MoThal · Functional exploration of the contributions of brainstem-motor thalamic pathways to motor execution and learning

Functional exploration of the contributions of brainstem-motor thalamic pathways to motor execution and learning

The ability to learn and to adapt a motor program is of fundamental importance to all species, since it enables performance of complex movements, but also to adapt these learned movements to perturbation in the environment. However, the circuits involved in these processes are poorly known. An important brain structure in this context is the cerebellum, and in particular the deep cerebellar nuclei (DCN), which are the sole output of the cerebellum. Interestingly, the DCNs project strongly to the brainstem and to the motor thalamus, two major structures in motor function. Indeed, premotor brainstem areas with projections to the spinal cord are a major locus needed for the control of movement. A recent study has shown that different brainstem nuclei connect to motor neurons innervating forelimb and/or hindlimb muscles in very specific patterns. For example, the manipulation of glutamatergic neurons in the medullary reticular formation ventral part (MdV) in mice led to specific deficits in the grasp behavior in a motor learning task, the single-food-pellet retrieval task. This same manipulation also led to deficits in an accelerating rotarod task, another motor learning task. Therefore, these results begin to suggest that specific brainstem nuclei have functional contributions to a specific aspect of a movement sequence. By their direct impact on an ongoing movement, the brainstem nuclei seems to represent unavoidable actors in the learning and adaptation of movements.On the other side of the fence is the Mthal, a ventral structure of the thalamus composed of several nuclei. These nuclei received strong projections from DCNs, and project differentially to motor cortical areas. The research on Mthal nuclei is very limited, mostly due to technical limitations needed to surmount the complexity of the intricate multi-nuclei organization of Mthal. Nevertheless, some lesion studies have shown a major contribution of Mthal in motor learning, in particular the target-reaching task and rotarod task, mirroring effects of transient manipulation of brainstem nuclei in mice in similar tasks. As such, these data suggest a complementary role of the Mthal to the brainstem in the learning and adaptation of the movement. It is therefore the purpose of this present project to elucidate the specific role of the DCNs to brainstem and DCNs to Mthal pathways in the aforementioned motor function. 3 major objectives have been set: 1, to study the anatomical connectivity between the DCNs, the brainstem and the Mthal. Not only this will bring new fundamental knowledge about poorly studied pathways, but it will also enable us to postulate and test a hypothesis on the role of a DCN-brainstem-Mthal pathway identified in motor execution adaptation. To probe these hypotheses, the 2 objective will consisted to correlate the activity of these pathways when mice is performing motor tasks, by means of in vivo calcium imaging and electrophysiological recordings. 3, the functional role of the different brainstem-Mthal pathways will be assessed through circuit manipulation and loss of function.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз