B. carried out electrophysiological experiments; K.K. performed the purification of the exosomal fraction, immunoelectron microscopy of exosomes, and exosome uptake assays in myotubes from gastrula selleck inhibitor embryos and the CNS cell line; J.A. carried out electrophysiology and immunoelectron microscopy; M.Y. contributed to the initial observation of trans-synaptic Syt4 transfer,

generation of the chicken Syt4 antibody, and to helpful discussions; and V.B. directed the project, experimental design, and interpretations and wrote the manuscript. “
“Rhythm generation is a key feature of repetitive behaviors such as locomotion, mastication, and respiration. Two main concepts have been proposed to account for rhythmogenesis in central pattern generators (CPGs) (Marder and Bucher, 2001). The pacemaker concept relies on neurons that generate inherent rhythmic bursts of spikes when synaptic transmission is blocked. In contrast, the network hypothesis

suggests that the rhythm arises from nonlinear synaptic interactions. The specific contribution of cellular and network properties in generating rhythmic activities underlying locomotion are not understood. HA-1077 in vivo The persistent (slowly inactivating) sodium current (INaP) was suggested to play an important role in generating rhythmic motor behaviors ( Brocard et al., 2010; Butera et al., 1999; McCrea and Rybak, 2007; Pace et al., 2007; Paton et al., 2006; Rybak et al., 2006; Tazerart et al., 2007; Zhong et al., 2007), and INaP-dependent pacemaker properties may represent a common feature of CPGs ( those Brocard et al., 2006; Rybak et al., 2006; Tazerart et al.,

2008; Thoby-Brisson and Ramirez, 2001; Ziskind-Conhaim et al., 2008). Importantly, blockade of INaP by riluzole abolishes locomotor-like activity in rodents ( Brocard et al., 2010; Tazerart et al., 2007; Zhong et al., 2007). In newborn rodents, interneurons considered to be elements of the motor CPGs express intrinsic riluzole-sensitive bursting properties when removing extracellular calcium (Brocard et al., 2006; Tazerart et al., 2008). Concomitantly, INaP was increased and its activation threshold was shifted toward more negative voltages ( Tazerart et al., 2008). Such properties observed in nonphysiological conditions (zero calcium) raise the question of their functional relevance to the normally operating network. Although changes in the ionic concentration of the extracellular space are usually not considered as relevant physiological signals, the locomotor activity was shown to increase the extracellular concentration of potassium ([K+]o) in the spinal cord ( Marchetti et al., 2001; Wallén et al., 1984). While the precise dynamic changes in [K+]o during locomotion remain to be determined, no attention has been paid to the possibility that changes in the extracellular calcium concentration ([Ca2+]o) might regulate the firing properties of spinal CPG interneurons.