graf

Project Summary

The overall goal of specific experiments planned for the next 7-10 years is to describe the neuronal structure-function relationship of spatially and temporally coordinated eye and head movements, and the perception of self-motion by analyzing intrinsic reference frame systems and related neuronal networks in functional, ontogenic and phylogenetic contexts. Thus, almost all experimental scenarios include comparative studies in different vertebrates.

At present, ongoing and planned experiments investigate :

1) The sensorimotor transformations involved in the spatial coordination of compensatory eye and head movements: these experiments use three-dimensional natural vestibular stimulation in concert with intracellular recordings and staining methods of second-order vestibular neurons in cats. The data obtained thus far, allowed us to develop the first fairly good working hypothesis about the actual mechanisms of coordinate transformations in a sensorimotor system.

2) The central representation of the visual world in reference to compensatory eye and head movements and their underlying sensory and motor systems in different vertebrates, including motor learning paradigms: these experiments use three-dimensional optokinetic stimulation in concert with extracellular recordings in the olivo-cerebellar system of normal rabbits and monkeys, and during learning paradigms.

3) The structure-function relationship of vestibular neurons to spatially coordinated compensatory and voluntary eye movements: in these experiments the neurophysiological and structural parameters of second-order vestibular neurons will be assessed in relation to three-dimensional compensatory and voluntary eye movements in monkeys using intracellular recording and staining methods.

4) The ontogenetic development of eye movement circuits in elasmobranchs and teleosts, particularly the flatfish: the cell lineages and development of the vestibulo-oculomotor connectivity will be studied using immunohistochemistry (GABA, glycine), thymidine autoradiography and molecular biology methodology (GAP-43, in situ hybridization, PCR cloning). Furthermore, the ontogenetic development of specific behaviors, e.g., eye movements, will be determined. The flatfish, in particular, is an unprecedented model in vertebrate hierarchy to understand mechanisms of adaptation to a changing life situation.

5) The ontogenetic development of the neuronal basis for central representation of the visual world: in these experiments, the sensory basis for establishing the characteristic optokinetic reference frames as already shown in the olivo-cerebellar and vestibular systems will be determined. The specific paradigms include dark-rearing of rabbits, and lesion studies of the vestibular and extraocular muscle proprioceptors in concert with extracellular recordings.

6) The specialized horizontal eye movement pathways: these studies will describe the vestibulo-oculomotor circuitry in elasmobranchs using established techniques. Since the extraocular motoneuron distribution in elasmobranchs is different from other vertebrates, they provide and important model to study convergent evolution, and as such the workings of natural selection. These experiments are also aimed at describing the possible mechanisms underlying and allowing ocular frontalization in vertebrates, including the acquisition of a fovea and stereopsis.

7) The phylogeny of the head-neck ensemble and head movement strategies including eye-head coordination in different vertebrates, the biomechanical basis of vertebrate head-neck posture and the question of "subjective verticality": these experiments combine cineradiography of behaving animals, lesion and learning paradigms, and electrophysiological techniques, e. g., EMG and neuron recordings.

8) The neuronal correlates of three-dimensional self-motion perception and of psychophysical phenomena such as linear- and circular vection: these experiments use extracellular recordings in monkey neocortex, in particular parietal areas, as well as depth electrode and quantitative EEG-analysis combined with neuro-imaging in humans.

9) Global description of the entire neuronal network involved in eye movement control: these experiments use transneuronal tracing with rabies virus in primates to describe all inputs converging on a given eye muscle or central structure.

In order to achieve these goals, a wide range of neurobiological methods have been and will continue to be used in my laboratories and in collaboration with other investigators. These approaches include neuroethological techniques (analysis of behavior in normal and lesioned animals) in conjunction with video-, film-, and x-ray cinematography; neurophysiological techniques (electrical central and peripheral stimulation, natural visual and vestibular stimulation, field potential analysis, single cell extra-and intracellular recordings, eye movement registration with the magnetic search coil, quantitative EEG); neuroanatomical techniques (extra- and intracellular horseradish peroxidase application, 2-deoxy-glucose and thymidine autoradiography, immunocytochemistry, transneuronal labeling with a virus tracer, neuro-imaging); modeling of the functional properties of sensory-motor systems (matrix analysis, tensor analysis), and combinations of the above.
These studies make use of monkeys, cats, rabbits and various elasmobranch and bony fish species in acute and chronic preparations, as well as behavioral paradigms in humans.