Evidence of intermediate reticular formation involvement in swallow pattern generation, recorded optically in the neonate rat sagittally sectioned hindbrain

Abstract

Swallow is a primitive behavior regulated by medullary networks, responsible for movement of food/liquid from the oral cavity to the esophagus. To investigate how functionally heterogeneous networks along the medullary intermediate reticular formation (IRt) and ventral respiratory column (VRC) control swallow, we electrically stimulated the nucleus tractus solitarius to induce fictive swallow between inspiratory bursts, with concurrent optical recordings using a synthetic Ca2+ indicator in the sagittally-sectioned rat hindbrain preparation (SSRH). Simultaneous recordings from hypoglossal nerve rootlet (XIIn) and ventral cervical spinal root C1-C2 enabled identification of the system-level correlates of A) swallow (identified as activation of the XIIn but not the cervical root), and B) Breuer-Hering expiratory reflex (BHE: lengthened E in response to stimuli during E). Optical recording revealed reconfiguration of respiration-modulated networks in the ventrolateral medulla during swallow and the BHE reflex. Recordings identified novel spatially compact networks in the IRt near the facial nucleus (VIIn) that were active during fictive swallow, suggesting that the swallow network is not restricted to the caudal medulla. These findings also establish the utility of using this in vitro preparation to investigate how functionally heterogeneous medullary networks interact and reconfigure to enable a repertoire of orofacial behaviors.

Postinspiratory complex acts as a gating mechanism regulating swallow-breathing coordination and other laryngeal behaviors

“…Diaphragm activity has been shown to be multimodal, having different activity patterns for swallow and breathing, including concurrent inhibited respiratory related activity and activated swallow related activity, Schluckatmung , in physiologic and fictive swallows (Huff et al, 2022; Pitts et al, 2021; Pitts et al, 2018). Activation of glutamatergic neurons in the area of PiCo resulted in swallow related diaphragmatic activation, Schluckatmung .…”

“…It has been hypothesized that the SPG activates pre-motor neurons in the dorsal respiratory group responsible for diaphragm recruitment during swallow (Pitts et al, 2018). Inspiratory neurons of the medial reticular formation have been shown to increase firing frequency during Schluckatmung (Pitts et al, 2021).…”

“…It was hypothesized this complex may be involved in various postinspiratory behaviors such as swallowing and vocalization (Anderson et al, 2016). Since, work in the rodent has shown this region serves as a premotor relay within the IRt that integrates postinspiratory motor outputs and other non-respiratory central pattern generators (CPGs) such as swallowing, crying, lapping, whisking (Ain Summan Toor et al, 2019; Dempsey et al, 2021; Moore et al, 2013; Moore, Kleinfeld, & Wang, 2014; Pitts, Huff, Reed, Iceman, & Mellen, 2021), suggesting that PiCo may serve as a hub, acting as a gate, for various laryngeal postinspiratory behaviors.…”

Synchronization of inspiratory burst onset along the ventral respiratory column in the neonate mouse is mediated by electrotonic coupling

“…To assess whether they might coordinate the observed distributed initiation of inspiratory bursts, a broad-spectrum synaptic blocker cocktail was applied, silencing respiratory motor output within 2 min of drug application. Patency of blockade was validated by showing that following synaptic blockade, post-synaptic networks mediating swallow were no longer activated by stimulation of putative command networks for swallow in dorsomedial medulla [ 19 ] (Video in Additional file 5 ).…”

Advances in Swallowing Neurophysiology Across Pediatric Development: Current Evidence and Insights

“…These brainstem networks are considered critical correlates of the developing neural swallowing control. Recently, Pitts and colleagues [2021] used an in vitro neonatal rat model to examine the role of the swallow CPG, as well as additional areas in the medulla (specifically, the medullary intermediate reticular formation (IRt) and the ventral respiratory column (VRC)), in eliciting cranial nerve responses indicative of a fictive swallow and/or a breathing reflex [44]. Critically, they found that, in addition to neurons within the swallow CPG, new networks within the IRt, near the facial nucleus in the dorsal medulla, were also active during the swallows.…”