Brainstem circuits involved in skilled forelimb movements

Abstract

Movement is the main output of the nervous system as well as the fundamental form of interaction animals have with their environment. Due to its function and scope, movement has to be characterized by both stability and flexibility. Such apparently conflicting attributes are reflected in the complex organization of the motor system, composed of a vast network of widely distributed circuits interacting with each other to generate an appropriate motor output. Different neuronal structures, located throughout the brain, are responsible for producing a broad spectrum of actions, ranging from simple locomotion to complex goal directed movements such as reaching for food or playing a musical instrument. The brainstem is one of such structures, holding considerable importance in the generation of the motor output, but also largely unexplored, due to its less-than-accessible anatomic location, functional intricacies and the lack of appropriate techniques to investigate its complexity. Despite recent advances, a deeper understanding of the role of brainstem neuronal circuits in skilled movements is still missing. In this dissertation, we investigated the involvement of the lateral rostral medulla (LatRM) in the construction of skilled forelimb behaviors. The focus of my work was centered on elucidating the anatomical and functional relationships between LatRM and the caudal brainstem, and specifically on the interactions with the medullary reticular formation, considering both its ventral (MdV) and dorsal subdivisions (MdD). In summary, we reveal the existence of anatomically segregated subpopulations of neurons in the lower brainstem which encode different aspects of skilled forelimb movements. Moreover, we show that LatRM neurons are necessary for the correct execution of skilled motor programs and their activation produces complex coordinated actions. All this evidence suggests that LatRM may be a key orchestrator for skilled movements by functioning as integration center for upstream signals as well as coordinator by selecting the appropriate effectors in the lower medulla and the spinal cord

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