Somatic Proximity of the Axon Initial Segment Predicts Motoneuron Excitability

Rotterman, Travis M.; Carrasco, Darío I.; Housley, Nick; Nardelli, Paul; Powers, Randy; Cope, Timothy C.

doi:10.21203/rs.3.rs-318156/v1

Cited by 1 publication

(1 citation statement)

References 56 publications

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“…Other channels, including KV1.2 channels, which underlie the characteristic delayed firing behaviour of fast motoneurons 24,27,28 , are also clustered at the AIS and may dynamically interact with NaV1.6 channels to shape recruitment current. Furthermore, given that the AIS is further from the soma in fast compared to slow motoneurons 95 , physical properties of the AIS may also contribute to differential recruitment of motoneuron subtypes. If so, one might predict that the distance between soma and AIS may increase in fast motoneurons during the first two postnatal weeks and contribute to functional specification of motoneuron subtypes.…”

Section: Discussionmentioning

confidence: 99%

Maturation of persistent and hyperpolarization-activated inward currents shapes the differential activation of motoneuron subtypes during postnatal development

Sharples

Miles

2021

Preprint

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The fine control of movement is a prerequisite for complex behaviour and is mediated by the orderly recruitment of motor units composed of slow and fast twitch muscle fibres. The size principle was initially proposed to account for orderly recruitment; however, motoneuron size is a poor predictor of recruitment amongst functionally defined motor unit subtypes. While intrinsic properties of motoneurons are key regulators of motoneuron recruitment, the underlying currents involved are not well defined. Whole-cell patch-clamp electrophysiology was deployed to study intrinsic properties, and the underlying currents, that contribute to the differential recruitment of fast and slow motoneurons. Motoneurons were studied during the first three postnatal weeks in mice to identify key properties that establish orderly recruitment and contribute to the emergence of fine motor control. We find that fast and slow motoneurons are functionally homogeneous during the first postnatal week and are recruited based on size, irrespective of motoneuron subtype. The recruitment of fast and slow motoneurons becomes staggered during the second postnatal week due to the differential maturation of passive and active properties, particularly persistent inward currents (PICs). The current required to recruit fast motoneurons increases further in the third postnatal week, despite no additional changes in passive properties or PICs. This further staggering of recruitment currents reflects development of a hyperpolarization-activated inward current during week 3. Our results suggest that motoneuron recruitment is multifactorial, with recruitment order established during postnatal development through the differential maturation of passive properties and sequential integration of persistent and hyperpolarization-activated inward currents.

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