Nitric Oxide Potentiation of Locomotor Activity in the Spinal Cord of the Lamprey

Abstract

To understand the intrinsic operation of spinal networks generating locomotion, we need to not only characterize the constituent neurons and their connectivity, but also determine the role of intrinsic modulation in shaping the final motor output. We have focused on the effects of nitric oxide (NO) on the locomotor frequency and the underlying synaptic mechanisms in the lamprey spinal cord. To identify the source of NO, we used NADPH-diaphorase histochemistry and nNOS immunocytochemistry. Gray matter and sensory neurons were positively labeled using both methods. Preparations preincubated with NO synthase inhibitors displayed slower locomotor frequency that increased upon washout of the inhibitors, suggesting that NO is an endogenous neuromodulator in the spinal cord. Application of NO donors increased the locomotor frequency that was blocked by an NO scavenger and partially reduced by an inhibitor of sGC. To analyze the synaptic modulation underlying the NO-induced increase of the locomotor frequency we performed intracellular recordings from motoneurons and interneurons. The NO-induced increase in locomotor frequency was associated with a decrease in the midcycle inhibition and an increase in on-cycle excitation. To determine the site of action of NO, we examined the effect of NO donors on miniature PSCs. NO increased both the frequency and amplitude of mEPSCs while it only decreased the frequency of mIPSCs, suggesting the increased excitation is mediated by both presynaptic and postsynaptic mechanisms, while the decrease in inhibition involves only presynaptic mechanisms. Our results demonstrate a significant role of NO in adult vertebrate motor control which, via modulation of both excitatory and inhibitory transmission, increases the locomotor burst frequency.

Nitric Oxide Synthase Regulates Morphogenesis of Zebrafish Spinal Cord Motoneurons

“…Changes in tail beat frequency observed in DETA-NO/NOS1 AMO-treated fish most likely arise from an effect on firing of premotor circuitry. Although our anatomical studies show that primary interneuron morphogenesis is unaffected by NO, it remains possible that electrical and/or synaptic properties of spinal interneurons are modulated by this signaling molecule (McLean et al, 2001;McLean and Sillar, 2004;Kyriakatos et al, 2009). Future studies will help determine whether this is the case.…”

Pattern of Nitrergic Neuronal System Organization in the Brain of Two Holostean Fishes (Actinopterygii: Ginglymodi)

“…References: agnathans: Schober et al, 1994a;Kyriakatos et al, 2009;chondrichthyes: Shiells and Falk, 1992;Pérez et al, 1995;Álvarez-Otero et al, 1996;Funakoshi et al, 1997;Ferrando et al, 2012;Pose-Mendez et al, 2014;cladistians: López et al, 2016;chondrosteans: Pushchina and Obukhov, 2012;teleosts: Holmqvist et al, 1994teleosts: Holmqvist et al, , 2000Ostholm et al, 1994;Arévalo et al, 1995;Brüning et al, 1995;Anken and Rahmann, 1996;Cioni et al, 1997;Pottek et al, 1997;Funakoshi et al, 1999;Baby et al, 2000;Oyan et al, 2000;Haamedi and Djamgoz, 2002;Bordieri et al, 2003Bordieri et al, , 2005Singru et al, 2003;Ando et al, 2004;Bordieri and Cioni, 2004;Pushchina and Diuĭzen, 2004;Pushchina, 2007;Pushchina et al, 2007;Giráldez-Pérez et al, 2008Gaikwad et al, 2009;Pushchina and Obukhov, 2010;Ganz et al, 2012;lungfishes: Schober et al, 1994b;Northcutt, 2009;amphibians: Nöll et al, 1994;Crowe et al, 1995;Kurenni et al, 1995;Brüning and Mayer, 1996;González et al, 1996González et al, , 2002b…”

“…However, colocalization of NOS with ChAT in the spinal motoneurons is an unusual feature that has been described only in some species of teleosts Giráldez-Pérez et al, 2009] and mammals [Dun et al, 1992;Terenghi et al, 1993;Wetts and Vaughn, 1994]. However, the effect of NO in the regulation of the locomotor activity has been demonstrated in the lamprey spinal cord [Kyriakatos et al, 2009], and other functions for NO in the spinal cord are inhibition of the nociceptive information and pain control [Hervera et al, 2010;Chu et al, 2011;Cury et al, 2011;Jin et al, 2011Jin et al, , 2012.…”

Neuromodulation as a mechanism for the induction of repetition priming

“…VOc activity is tightly phase-locked to motor neuron activity during fictive locomotion [46]. Effects of nitric oxide (NO) on locomotor activity have also been demonstrated in the tadpole [47], lamprey [48, 49] and more recently in the mouse [50]. In the mouse and lamprey, nitric oxide effects are cGMP mediated [48, 50].…”