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Regulation of the motor output of the spinal cord: burst firing generation and sensorimotor integration

Mahrous, Amr A.
http://orcid.org/0000-0001-9027-1960
http://rave.ohiolink.edu/etdc/view?acc_num=wright1523970444739026

Abstract Details

2018, Doctor of Philosophy (PhD), Wright State University, Biomedical Sciences PhD.
Spinal motoneurons are the final common path for motor signals. Thus, the firing activity recorded from spinal motoneurons or their axons in the ventral roots represents the motor output of the nervous system. This dissertation investigates two major phenomena that help generate and shape the neuronal motor output. Specialized groups of spinal neurons called central pattern generators (CPGs) are capable of orchestrating rhythmic bursting activity without involvement of the brain. This activity underlies stereotyped movements such as locomotion. If known, the ionic mechanisms responsible for generating this activity can offer new pharmacological interventions to restore walking in paralyzed patients with intact spinal circuits. In part-I of this dissertation, we examined the role of the small conductance Ca2+-activated potassium (SK) channels in the generation of rhythmic activity. SK channels represent a strong candidate for controlling bursting behaviors because they have a dual regulatory function on both the synaptic inputs and the firing output of spinal neurons. Rhythmic activity was studied in murine spinal cord preparations in vitro using intracellular and extracellular electrophysiological recordings. The data showed that inhibition of SK channels -using multiple approaches- facilitates the initiation of rhythmic motor outputs. Additionally, graded pharmacological modulation of SK channels determined the amplitude of the motor bursts in a dose-dependent manner. Similar manipulations of other types of ion channels did not replicate these effects. The autonomous activity of the spinal CPGs can continue for long periods of time without extrinsic inputs. However, to meet the demands of the environment, the locomotor activity has to undergo continuous modulation by peripheral sensory inputs and descending supraspinal inputs (sensorimotor integration). These synaptic inputs exhibit use-dependent plasticity at physiological firing frequencies (either facilitation or depression). Using a combination of intracellular and extracellular recordings, part-II of this dissertation investigated how variable sensory and descending inputs of different frequencies, amplitudes, and neuromodulatory states generate a steady motor output at the cellular and system levels. The data indicated that integration of multiple, despite adapting, excitatory inputs help generate a stable motor output by maintaining the synaptic potentials above the firing threshold, which was more readily achievable at higher neuromodulatory states.
Sherif Elbasiouny, Ph.D. (Advisor)
Mark Rich, M.D., Ph.D. (Committee Member)
Mill Miller, Ph.D. (Committee Member)
David Ladle, Ph.D. (Committee Member)
Lynn Hartzler, Ph.D. (Committee Member)
168 p.
Biomedical Research; Cellular Biology; Neurosciences; Physiology
Spinal Cord; Motoneurons; Motor Output; Rhythmic Activity; Neuronal Bursting; Fictive Locomotion; SK Channels; Apamin; Methoxamine; Synaptic Plasticity; Sensorimotor Integration; Synaptic Integration; Neuromodulatory State

Recommended Citations

Citations

  • Mahrous, A. A. (2018). Regulation of the motor output of the spinal cord: burst firing generation and sensorimotor integration [Doctoral dissertation, Wright State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=wright1523970444739026

    APA Style (7th edition)

  • Mahrous, Amr. Regulation of the motor output of the spinal cord: burst firing generation and sensorimotor integration. 2018. Wright State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=wright1523970444739026.

    MLA Style (8th edition)

  • Mahrous, Amr. "Regulation of the motor output of the spinal cord: burst firing generation and sensorimotor integration." Doctoral dissertation, Wright State University, 2018. http://rave.ohiolink.edu/etdc/view?acc_num=wright1523970444739026

    Chicago Manual of Style (17th edition)

wright1523970444739026
271
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This open access ETD is published by Wright State University and OhioLINK.