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Transneuronal tracing reveals the modular building blocks of the nervous system

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The functioning of entire neuronal assemblies is one of the foremost interests of current research that forms the leading edge in today's neuroscience, imaging technique, computer sciences and robotics. Although neuronal network theories introduce algorithms that are thought to resemble actual nervous system operations, functional mechanisms of such neuronal nets are still elusive, largely because of a lack of knowledge about connectivity of all involved nervous structures. This information can now be provided by a new transneuronal tracing technology with rabies virus, which was developed in Europe. This technology offers for the first time the opportunity to describe functionally related neuronal networks in their entirety, i.e. the hierarchy of their building blocks, accessory elements and parallel processing characteristics.
The proposed project will represent the first large-scale application of this technology to the study of the primate brain, for which the eye movement network was selected as a model system. Aside from its importance in daily life, this system has the advantage that some of its elements are already well described, constituting established sub-systems. At the same time, clarification is needed concerning higher order processing (e.g. cortical areas) and cell communication within and between the various sub-systems. The oculomotor system is also an excellent example of the modern concept of modular organization of central nervous operations. Such spatial modules exist in the spatial orientation planes of the three pairs of extra-ocular muscles. These form a natural reference frame that is reflected in the structure and function of the underlying neuronal circuits. Viral transneuronal tracing from two prototypical eye muscles, one horizontal (lateral rectus) and one vertical (superior rectus), with complementary approaches (functional characterization of specific subsystems with deoxyglucose and electrophysiology), will clarify the modular organization of the different oculomotor networks in monkeys and provide a clear understanding of their functional role in eye movement control, vision, vi-quo-motor coordination and cognitive and attentional processes. Different work packages will examine: 1) the vestibulo-ocular system producing reflex eye movements during passive motion; 2) the velocity-to position integration network involved in generation of eye position signals; 3) the saccadic network producing rapid eye movements for orienting and reflex functions; 4) the cerebellar system subserving adaptive plasticity and motor learning; 5) the cortical networks involved in motion perception, attention processes and voluntary control of saccadic and smooth pursuit eye movements. The results will be correlated with findings from human brain material of clinical cases with oculomotor disorders.
The deliverables will illustrate the entire architecture of eye movement networks, i.e. from simple reflex mechanisms to perceptual functions, thus giving incentives in the clinical-medical and industrial fields for oculomotor deficits and rehabilitation of human patients, as well as for computer science with respect to neuro-computers, artificial intelligence, and robotics. The realization of this collaborative effort will give European science and technology a distinctive competitive advantage, because the necessary multi-disciplinary consortium could not have been formed anywhere else at this point in time. The proposed project can be carried out only if supported by the European Commission, because none of the participating countries alone would be able to provide the necessary combination of scientific skills and facilities. Furthermore, none of the individual countries is prepared to support on its national funding schemes the multi-national collaborative effort required for realizing such a project.

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