Proprioception in Extraocular Muscles of Mammals

The eyes are the most complex organs of the body and allow us to perceive objects in proper shape, color, and detail. Besides that, individuals know where objects are located in space and this is fundamental to precisely reach out for them or avoid obstacles. For the spatial localization of objects, the brain needs visual information from the retina and additional information in which direction the eyes are pointing. The eyes are moved by three pair of eye muscles. It is supposed that eye position information comes from special sensors (proprioceptors) in eye muscles. Surprisingly, classical proprioceptors are absent in eye muscles of most mammals and instead a specialized nerve ending, the so-called palisade ending is present. With the exception of rodents, palisade endings are regularly found in mammals including man. For many years there has been consensus that palisade endings are sensors providing the brain with eye position information. The sensory role of palisade endings was put into question when we showed that palisade endings exhibit molecular characteristics of motor terminals and originate from the motor nuclei in the brain stem. These novel findings have reopened the discussion about the function of palisade endings and it is still not clear whether they are sensory or motor. The present project will continue our investigations on palisade endings and will be done in international cooperation with the Profs. Angel Pastor and Rosa de la Cruz from the University of Seville. In one part of the project we will test whether the development of palisade endings is genetically programmed or influenced by external (epigenetic) factors. The core of the project is to analyze the function of palisade endings. Based on two hypotheses, we will test whether palisade endings have a sensory or motor function. For analyses we will use techniques which are currently state of the art and include molecular and electrophysiological experiments. Present findings will help to settle a long-lasting discussion about the function of palisade endings. Furthermore, palisade endings are also found in human EOMs and are destroyed in many surgical procedures to treat strabismus. Thus, knowledge of the functional significance of palisade endings would be of particular interest for strabismus surgeons.

The eye allows us to perceive the environment. However, vision is only useful if one knows one's ocular orientation. That is, the ability to determine the position of objects in space is based on the knowledge of one's own eye orientation. This information is important in everyday life. For example, if an object is in front of me, I need to move aside; if it is beside me, I can continue on my way. The eyes are moved by eye muscles and it is assumed that special sensors in the muscles provide eye position information. Candidates for the perception of eye position are specialized nerve endings (palisade endings) located at the muscle-tendon junction of the eye muscles. However, our research group has shown that palisade endings have molecular characteristics of motor nerve endings and originate in the oculomotor nucleus. These findings have led to the re-examination of palisade endings, as their precise function remains ambiguous. It is noteworthy that palisade endings are not present at birth and undergo development during the initial postnatal months. The present project had 2 aims. Firstly, to investigate whether the development of the palisade endings can be influenced by external factors and secondly, to clarify the function of these structures by molecular and physiological experiments. In the first objective of the project (development of the palisade endings), a group of animals grew up in darkness and in another animal group the eye movements were blocked. Findings showed that light deprivation had no influence on the development of palisade endings. However, eye blocking significantly delayed the palisade ending development. This can be interpreted that eye movements rather than vision play a crucial role in the maturing of palisade endings. In the second project objective (function of palisade endings), we showed through the use of molecular markers that palisade ending express key proteins, which are involved in neurotransmitter (acetylcholine) release. Surprisingly, receptors for acetylcholine were not associated with palisade endings. This suggests that acetylcholine set free from palisade endings binds to a hitherto unknown receptor or has a receptor-independent, modulatory function. In a subsequent physiological experiment, electrical stimulation was performed at the myotendinous junction (the site of the palisade endings). Recordings were conducted in the oculomotor nucleus to ascertain whether signals from the palisade endings reach the brain. However, these attempts failed to elicit any signals from the palisade endings, indicating that they do not directly interface with the brain. To summarize, although the exact function of palisade of palisade endings is still elusive, there is evidence that they play a role in convergence eye movements which are necessary when focusing near objects. Clearly, further experiments are warranted to clarify the exact role of palisade endings.