Connectivity and Regional Distribution of Constituent Cells of the Mammalian Locomotor Central Pattern Generator

• Author / Creator

  Griener, Anna L

• The mammalian spinal cord contains a network of neurons capable of generating the rhythm and coordinating the complex motor pattern which underlies overground locomotion. This network, called the locomotor central pattern generator (CPG), can operate in isolation from afferent input and descending drive from higher centres of the central nervous system. Historically, investigations of the interneurons which comprise the locomotor CPG have relied on blind recording from spinal interneurons of the adult cat or the neonatal rodent. Molecular genetic approaches have recently been adopted to classify spinal cord interneurons into a defined set of cardinal populations based on shared embryonic origin. Work presented in this thesis investigates the network composition of the neonatal mouse locomotor CPG. First, the firing behaviour, distribution, and morphology of unidentified locomotor-related lamina VII interneurons is examined to elucidate the general organizational principles governing the CPG. Second, using a unique TgDbx1Cre; ROSA26EFP; Dbx1LacZ transgenic mouse model, the genetically-defined V0 and dI6 interneurons are investigated. Overall our findings demonstrate that within the spinal cord there is a differential distribution and network interconnectivity between interneurons which serve distinct functions. Among the unidentified rhythmically active lamina VII interneurons, putative rhythm generating (pRG) cells are located more medially and extend short processes towards nearby interneurons whereas putative pattern forming (pPF) cells are found laterally and extend long processes in the direction of the lateral motor pools. Investigation of the diversity between the V0V and V0D subpopulations indicates each population uses a distinct neurotransmitter, is differentially innervated by primary afferent, and follows unique synaptic pathways to contralateral motorneurons. The difference between the activity of V0V and V0D interneurons during fictive locomotion leads us to hypothesize that V0V cells are primarily responsible for left-right coordination while V0D cells may serve a critical role in the integration of sensory information. Examination of the dI6 population indicates they are a predominantly commissural interneuron population, though premotor dI6 cells target motorneurons bilaterally. Rhythmically active dI6 interneurons located in lamina VII show firing behaviour consistent with a role in either rhythm generation or pattern formation, with the pPF dI6 cells preferentially situated laterally. As our hypothetically premotor pPF dI6 cells fire predominantly in phase with their local ventral root and we find little evidence to support an exclusively inhibitory nature, our results suggest that an excitatory population of dI6 interneurons may exist and thus further examination of the neurotransmitter phenotype is necessary. The present examination of spinal interneurons illuminates the manner in which the lumbar spinal cord is elegantly organized to execute the complex generation of locomotor activity.

• Subjects / Keywords

  • Spinal cord
  • Central pattern generator
  • DI6 interneuron population
  • Locomotion
  • V0 interneuron population

• Graduation date

  Fall 2016

• Type of Item

  Thesis

• Degree

  Doctor of Philosophy

• DOI

  https://doi.org/10.7939/R3639KG5W

• License

  This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.