Background

Historically, the in vitro spinal cord of neonatal rodent was developed to study the spinal reflexes (Otsuka and Konishi, 1974). In 1984, Suzue was the first to develop the in vitro brainstem-spinal cord preparation of newborn rat. Thus, it was possible to demonstrate that an isolated central nervous system was able to generate spontaneously what is referred as fictive respiratory activity. Later, it was then possible to determine the location of the CPGs underlying the locomotor rhythm generation (Cazalets et al., 1995; Kjaerulff and Kiehn, 1996; Ballion et al., 2001) and those engaged in respiratory rhythm generation (Smith et al., 1991; Onimaru and Homma, 2003). In our research team, this preparation has been mainly used to study the neural mechanisms underlying the interaction between CPGs. For instance, in a context of interaction between CPGs involved in the same function, our results have contributed to characterize the role played by the sensory afferents and the spinal thoracic segments in the coordination between the cervical and the lumbar locomotor CPGs (Juvin et al., 2005; 2012). Similarly, this preparation allows studies on the neural mechanisms involved in coordination between CPGs engaged in different functions. Based on electrical stimulation of dorsal roots, it was shown that the proprioceptive inputs originating from both hindlimb and forelimb are involved in the respiratory rhythm entrainment observed during locomotion (Morin and Viala, 2002; Giraudin et al., 2012). These ascending entraining signals from the cervical and lumbar afferents are conveyed to the brainstem respiratory centers via a brainstem pontine relay located in the parabrachial/Kölliker-Fuse complex (Giraudin et al., 2012). Using pharmacological and intracellular (patch-clamp recording) approaches on the same preparation, recent results have demonstrated for the first time the existence of an ascending pathway from the lumbar locomotor CPGs to the respiratory CPGs. This central neurogenic mechanism, involving a substance P-dependent modulating mechanism, could play a crucial role in the increased respiratory frequency observed during locomotion (Le Gal et al., 2014). In addition, it was also demonstrated that the locomotor related signal from the lumbar locomotor CPGs selectively modulates the intracellular activity of spinal expiratory neurons (Le Gal et al., 2016). Altogether, our results obtained on the in vitro brainstem spinal cord preparation of new born rat have contributed to increase our understanding of the cellular bases engaged in the coordination of rhythmic neural circuitry responsible for different functions.