Orexinergic Modulation of Spinal Motor Activity in the Neonatal Mouse Spinal Cord.

Sukanya Biswabharati,Adam P Lognon,Rhiannon Brett,Louisa Hardjasa,Céline Jean-Xavier,Patrick J Whelan,Shane E A Eaton

doi:10.1523/eneuro.0226-18.2018

Abstract

The role of orexin during development, and especially in terms of spinal cord function, is not well understood. It is for this reason that we focused on the network actions of orexin during the first week of development. We found that orexinergic fibers were present in the lumbar spinal cord of postnatal day 0 (P0) to P3 mice. The fibers were expressed mainly in the dorsal horn, but occasional fibers were observed in the ventral horn. Both orexin (OX) A and OXB increased the motoneurons (MNs) tonic neurogram discharge. However, only OXA was found to significantly increase spontaneous bursting activity and the frequency of fictive locomotor bursts. We show that OXA is able to act directly on MNs. To test the contribution of the recurrent MN collaterals, we blocked the nicotinic cholinergic drive and observed that OXA retained its ability to increase fictive locomotor activity. Additionally, we recorded neurograms from ventral lateral funiculi, where OXA had no effect on population discharge. These effects were also confirmed by recording from descending commissural interneurons via patch recordings. The loci of the effects of OXA were further investigated in a dorsal horn-removed preparation where OXA also shows an increase in the discharge from ventral root neurograms but no increase in the frequency of spontaneous or fictive locomotion burst activity. In summary, multiple lines of evidence from our work demonstrate the robust effects of orexins on spinal cord networks and MNs at the time of birth.

Highlights

Orexin (OX) neuropeptides were discovered in 1998 and consist of OXA and OXB
We found that OX-IRϩ could be observed in the lateral white matter, along the lateral funiculus of the spinal cord and within the spinal cord (P3; Fig. 1A, v, C, iii)
Recording from ventral roots shows that when fast neurotransmitter blockers are applied, OXA strongly increases activity in AC and in DC recordings, reflecting population recordings of presumptive MNs leading to a sustained bursting discharge in the neurograms

Summary

Introduction

Orexin (OX) neuropeptides were discovered in 1998 and consist of OXA and OXB (de Lecea et al, 1998; Sakurai et al, 1998). OXergic neurons are confined to the lateral hypothalamus (LH), an area associated with a variety of goal-directed actions, including locomotor initiation (Li et al, 2014; Sakurai, 2014). OX modulates excitatory and inhibitory actions on neurons through G-protein-coupled. The authors declare no competing financial interests. S.B., C.J.-X., S.E.A.E., A.P.L., R.B., and L.H. performed research; S.B., C.J.-X., S.E.A.E., A.P.L., R.B., and L.H. analyzed data; S.B., C.J.-X., S.E.A.E., and. We thank Jillian Ejdrygiewicz, Claude Veillette, and Michelle Tran for technical assistance

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