Neurokinin Receptor-Expressing Pre-Bötzinger Complex Neurons in Neonatal Mice Studied In Vitro

Abstract

Hayes JA, Del Negro CA. Neurokinin receptor-expressing preBötzinger complex neurons in neonatal mice studied in vitro. J Neurophysiol 97: 4215-4224, 2007. First published April 4, 2007 doi:10.1152/jn.00228.2007. Breathing in mammals depends on inspiratory-related neural activity generated in the pre-Bötzinger complex (preBötC), where neurokinin receptor-expressing neurons (NKR ϩ ) have been hypothesized to play a critical rhythmogenic role. Currently, the extent to which the preBötC is populated by rhythmogenic NKR ϩ neurons and whether neurons without neurokinin receptor expression (NKR Ϫ ) share similar electrical properties with NKR ϩ neurons are not well understood. These interrelated problems must be resolved to understand the widespread excitatory effects of neuropeptides and the mechanism of respiratory rhythmogenesis. We recorded and imaged inspiratory neurons in neonatal mouse slices that isolate the preBötC and generate respiratory motor output in vitro. Using tetramethylrhodamine conjugated to the endogenous NKR agonist substance P (TMR-SP) to tag neurons that express NKRs, we show that early inspiratory neurons with small whole cell capacitance (C M ) are 36% TMR-SP ϩ and 64% TMR-SP Ϫ . Also, late inspiratory neurons with large C M are 67% TMR-SP ϩ and 33% are TMR-SP Ϫ . Thus NKR ϩ and NKR Ϫ neurons exhibit the same phenotypic properties, which suggests that they may share functional roles also. Substance P (SP) alone evoked a voltage-insensitive inward current (I SP ) that reversed at -19 mV and was associated with an increase in membrane conductance in both NKR ϩ and NKR Ϫ neurons. Gap junctions may be needed to confer SP sensitivity to neurons that appear to lack NKR expression. We propose that cell death in NKR ϩ preBötC neurons, by targeted lesion or neurodegeneration, may impair breathing behavior by killing less than one half of the rhythmogenic preBötC neurons and a large number of respiratory premotoneurons.

Necdin Plays a Role in the Serotonergic Modulation of the Mouse Respiratory Network: Implication for Prader-Willi Syndrome

“…Effectively, the RRG of Ndn-KO functions and may even produce a stable rhythm under 5-HT. The rodent RRG is located within the RVLM, where neurons of the pFRG and the pre-Bötzinger complex play key roles in rhythmogenesis (Smith et al, 1991;Rekling and Feldman, 1998;Gray et al, 2001;Manzke et al, 2003;Onimaru and Homma, 2003;Hayes and Del Negro, 2007). In the RVLM, Necdin transcript is detected, but very few or any neurons of the preBötzinger complex and pFRG areas, respectively, express Necdin protein, whereas all 5-HT neurons do.…”

Opioids prolong and anoxia shortens delay between onset of preinspiratory (pFRG) and inspiratory (preBötC) network bursting in newborn rat brainstems

“…Identification of a putative pFRG kernel in newborn rats is, for example, hampered by the fact that the area between the VII nucleus and the preBötC contains respiratory networks that may correspond to the Bötzinger complex (BötC) in adults that is characterized by an abundance of expiratory neurons [19,53,58]. Moreover, this area also contains inspiratory neurons plus the retrotrapezoid nucleus (RTN) and other chemosensitive neural circuits that presumably influence the respiratory networks [19,23,62]. In fact, it has been hypothesized that the chemosensitive neonatal pFRG might be identical with the RTN in adults [18,19,42].…”

Identification of neurotransmitters and co-localization of transmitters in brainstem respiratory neurons

“…There are other cell types within the preBötC, not quite so widely studied as the small NK1-R neurons, including e.g., non-NK1-R neurons with either early or late inspiratory activity (Hayes and Del Negro, 2007) and respiratory neurons whose activity is modified by BDNF through the tyrosine kinase B (TrkB) receptor (Thoby-Brisson et al, 2003). A variety of neuronal phenotypes have also been identified by strictly anatomical methods (no evidence that they are respiratory other than location within the preBötC) that contain a variety of substances and receptors, either with or without NK1-R immunoreactivity (Liu et al, 2001; Liu and Wong-Riley, 2002; Liu et al, 2002, 2004, 2005).…”