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Forebrain control of the dynamics of brainstem and spinal cord networks generating rhythmic activity

Sten Grillner (PI), William Scott Thompson

The aim of this project is to understand how forebrain circuits, in particular the basal ganglia/cortex and habenulae (dopamine neurons), contribute to the selection and initiation of different motor programs. This is achieved by elucidating in the lamprey model system forebrain mechanisms that regulate the level of activity and dynamics of the brainstem command centres for locomotion, steering, and eye and orienting movements with due comparison to the mouse. The basal ganglia – habenulae – SNc/VTA network are evolutionarily conserved in practically all aspects – although with fewer neurons of each type, and is therefore an excellent experimentally amenable model for vertebrate forebrain function We will combine patch recordings of single neurons and synaptically connected neurons, with imaging of groups of identified cells during behavior in the basal ganglia including the conserved dopamine system and its control via habenulae with immunohistochemical and tracing techniques. This approach aims at defining network interactions within the forebrain and to downstream motor control areas of the brainstem and spinal cord. Detail- led multiscale compartmental modeling that extends existing brainstem - spinal cord network models will be an important component to elucidate the overall network operation from the forebrain level and downstream components. We will analyse equal numbers of male and female specimens to investigate if there are sex differences with regard to forebrain function.