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Control of locomotion by the mesencephalic locomotor region, basal ganglia and central amygdala

Abstract

The ability to locomote through the environment is fundamental to most animal species’ survival. Vertebrates ranging from lamprey to humans share common circuitry involved in sending signals from the brain to the spinal cord to control central pattern generators (CPGs). These CPGs in turn control the alternating muscle activations that result in walking, slithering, swimming or flying. The mesencephalic locomotor region (MLR) is putatively the final node in the central nervous system that integrates locomotor information from various brain regions and sends locomotor commands to the periphery. Originally defined functionally as a brainstem region in which electrical stimulation drives locomotion with short latencies, the MLR has been found in lamprey, stingray, dogs, birds, guinea pigs, mice, rats, cats, and dogs among other species. The MLR receives input from a variety of areas which all likely affect whether or not and how fast an animal locomotes. In this dissertation we will explore both the MLR and two specific afferent connections, one from the basal ganglia (BG) and one from the central amygdala (CeA) which are demonstrated to control locomotion through the MLR. In Chapter 1 we will provide an introduction to the MLR, the BG and the CeA. In Chapter 2 we will dissect the circuitry of the mouse MLR to provide evidence for which nuclei and MLR cell types are responsible for the results observed during electrical stimulation. In Chapter 3 we will look at how the BG controls locomotion through the MLR, taking time to dissect the two canonical pathways which are hypothesized to bidirectionally control locomotion as well as movement in general. Chapter 4 will provide evidence for a “stop” signal sent from the CeA to the MLR that determines whether or not an animal will run in response to aversive stimuli. Finally, in Chapter 5 we discuss the significance of the work and look at how it might shape the direction of future experiments.

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