Abstract
All behaviors require coordinated activation of motoneurons from central command and premotor networks. The genetic identities of premotoneurons providing behaviorally relevant excitation to any pool of respiratory motoneurons remain unknown. Recently, we established in vitro that Dbx1-derived pre-Bötzinger complex neurons are critical for rhythm generation and that a subpopulation serves a premotor function (Wang et al., 2014). Here, we further show that a subpopulation of Dbx1-derived intermediate reticular (IRt) neurons are rhythmically active during inspiration and project to the hypoglossal (XII) nucleus that contains motoneurons important for maintaining airway patency. Laser ablation of Dbx1 IRt neurons, 57% of which are glutamatergic, decreased ipsilateral inspiratory motor output without affecting frequency. We conclude that a subset of Dbx1 IRt neurons is a source of premotor excitatory drive, contributing to the inspiratory behavior of XII motoneurons, as well as a key component of the airway control network whose dysfunction contributes to sleep apnea.
Highlights
Understanding the genetic basis of behavior is a fundamental goal of neuroscience that requires functional identification of constituent neurons, knowledge of their embryonic origins, and characterization of their cellular, synaptic and modulatory properties (Goulding, 2009; GarciaCampmany et al, 2010)
XII premotoneurons are predominantly located in the intermediate medullary reticular formation (IRt) (Ono et al, 1994; Dobbins and Feldman, 1995; Woch et al, 2000; Peever et al, 2002; Koizumi et al, 2008; Stanek et al, 2014), a heterogeneous region that contributes to orofacial behaviors (Gestreau et al, 2005; Moore et al, 2013; Kleinfeld et al, 2014; Moore et al, 2014)
To measure the percentage of glutamatergic Dbx1 IRt neurons we used in situ hybridization to identify vesicular glutamate transporter 2 (VGlut2, coded by the Slc17a6 gene) in Dbx1lacZ reporter mice
Summary
Understanding the genetic basis of behavior is a fundamental goal of neuroscience that requires functional identification of constituent neurons, knowledge of their embryonic origins, and characterization of their cellular, synaptic and modulatory properties (Goulding, 2009; GarciaCampmany et al, 2010). The efferent motor network controlling inspiratory activity of tongue protruder muscles maintains airway patency and is an integral part of breathing behavior. This network minimally comprises the rhythmogenic pre-Botzinger Complex (preBotC), XII motoneurons that drive tongue protruder muscles, and inspiratory premotoneurons intercalated between the two (Koizumi et al, 2008; Fregosi, 2011) (Figure 1A). The IRt contains Dbx1-derived neurons (Gray, 2008, 2013; Ruangkittisakul et al, 2014) and diffusely distributed XII inspiratory premotoneurons (Koizumi et al, 2008). Because Dbx progenitors are a source of glutamatergic IRt neurons (Gray, 2008, 2013; Ruangkittisakul et al, 2014) and inspiratory motor drive is glutamatergic
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