An investigation of the role of the intraspinal cholinergic system in the modulation of motoneuron voltage threshold
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Date
2016
Authors
Vasquez-Dominguez, Edna Esteli
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Abstract
Previous work has demonstrated that rhythmic motor outputs, such as locomotion and scratch induce a hyperpolarization of the voltage threshold (Vth) for action potential initiation in spinal motoneurons, enhancing their excitability. Descending monoamines were implicated in mediating this effect; however, the recent observation that changes in Vth persist during fictive scratch in cats following acute cervical transection revealed that intraspinal systems, of unknown neuromodulatory identity, also have the ability to regulate motoneuron excitability during motor behaviour. This thesis addresses: 1) whether acetylcholine (ACh) is able to modulate spinal motoneuron Vth, and 2) whether endogenous ACh modulates motoneuron excitability during motor activity without intact descending modulation.
Our first study investigates whether ACh from exogenous and/or endogenous sources alters motoneuron Vth. We made intracellular recordings of lumbar motoneurons from neonatal rats to pharmacologically manipulate muscarinic and nicotinic receptor activity. Results show that ACh induces either Vth hyperpolarization, Vth depolarization or no change in Vth depending on the activity state of the network, the ACh concentration, and influences from other systems.
Our second study investigates whether intraspinal cholinergic inputs induce Vth hyperpolarization during rhythmic motor output when descending projections are disrupted. For this we developed an in vitro neonatal rat spinal cord preparation to elicit rhythmic activity independently of brainstem or lumbar cord stimulation. Intracellular recordings from motoneurons allowed comparison of the Vth prior to and during rhythmic output, both in the absence and presence of cholinergic antagonists in the lumbar cord. Results show that intraspinal cholinergic mechanisms are active and importantly contribute to modulation of motoneuron Vth during motor output.
We suggest that in addition to descending modulation, the spinal cholinergic system regulates motoneuron Vth to either facilitate or inhibit recruitment according to the motor network state. Motoneuron excitability regulation by modification of distinct membrane properties resulting from separate modulatory systems activation during diverse motor behaviours is discussed.
This work is the first to demonstrate the role of cholinergic mechanisms in regulating motoneuron excitability through modulation of Vth in an activity based context, and therefore outlines a spinal modulatory system that would contribute to motor control in both normal and pathological states.
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Keywords
Spinal cord, Motoneuron, Neuromodulation, Neurophysiology