The excitability of lumbar motoneurones in the neonatal rat is increased by a hyperpolarization of their voltage threshold for activation by descending serotonergic fibres

• Published in: The Journal of physiology 2004-07, Vol.558 (1), p.213-224
• Main Authors: Gilmore, Jonathan, Fedirchuk, Brent
• Format: Article
• Language: English
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Animals; Animals, Newborn; Brain Stem - cytology; Brain Stem - physiology; Electric Stimulation; Evoked Potentials, Motor - drug effects; Evoked Potentials, Motor - physiology; Ketanserin - pharmacology; Locomotion - physiology; Lumbar Vertebrae; Motor Neurons - physiology; Periodicity; Rats; Rats, Sprague-Dawley; Research Papers; Serotonin - physiology; Serotonin Antagonists - pharmacology; Spinal Nerve Roots - cytology; Spinal Nerve Roots - physiology
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2004.064717

Previous work has shown there is an increase in motoneurone excitability produced by hyperpolarization of the threshold potential at which an action potential is elicited ( V th ) at the onset, and throughout brainstem-induced fictive locomotion in the decerebrate cat. This represents a transient facilitation in the membrane potential for activation dependent on the presence of fictive locomotion. The present study tests the hypothesis that a similar neuromodulatory mechanism facilitating neuronal recruitment also exists in the neonatal rat, and the endogenous pathway mediating the V th hyperpolarization can be activated by electrical stimulation of the neonatal brainstem. Isolated brainstem–spinal cord preparations from 1- to 5-day-old neonatal rats, and whole-cell recording techniques were used to examine the patterns of ventral root (VR) activity produced, and the effect of electrical stimulation of the ventromedial medulla on lumbar spinal neurones. Hyperpolarization of V th was seen in 10/11 (range –2 to –18 mV) neurones recorded during locomotor-like VR activity, and appeared analogous to the locomotor-dependent V th hyperpolarization previously described in the cat. However, in the present study, V th hyperpolarization was also seen during electrical brainstem stimulation that evoked alternating, rhythmic, or tonic VR activity, or failed to evoke VR activity. Thirty-six of 71 neurones were antidromically identified as lumbar motoneurones and 33/36 showed a hyperpolarization of V th (–2 to –14 mV) during electrical brainstem stimulation. Of the unidentified lumbar ventral horn neurones, 31/35 also showed hyperpolarization of V th (–2 to –20 mV) during brainstem stimulation. The hyperpolarization of V th and VR activity induced by brainstem stimulation was reversibly blocked by cooling of the cervical cord, indicating it is mediated by descending fibres, and application of the serotonergic antagonist ketanserin to the spinal cord was effectively able to block the brainstem-evoked hyperpolarization of V th . These results demonstrate a previously unknown action of the endogenous descending serotonergic system to facilitate spinal motoneuronal recruitment and firing by inducing a hyperpolarization of V th . This modulatory process can be examined in the neonatal rat brainstem–spinal cord preparation without the requirement for ongoing locomotor activity.