We have been using optogenetics to understand the contributions of motoneuron activity to fictive locomotion in the neonatal mouse. For this purpose we have constructed mouse lines in which the excitatory channelrhodopsin or the inhibitory archaerhodopsin is expressed in motoneurons or in the spinal neurons that receive motoneuron inputs. Hyperpolarizing extensor motoneurons by exposure to light results in the neurons firing in the wrong, flexor phase of the cycle, because their membrane potential becomes lower than the chloride equilibrium potential thereby rendering rhythmic inhibitory input depolarizing. Whole cell voltage clamp experiments have revealed that some extensor motoneurons receive exclusively inhibitory rhythmic drive whereas some flexor motoneurons receive purely excitatory rhythmic drive. In motoneurons expressing the excitatory channelrhodopsin-2, we found that blue light could reset the locomotor rhythm consistent with these neurons having access to the central pattern generator. Traditionally, mammalian motoneurons have been thought to exhibit electrical connections only with members of the same motoneuron pool or close functional synergists. By contrast we have found that motoneurons in the L6 segments of the spinal cord are dye-coupled to non-cholinergic interneurons. Evidence that this motoneuron-interneuron network may be important functionally, and more extensive than the L6 segments comes, from the observation that spinal networks can generate synchronized rhythmic drive in the absence of chemical synaptic transmission. Bath-application of ruthenium red (RR) after blocking all chemical neurotransmission produces a slow bursting rhythm in motoneurons and interneurons that is synchronous ipsilaterally and contralaterally throughout the spinal cord.

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Blivis, Dvir; Haspel, Gal; Mannes, Philip Z et al. (2017) Identification of a novel spinal nociceptive-motor gate control for A? pain stimuli in rats. Elife 6:
Falgairolle, Melanie; Puhl, Joshua G; Pujala, Avinash et al. (2017) Motoneurons regulate the central pattern generator during drug-induced locomotor-like activity in the neonatal mouse. Elife 6:
Pujala, Avinash; Blivis, Dvir; O'Donovan, Michael J (2016) Interactions between Dorsal and Ventral Root Stimulation on the Generation of Locomotor-Like Activity in the Neonatal Mouse Spinal Cord. eNeuro 3:
Falgairolle, Melanie; O'Donovan, Michael J (2015) Pharmacological Investigation of Fluoro-Gold Entry into Spinal Neurons. PLoS One 10:e0131430
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Aliaga, Leonardo; Lai, Chen; Yu, Jia et al. (2013) Amyotrophic lateral sclerosis-related VAPB P56S mutation differentially affects the function and survival of corticospinal and spinal motor neurons. Hum Mol Genet 22:4293-305
Blivis, Dvir; O'Donovan, Michael J (2012) Retrograde loading of nerves, tracts, and spinal roots with fluorescent dyes. J Vis Exp :
Gonzalez-Islas, Carlos; Chub, Nikolai; Garcia-Bereguiain, Miguel Angel et al. (2010) GABAergic synaptic scaling in embryonic motoneurons is mediated by a shift in the chloride reversal potential. J Neurosci 30:13016-20

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