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IS-DAAD-Forskerutveksl. Norge-Tyskland

Dissecting the developing vestibulo-ocular reflex circuit: Pharmacogenetic and optogenetic manipulation

Tildelt: kr 34 661

A fundamental question in neuroscience is how neuronal circuits are assembled during embryonic and fetal development. Critical features include the establishment of functionally appropriate patterns of synaptic connections and a proper balance between exc itatory and inhibitory connections. Sensorimotor reflex circuits provide excellent models for the study of these features since they involve highly specific connections from afferents onto premotor neurons and from premotor neurons onto motoneurons (Glove r 2000). The vestibulo-ocular reflex (VOR) arc is a particularly tractable sensorimotor reflex circuit in this regard because it comprises a well-described pattern of polysynaptic connections with a stereotyped mapping of sensory inputs to motor outputs. Thus, the VOR circuit provides an excellent system for studying both the molecular mechanisms that specify synaptic connections during development and the acqusition of proper balance in excitation and inhibition, perturbations of each of which can lead t o inappropriate activity such as seen in various human neurological disorders (movement disorders, spasticity, epilepsy). In this project two laboratories, one in Oslo and one in Munich, will collaborate to establish genetically mediated pharmacological and optical manipulations of activity in specific neurons and neuron groups in the VOR circuit. This will significantly advance our understanding of VOR function and development through 1) a more precise dissection of synaptic interactions within the ind vidual sensorimotor channels of the VOR, including characterization of patterns of synaptic convergence, and 2) temporally controlled perturbance of dynamic activity levels to assess their effects on synaptic patterning and scaling. This will provide insi ght into the mechanisms of synapse formation, patterning and balance, which are of high general relevance for the development of circuits in all parts of the brain.

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IS-DAAD-Forskerutveksl. Norge-Tyskland