aperture measurements. The first one consists of measuring long flat mirrors, the second based on the relative angle determinable stitching interferometry (RADSI) method developed at SPring-8 is aimed primarily at the measurement of short mirrors with strong curvature down to a few meters, and the last, also based on the RADSI method, is dedicated to characterize longer mirrors with intermediate curvature. For each method we will describe the measurement setup and discuss first results obtained. Micro-stitching interferometry is also currently used at the ESRF metrology laboratory. The technique is suitable for measuring deeply curved aspherical profiles and will be illustrated with results from a Kirkpatrick-Baez mirror system for nano-focusing.

We investigated the contribution of blood vessel formation and neuronal excitability to the development of functional neural circuitry in larval zebrafish by analyzing oculomotor performance in response to visual and vestibular stimuli. To address the dependence of neuronal function on the presence of blood vessels, we compared wild type embryos to reck and cloche mutants that lacked intracerebral blood vessels. To test how neuronal excitability impacts neuronal development and intracerebral vascularization, we blocked neural activity using Tetraodotoxin (TTX) and Tricaine. In reck mutants, we found both slow phase horizontal tracking and fast phase resets with only a slightly reduced amplitude and bandwidth. Spontaneous saccades, eye position holding and vestibular gravitoinertial induced eye rotation were also present. All of these behaviors except for visual tracking were observed in cloche mutants that lacked any head vasculature. Thus, numerous oculomotor neuronal circuits spanning the forebrain, midbrain and hindbrain compartments, ending in motor innervations of the eye muscles, were correctly formed and generated appropriate oculomotor behaviors without blood vessels. However, our observations indicate that beginning at approximately six days, circulation was required for sustained behavioral performance. We further found that blocking neuronal excitability with either TTX or Tricaine up to 4-5 days post fertilization did not noticeably interfere with intracerebral blood vessel formation in wild type larvae. After removal of drug treatments, the oculomotor behaviors returned within hours. Thus, development of neuronal circuits that drive oculomotor performance does not require neuronal spiking or activity. Together these findings demonstrate that neither vascularization nor neuronal excitability are essential for the formation of numerous oculomotor nuclei with intricately designed connectivity and signal processing. We conclude that a genetic blueprint specifies early larval structural and physiological features, and this developmental strategy may be viewed as a unique adaptation required for early survival.

Hox genes have been shown to be essential in vertebrate neural circuit formation and their depletion has resulted in homeotic transformations with neuron loss and miswiring. Here we quantifiy four eye movements in the zebrafish mutant valentino and hox3 knockdowns, and find that contrary to the classical model, oculomotor circuits in hindbrain rhombomeres 5–6 develop and function independently of hox3 genes. All subgroups of oculomotor neurons are present, as well as their input and output connections. Ectopic connections are also established, targeting two specific subsets of horizontal neurons, and the resultant novel eye movements coexists with baseline behaviours. We conclude that the high expression of hox3 genes in rhombomeres 5–6 serves to prevent aberrant neuronal identity and behaviours, but does not appear to be necessary for a comprehensive assembly of functional oculomotor circuits.

The vertebrate hindbrain develops as a series of well‐defined neuroepithelial segments or rhombomeres. While rhombomeres are visible in all vertebrate embryos, generally there is not any visible segmental anatomy in the brains of adults. Teleost fish are exceptional in retaining a rhombomeric pattern of reticulospinal neurons through embryonic, larval, and adult periods. We use this feature to map more precisely the segmental imprint in the reticular and motor basal hindbrain of adult goldfish. Analysis of serial sections cut in three planes and computer reconstructions of retrogradely labeled reticulospinal neurons yielded a segmental framework compatible with previous reports and more amenable to correlation with surrounding neuronal features. Cranial nerve motoneurons and octavolateral efferent neurons were aligned to the reticulospinal scaffold by mapping neurons immunopositive for choline acetyltransferase or retrogradely labeled from cranial nerve roots. The mapping corresponded well with the known ontogeny of these neurons and helps confirm the segmental territories defined by reticulospinal anatomy. Because both the reticulospinal and the motoneuronal segmental patterns persist in the hindbrain of adult goldfish, we hypothesize that a permanent “hindbrain framework” may be a general property that is retained in adult vertebrates. The establishment of a relationship between individual segments and neuronal phenotypes provides a convenient method for future studies that combine form, physiology, and function in adult vertebrates. J. Comp. Neurol. 522:2446–2464, 2014.

Central vestibular neurons form identifiable subgroups within the boundaries of classically outlined octavolateral nuclei in primitive vertebrates that are distinct from those processing lateral line, electrosensory and auditory signals. Each vestibular subgroup exhibits a particular morpho-physiological property that receives origin-specific sensory inputs from semicircular canal and otolith organs. Behaviorally characterized phenotypes send discrete axonal projections to extraocular, spinal and cerebellar targets including other ipsi- and contralateral vestibular nuclei. The anatomical locations of vestibuloocular and vestibulospinal neurons correlate with genetically defined hindbrain compartments that are well conserved throughout vertebrate evolution though some variability exists in fossil and extant vertebrate species. The different vestibular subgroups exhibit a robust sensorimotor signal processing complemented with a high degree of vestibular and visual adaptive plasticity.