Chapter 2 - Genetic dissection of rhythmic motor networks in mice
Section snippets
Rhythmic motor circuits in the hindbrain and spinal cord
The core neuronal networks that control rhythmic respiratory and locomotor motor behaviors reside in the hindbrain and spinal cord, respectively. These CPG networks generate simple organized motor rhythms in an autonomous manner. Initial efforts to decipher the general organization of these simple motor CPGs in vertebrates relied heavily on electrophysiological and pharmacological approaches. Such efforts were greatly aided by the development of in vitro hindbrain–spinal cord preparations in
The developmental program of the caudal neuroaxis
The developmental events that pattern the caudal neural tube play a central role in assembling sensorimotor circuits in the hindbrain and spinal cord (Goulding, 2009, Jessell, 2000). The position that a progenitor cell occupies along the dorsoventral (DV) axis confers a specific genetic code to these cells and thus serves as a major determinant of cell identity (Fig. 1a). This DV patterning program segregates newborn neurons into generic populations that are arrayed as longitudinal columns
Genetically defined interneuronal populations that shape the locomotor rhythm
The identification of genetic markers for different spinal interneuronal populations has laid the foundation for functional studies aimed at assessing the contribution that genetically defined cell types make to the CPG networks controlling locomotor or respiratory rhythmogenesis (Chapter 3 in this book). These efforts have been centered on broad interneuron classes including the V0, V1, V2a, and V3 interneurons (Stepien and Arber, 2008); however, attention is now turning to subtypes within
New genetic approaches for studying motor circuits in the spinal cord
The elaboration of a genetic classification scheme for the interneuron cell types involved in spinal motor control has opened up new routes for manipulating the spinal motor system and determining how specific motor behaviors are generated. The approaches used so far involve deleting or inactivating broad interneuron classes and assessing how this affects network activity (Table 2). This is usually achieved by generating transgenic animals in which a recombination event such as Cre-mediated
Conclusion
The delineation of the transcriptional code for neuronal cell populations in the ventral spinal cord and the emergence of several genetic approaches to manipulate cells of interest have paved the way for genetically and functionally dissecting the neural circuits controlling locomotion. The embryonic building blocks that make up these motor circuits are shared between the networks controlling respiration and locomotion. Thus, understanding how neuronal cell populations that comprise the
Acknowledgments
K. S. G. is funded by a Feodor Lynen Fellowship from Alexander von Humboldt Foundation. Research in the Goulding lab is supported by grants from the National Institutes of Health (NS031249, NS031978 and NS037075) and the Christopher and Dana Reeve Foundation. We would particularly like to thank Tim Hendricks, Floor Stam, and other members of the Goulding Lab for allowing us to cite their unpublished findings.
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The specification and generation of neurons in the ventral spinal cord
2020, Patterning and Cell Type Specification in the Developing CNS and PNS: Comprehensive Developmental Neuroscience, Second EditionA subset of interneurons required for Drosophila larval locomotion
2016, Molecular and Cellular NeuroscienceCitation Excerpt :Despite progress in understanding how axons are guided to their final target destinations to eventually synapse with their appropriate target cells, we have little understanding of how neural circuits are actually assembled during development. This is true even for well-studied circuits such as those underlying “simpler” rhythmic movements such as locomotion, breathing and digestion (Grossmann et al., 2010; Selverston, 2010). We are developing Drosophila larval locomotion as a model system to study circuit function and development.
Gene Maps and Related Histogenetic Domains in the Forebrain and Midbrain
2015, The Rat Nervous System: Fourth EditionSpinal inhibitory circuits and their role in motor neuron degeneration
2014, NeuropharmacologyCitation Excerpt :V2a regulate burst robustness and left-right coordination during motor patterns, but the function for V2b and V2c remain to be identified. V3 are ventral (V3v) and dorsal (V3D), commissural excitatory interneurons, each one with different electrophysiological properties, that distribute excitatory drive towards both halves of spinal cord, maintaining a regular and balanced motor rhythm during walking (Grossmann et al., 2010; Zhang et al., 2008). Spinal neuronal networks have been organized in a model for its study and understanding, known as central pattern generators (CPG), which are delimited neuronal networks that generate the timing, phasing, and intensity cues to drive motor neuron output for simple rhythmic behaviors such as locomotion, mastication, and respiration (Harris-Warrick, 2011).
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equal contribution.