Proprioception in Extraocular Muscles of Mammals

To know the position of targets in the visual space is of practical importance for activities in every day life. Simple tasks such as reaching for an object as well as more complex tasks such as driving a car need spatial information. To exactly localize the position of objects, our central nervous system needs information of the eye`s position in the orbit to form a context for the retinal scene. It is supposed that information about the eye position comes from sensory organs (proprioceptors) in the extraocular muscles (EOMs). Evidence from man, and other mammals indicates that classical proprioceptors (muscle spindles and Golgi tendon organs) are absent in most species. Dogiel (1906) was one of the first who described palisade endings (myotendinous cylinders) in the EOMs of several mammals and man. So far, palisade endings have been observed in the EOMs of all species investigated including man, and it has been supposed that palisade endings could be an alternative form of sensory ending. In fact, although physiological evidence is missing, there is nowadays consensus that palisade endings are sensory and some authors claim that they are the principal proprioceptor type in EOMs. In our previous FWF-project we have analyzed the molecular characteristics of palisade endings. Utilizing immunohistochemical methods, we have proven that palisade endings are cholinergic. In principle, our surprising findings allow two interpretations: Palisade endings are cholinergic-sensory structures or palisade endings are effector organs involving collagen fibrils. The question about the functional significance of palisade endings is re- opened. Up to now there is uncertainty about the central connections of palisade endings. If the cell bodies of the nerve fibers supplying palisade endings are located in the trigeminal ganglion, palisade endings should be sensory, whereas, if the cell bodies are in the oculomotor nuclei, then they would be motor. The applied project seeks to verify both hypotheses. Thus, we will directly test the hypothesis that palisade endings are motor by determining whether they are axons of motor neurons (AIM 1). We will also test the counterhypothesis that palisade endings are sensory by determining whether they are axons of trigeminal sensory neurons (AIM 2). The experiments would complement our previous findings on the molecular characteristics of palisade endings. Palisade endings are also found in the EOMs of man. The distal part of EOM tendons containing palisade endings is removed in many surgical procedures to treat strabismus. Other strabismus surgeons fold the tendon instead of partial resection in order to preserve the palisade endings. Our recent findings that palisade endings are putative effectors might be interpreted that resection of the EOM tendons has no side effects. Knowledge of the functional significance of palisade endings would also have clinical impact.

In the present research project we continued our prior investigations and showed the special nerve endings (palisade endings) in eye muscle of mammals exhibit motor characteristics.To exactly localize visual targets in space, the brain needs information in which direction our eyes are pointing. It is supposed that such information comes from sense organs (proprioceptors) within the eye muscles. Surprisingly, classical proprioceptors which are common in skeletal muscles are absent in the eye muscles of most mammalian species with the exception of even-toed ungulates. Instead of that, palisade endings have been found in all species so far investigated.In literature it is supposed that palisade endings are sense organs. In our prior project which was supported by the FWF, we analyzed the molecular features of palisade endings. Our data show that palisade endings exhibit molecular characteristics which are more compatible with motor nerves endings. Our surprising findings reopened the debate about the function of palisade endings.It was the aim of the present project to clarify from where the axons forming palisade endings originate in the brain. Specifically, if palisade endings are sensory, the origin of palisade endings should lie in a sensory area (trigeminal ganglion) of the brain. If palisade endings are motor, the origin should be in a motor area (motor nuclei of the eye muscles) of the brain. To clarify this question we used neuronal tracing experiments. Such techniques allow to stain nerves selectively and to trace them from the origin to their final destination. In combination with immunohistochemical methods we could show that palisade endings originate from the eye muscles motor nuclei and the results support the idea that palisade endings are effectors. Functionally our results might be interpreted that palisade endings regulate fine eye movements which are necessary for reading or focusing objects. Our findings also have clinical impact. As palisade endings are also present in humans, they are of particular interest for strabismus surgery.