Lumbar spinal cord excitability: flexors vs. extensors, sensitivity to quipazine; effects of activity following spinal transection; and expression of post-synaptic serotonin receptors

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2013-01-30, 2014-04-04
Chopek, Jeremy W.
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American Physiological Society
Mary Ann Liebert Inc. Publisher
Serotonin (5-HT) is a well-known modulator of spinal cord excitability and motor output. In the spinal cord, the actions of 5-HT are primarily mediated by the 5-HT1AR, 5-HT2Rs and the 5-HT7R. Following a spinal cord transection, which results in a loss of supraspinal input, 5-HT agonists such as quipazine are used to provide excitation to the spinal cord to facilitate locomotor recovery. This is characterized by rhythmic alteration of left and right hindlimbs and ipsilateral flexor and extensor muscles. However, whether 5-HT has a global effect on spinal cord excitability or is confined to a specific motor group (i.e. flexors or extensors) is currently unknown. Furthermore, quipazine is used in conjunction with activity based interventions to enhance recovery following a spinal cord injury. However, the influence of limb activity on the responsiveness of the injured spinal cord to quipazine has not been examined. Lastly, the recovery of locomotion is at least in part thought to occur through an up-regulation of 5-HT receptors, although this has not been investigated in lumbar spinal cord. Chapter 2 examines whether quipazine had a differential effect on flexor and extensor motor output assessed by recording flexor and extensor reflexes, motoneurons and Ia extracellular field potentials pre- and post-quipazine. It was determined that following an acute spinal transection, quipazine induced a larger flexor monosynaptic reflex (MSR) compared to the extensor MSR due to pre-synaptic but not motoneuron modulation. Chapter 3 examines the influence of a chronic spinal transection with and without passive cycling on the hindlimb flexor and extensor MSR, both pre- and post-quipazine. It was found that three months post STx, the extensor but not flexor MSR demonstrated a hyperexcitable response, which was attenuated with passive cycling. Further, three months of passive cycling extensor MSR response to quipazine was similar to that seen in the control intact group. Chapter 4 examined 5-HT receptor expression in flexor and extensor motoneurons three months post spinalization with or without passive cycling. Following a chronic STx, the 5-HT1AR and 5-HT2CR are down regulated, whereas the 5-HT2AR is up-regulated. Passive cycling further enhanced the 5-HT2AR expression as well as up-regulated the 5-HT7R in extensor but not flexor motoneurons. Chapter 5 discusses the results and significance of these findings in detail.
serotonin, motoneuron, spinal reflexes, exercise
Chopek JW, MacDonell CW, Power KE, Gardiner K, Gardiner PF, (2013). Removal of supraspinal input reveals a difference in the flexor and extensor monosynaptic reflex response to quipazine independent of motoneuron excitation. Journal of Neurophysiology 109: 2056-206.
Chopek JW, MacDonell CW, Gardiner K, Gardiner PF (2014). Daily passive cycling attenuates the hyperexcitability and restores the responsiveness of the extensor monosynaptic reflex to quipazine in the chronic spinal transected rat. Journal of neurotrauma 31: 1083-7.