Modulation of SK channels regulates locomotor alternating bursting activity in the functionally-mature spinal cord

ABSTRACT

The spinal cord contains specialized groups of cells called pattern generators, which are capable of orchestrating rhythmic firing activity in an isolated preparation. Different patterns of activity could be generated in vitro including right-left alternating bursting and bursting in which both sides are synchronized. The cellular and network mechanisms that enable these behaviors are not fully understood. We have recently shown that Ca²⁺-activated K⁺ channels (SK channels) control the initiation and amplitude of synchronized bursting in the spinal cord. It is unclear, however, whether SK channels play a similar role in the alternating rhythmic pattern. In the current study, we used a spinal cord preparation from functionally mature mice capable of weight bearing and walking. The present results extend our previous work and show that SK channel inhibition initiates and modulates the amplitude of alternating bursting. We also show that addition of methoxamine, an α₁-adrenergic agonist, to a cocktail of serotonin, dopamine, and NMDA evokes robust and consistent alternating bursting throughout the cord.

KEYWORDS:

• fictive locomotion
• SK channels
• neuronal bursting
• spinal motoneurons
• methoxamine

Disclosure

The authors declare no competing financial interests.

Acknowledgment

Funding to this work was provided by NINDS-NIH (grant # NS091836) for S.E.; A.M. was supported by the Biomedical Sciences PhD Program at Wright State University.