Excitatory Actions of Ventral Root Stimulation During Network Activity Generated by the Disinhibited Neonatal Mouse Spinal Cord

Abstract

To further understand the excitatory effects of motoneurons on spinal network function, we investigated the entrainment of disinhibited rhythms by ventral root (VR) stimulation in the neonatal mouse spinal cord. A brief train of stimuli applied to a VR triggered bursting reliably in 31/32 experiments. The same roots that entrained disinhibited bursting could also produce locomotor-like activity with a similar probability when the network was not disinhibited. The ability of VR stimulation to entrain the rhythm persisted in nicotinic and muscarinic cholinergic antagonists but was blocked by the AMPAR antagonist NBQX. Bath application of the type I mGluR1 receptor antagonist CPCCOEt reduced the ability of both dorsal root and VR stimulation to entrain the disinhibited rhythm and abolished the ability of either type of stimulation to evoke locomotor-like activity. Calcium imaging through the lateral aspect of the cord revealed that VR stimulation and spontaneously occurring bursts were accompanied by a wave of activity that originated ventrally and propagated dorsally. Imaging the cut transverse face of L(5) revealed that the earliest VR-evoked optical activity began ventrolaterally. The optical activity accompanying spontaneous bursts could originate ventrolaterally, ventromedially, or throughout the mediolateral extent of the ventral horn or very occasionally dorsally. Collectively, our data indicate that VR stimulation can entrain disinhibited spinal network activity and trigger locomotor-like activity through a mechanism dependent on activation of both ionotropic and metabotropic glutamate receptors. The effects of entrainment appear to be mediated by a ventrolaterally located network that is also active during spontaneously occurring bursts.

Sensory-Derived Glutamate Regulates Presynaptic Inhibitory Terminals in Mouse Spinal Cord

“…To further explore the function of presynaptic mGluR1β, we measured presynaptic inhibition physiologically in wt mice, using the in vitro spinal cord preparation, following bath application of the mGluR1 antagonist CPCCOEt (Bonnot et al, 2009). There was a trend towards a reduction in presynaptic inhibition, which did not reach statistical significance (Figure 6D), suggesting that the effect of pharmacological block of mGluR1 signaling on GAD67 requires longer duration exposure.…”

Current Principles of Motor Control, with Special Reference to Vertebrate Locomotion

“…In newborn rodent, antidromic stimulation of motoneuron via ventral roots can induce rhythmic locomotor-like activity (340) and entrain the spontaneous rhythmic activity induced (51). In neonate mouse, optogenetic manipulation of the activity of motoneurons during ongoing drug-induced locomotor activity also altered the frequency, phase, and stability of the rhythm (159).…”

Recurrent excitation between motoneurones propagates across segments and is purely glutamatergic

“…In neonatal animals, VR stimulation can induce fictive locomotion (Mentis et al, 2005) and 153 entrain the spontaneous rhythmic bursting induced by block of inhibition (Bonnot et al, 2009). 154 Furthermore, optogenetic activation or silencing of motor pools alters the frequency and phase 155 of chemically induced fictive locomotion (Falgairolle et al, 2017).…”

“…In neonatal animals VR stimulation can induce fictive locomotion (Mentis et al, 2005). These 10 effects cannot be explained solely by recurrent excitation and may provide evidence for Mn 11 collaterals contacting unidentified interneurones (Machacek and Hochman, 2006) connected 12 to the central pattern generator for locomotion (Bonnot et al, 2009). The recurrent excitation 13 characterised in the present study comprises predominantly a monosynaptic component evi-14 denced by the near constant latency of responses and extensive connectivity among Mn pairs.…”