Neurons in the Intermediate Reticular Nucleus Coordinate Postinspiratory Activity, Swallowing, and Respiratory-Sympathetic Coupling in the Rat

Abstract

Breathing results from sequential recruitment of muscles in the expiratory, inspiratory, and postinspiratory (post-I) phases of the respiratory cycle. Here we investigate whether neurons in the medullary intermediate reticular nucleus (IRt) are components of a central pattern generator (CPG) that generates post-I activity in laryngeal adductors and vasomotor sympathetic nerves and interacts with other members of the central respiratory network to terminate inspiration. We first identified the region of the (male) rat IRt that contains the highest density of lightly cholinergic neurons, many of which are glutamatergic, which aligns well with the putative postinspiratory complex in the mouse (Anderson et al., 2016). Acute bilateral inhibition of this region reduced the amplitudes of post-I vagal and sympathetic nerve activities. However, although associated with reduced expiratory duration and increased respiratory frequency, IRt inhibition did not affect inspiratory duration or abolish the recruitment of post-I activity during acute hypoxemia as predicted. Rather than representing an independent CPG for post-I activity, we hypothesized that IRt neurons may instead function as a relay that distributes post-I activity generated elsewhere, and wondered whether they could be a site of integration for para-respiratory CPGs that drive the same outputs. Consistent with this idea, IRt inhibition blocked rhythmic motor and autonomic components of fictive swallow but not swallow-related apnea. Our data support a role for IRt neurons in the transmission of post-I and swallowing activity to motor and sympathetic outputs, but suggest that other mechanisms also contribute to the generation of post-I activity.

PreBötzinger complex neurons drive respiratory modulation of blood pressure and heart rate

“…This effect on SNA is delayed compared to the latencies of responses recorded in VNA, and cannot be attributed to the relatively slow conduction velocity of sympathetic pathways, as SNA responses to photostimulation of sympathetic premotor neurons are also lower than those seen here ( Abbott et al, 2009 ; Menuet et al, 2014 ). These observations are consistent with a polysynaptic pathway prior to the recorded SNA, which could potentially include recruitment of neurons in the intermediate reticular nucleus ( Toor et al, 2019 ). Also, inhibitory, GABAergic CVLM neurons are respiratory modulated ( Mandel and Schreihofer, 2006 ) and could mediate inspiratory modulation of RVLM pre-sympathetic neurons arising from inhibitory or excitatory inspiratory preBötC neurons.…”

“…Single-pulse preBötC photoinhibition had no effect on RespSNA when applied during post-inspiration ( Figure 7 ). Part of the post-inspiratory component of RespSNA originates from post-inspiratory neurons in the intermediate reticular nucleus ( Toor et al, 2019 ), and similarly to RSA, the dorsolateral pons could also be involved ( Baekey et al, 2008 ; Dick et al, 2009 ). Indeed, ponto-medullary transections strongly decreased RespSNA and Traube-Hering waves.…”

The post‐inspiratory complex (PiCo), what is the evidence?

“…r ChAT-positive IRt neurons that overlap with the PiCo are involved in swallowing (Toor et al 2019). The Toor paper shows that inhibition of the IRt/PiCo neurons by isoguvacine removes PI activity from the VNA under resting conditions, similar to what has been shown with somatostatin and DAMGO by Anderson et al (2016).…”

Activation of μ-opioid receptors differentially affects the preBötzinger Complex and neighbouring regions of the respiratory network in the adult rabbit

“…In this context, it should be mentioned that evidence has been provided in the mouse that a medullary neural network, named post-inspiratory complex, generates post-inspiratory activity and is highly responsive to the activation of MORs (Anderson et al, 2016;Anderson and Ramirez, 2017). However, Toor et al (2019) have recently provided data showing that the intermediate reticular nucleus of the rat, that corresponds well neuroanatomically and phenotypically to the mouse post-inspiratory complex, contributes to the post-inspiratory activity, but is not required for termination of inspiration or recruitment of post-inspiratory activity during acute hypoxemia. They suggested that this neuronal population may not represent a distinct central pattern generator for post-inspiratory activity, but instead may operate as a relay that distributes post-inspiratory activity generated elsewhere.…”