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Postnatal development of the lumbar spinal circuitry in the presence and absence of descending systems

Smith, Calvin Chad (2016) Postnatal development of the lumbar spinal circuitry in the presence and absence of descending systems. PhD thesis, University of Leeds.

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Motor maturity in the rat is achieved 3 weeks after birth. Significant reorganisation and refinement of spinal and supraspinal systems contribute to acquisition of this mature behaviour; however the process remains poorly characterised. For example, descending innervation of the spinal circuitry is weak at birth and the extent to which developing supraspinal projections guide maturation of spinal circuits is not known. To address these questions, the present study developed an in-situ, perfused whole rat preparation in which the development of motor control can be studied throughout the postnatal (PN) period. Using electrophysiological and immunohistochemistry techniques, we tracked the PN development of muscle afferents and their modulation in the lumbar spinal cord. Inputs to motoneurons (MNs) from premotor interneurons were also assessed. To establish the dependence of lumbar spinal circuit organisation on descending systems, we conducted the same assessments on rats spinalised (mid-thoracic) at postnatal day 5 (PN5 TX). Results show that Ia afferent innervation of the lumbar cord is widespread early PN and retracted with development. PN5 TX abolished this retraction, with greater densities of afferents found at PN14 and 21 compared to intact controls. This leads to reduced H-reflex thresholds and increased H max/M max ratios in our novel preparation, suggesting hyperexcitability of the lumbar spinal circuitry following PN5 TX. We conduct the first assessments of developmental innervation of Ia afferents by GABApre neurons (P boutons), which modulate afferent firing. This revealed that P bouton density was low early in development and increased PN, a process which is severely attenuated by PN5 TX. This was likely responsible for reduced paired pulse depression of the H-reflex in PN5 TX rats. In general, premotor inputs to MNs were retracted throughout development and PN5 TX did not significantly disrupt this profile. Our results suggest developmental competition between afferent and descending systems for synaptic coverage of spinal circuits, with PN5 TX removing descending competition and preventing normal PN retraction of afferents. This, in conjunction with reduced presynaptic inhibition significantly increases excitability of the lumbar spinal circuitry. These results provide a greater understanding of the neural mechanisms responsible for PN acquisition of mature motor control and bear important implications for further study of conditions such as cerebral palsy and spinal cord injury.

Item Type: Thesis (PhD)
Academic Units: The University of Leeds > Faculty of Biological Sciences (Leeds)
The University of Leeds > Faculty of Biological Sciences (Leeds) > Institute of Membrane and Systems Biology (Leeds)
Identification Number/EthosID: uk.bl.ethos.689287
Depositing User: Mr Calvin Chad Smith
Date Deposited: 05 Jul 2016 14:04
Last Modified: 18 Feb 2020 12:31
URI: http://etheses.whiterose.ac.uk/id/eprint/13464

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