Werner Graf, M.D., Ph.D.
Office: Numa P. G. Adams bldg., Room: 2307
Office Telephone: 202-806-3325
Laboratory: Numa P. Adams bldg., Room: 2508-B
MD, Albert-Ludwigs-University, Freiburg, Germany (1975)
PhD, Albert-Ludwigs-University, Freiburg, Germany (1977)Postdoctoral Fellow, New York Univ. Medical School, New York, NY (1979-1981)
- General Physiology
- Biomedical Science
- Dental Physiology
NSF-PIRE (Program in International Research and Education), “PIRE Program in Cognitive, Computational and Systems Neuroscience”. Co-PI. 2007-2014.
NSF-IGERT (Integrative Graduate Education and Research Traineeship Program), “Dynamics of Behavioral Shifts in Human Evolution: Brains, Bodies and Ecology" Co-P.I. 2008-2014.
Dr. Graf’s scientific activities are focused on the perception of movement, and the sensory-motor transformations in context of differentiation of active versus passive movements, as well as motor learning and developmental aspects. A crucial sensory system for the detection of movement, whose existence we are unaware of under normal circumstances, is our sense of balance, i.e., the labyrinth, or the vestibular system. We become acutely aware of this sense only, when it malfunctions, resulting e.g. in vertigo, motion sickness (sea sickness, space motion sickness in astronauts, etc.).
Neuronal Correlates of Movement Perception
Neuronal correlates of movement detection and perception of visual and somatosensory qualities have been demonstrated in many areas of the so-called "dorsal visual stream areas" (MT, MST, LIP, VIP, etc.). The role and importance of vestibular signals for these functions have only recently been shown in recordings from VIP (ventral intraparietal area) conducted in Dr. Graf’s laboratory. Area VIP of macaque monkeys is located in the fundus of the intraparietal sulcus. It bridges the gap between the "dorsal visual processing stream" (e.g. LIP, lateral intraparietal area) and the somatosensory and premotor system (MIP). Area VIP is thus considered to play an important role in the analysis of self-motion and multimodal representation of the three-dimensional movement space. Our recordings revealed directionally selective responses for vestibular stimulation, and to visual as well as tactile stimulation.
The experiments planned for the near-future will investigate the role of vestibular signals during active versus passive semi-constrained head movements (recordings in MT/MST, VIP, and the vestibular cortices: 2v and PIVC).
Neuronal Circuits Underlying Perceptive and Motor Functions
We have begun to visualize entire context-related neuronal circuits with the retrograde transneuronal tracing using rabies virus. In experiments in guinea pigs and primates we were able to show the entire neuronal circuitry involved in horizontal eye movement control. The results signal an ever increasing complexity of afferent pathways and control circuits converging onto the different layers of the investigated networks and onto the final motoneuronal pathway. In addition to the well-known motor pathways, circuitry involved in navigation (hippocampus), movement perception (cortical areas), motivation, etc., were revealed as well. Recent intracortical injections of the tracer revealed the afferent pathways to VIP/MIP and MT/MST regions.The full potential of this powerful method to determine entire functional neuronal networks involved in specific behaviors will be accomplished by perfecting central injection techniques, and the development of intracellular injections. Applying this technology to neuronal development will certainly lead to new insights in that dynamic field of research. In future applications, we are envisioning to employ this technique to demonstrate the missing and/or altered circuits and neuronal elements in genetically modified animals, such as knock-out mutants, in order to clarify the pathophysiology of related syndromes and behaviors.
Adaptation and Learning
In this context, we make use of a particular animal model offered by Nature: the flatfish. Flatfish are a natural paradigm for studying adaptive changes of compensatory eye movements (the vestibulo-ocular reflex, VOR). During metamorphosis, flatfish tilt 90 degrees to one side or the other to become bottom-adapted adult animals. In this position, the labyrinths are rotated 90 degrees relative to their premetamorphic orientation in space. Structurally, this arrangement requires a neuronal pathway from the horizontal semicircular canals to muscles that move the eye vertically. The morphological substrate subserving adaptation of the VOR in post-metamorphic (adult) flatfish was obtained with a number of morphological and electrophysiological methods. This system allows the study of a closely defined developmental plasticity process. Single cell morphology of vestibular neurons revealed a unique innervation pattern linking horizontal vestibular neurons to vertical eye muscles. We have furthermore discovered an interesting asymmetry in vestibular nuclei innervation in these animals based on swimming behavior after hemilabyrinthectomy. In future experiments of the ontogenetic development of eye movement circuits in flatfish, we will determine the cell lineages of the development of this particular vestibulo-oculomotor connectivity. The flatfish is an unprecedented model in vertebrate hierarchy to understand mechanisms of adaptation to a changing life situation.
Vestibular Stimulation Apparatus
We have acquired a NASA-grade vestibular stimalation apparatus that allows various combinations of angular and linear accelaration stimuli about vertical and horizintal axes in order to test human spatial orientation, and compensatory eye and head movements. The apparatus can be certified to be used as a diagnostic tool for vertigo patients and accompanying vestibular rehabilitation.