Phenotypic traits of the hypothalamic PVN cells innervating airway-related vagal preganglionic neurons

Abstract

The paraventricular nucleus of the hypothalamus (PVN) integrates multiple inputs via projections from arginine vasopressin (AVP)- and oxytocin (OXT)-containing neurons to the brain stem and spinal cord as well as regulates respiratory and cardiovascular stress-related responses, which also affect airway function. In the present study, we used immunocytochemistry and the retrograde transneuronal tracer, Bartha strain of pseudorabies virus expressing green fluorescent protein (PRV-GFP), to localize AVP- and OXT-producing neurons that project to airway-related vagal preganglionic neurons (AVPNs) innervating intrapulmonary airways. PRV-GFP was microinjected into the upper right lung lobe, and after 4 days survival, hypothalamic tissue sections were processed for co-expression of PRV-GFP and AVP or PRV-GFP and OXT. In addition, in a separate group of five rats, Phaseolus vulgaris leucoagglutinin (PHAL), an anterograde tracer, was injected unilaterally into the PVN and cholera toxin beta subunit was microinjected into the tracheal wall. Analysis of five successfully infected animals showed that 14% of PRV-GFP labeled neurons express AVP traits and 18% of transneuronally-labeled neurons contain OXT. Furthermore, the identified AVPNs innervating extrathoracic trachea receive axon terminals of the PVN neurons. The results indicate that AVP- and OXT-producing PVN cells, via direct projections to the AVPNs, could modulate cholinergic outflow to the airways, as a part of overall changes in response to stress.

Arginine Vasopressin Alters Both Spontaneous and Phase-Locked Synaptic Inputs to Airway Vagal Preganglionic Neuron via Activation of V1a Receptor: Insights into Stress-Related Airway Vagal Excitation

“…Morphologically, AVP-containing fibers originating from the PVN project to the vicinity of AVPNs (Kc et al, 2006 ), and functionally, the results from our present study further certified that AVP do excite those AVPNs. AVP, as well as CRH (also excites the AVPNs, unpublished observation), is critically involved in the occurrence of psychological stress.…”

“…In psychological stress, arginine vasopressin (AVP) synthesized within the PVN is reported to be the initiator to trigger increased release of corticotrophin-releasing hormone (CRH) and subsequent activation of the hypothalamic-pituitary-adrenocortical (HPA) axis (Scaccianoce et al, 1991 ; Wotjak et al, 1996 ; Hatzinger et al, 2000 ); and the concentration of AVP is elevated in a stress level-dependent manner, in both plasma and cerebrospinal fluid (CSF; Bao et al, 2014 ). More precisely, AVP-containing fibers originating directly from the PVN are found just in the vicinity of AVPNs in the eNA (Kc et al, 2006 ). It has been widely accepted that AVP can act as a neuromodulator or transmitter mediating the alterations from central neuronal activities to psychological status (de Wied et al, 1993 ; Raggenbass, 2001 ; Keck, 2006 ).…”

Asthmatic Airway Vagal Hypertonia Involves Chloride Dyshomeostasis of Preganglionic Neurons in Rats

“…Airway vagal preganglionic neurons (AVPNs), as the final efferent neurons through which the brain controls airway vagal activity, are primarily located in the dorsal motor nucleus of the vagus, the compact and external formation of the nucleus ambiguus (NA), and the intermediate zone between the dorsal motor nucleus of the vagus and NA (Jordan, 2001;Haxhiu et al, 2005;Canning, 2006). AVPNs in the external formation of the NA (eNA) are thought to be particularly crucial in the vagal control of airway smooth muscle, since only this subset of neurons can cause an increase of airway resistance if experimentally stimulated (Haselton et al, 1992;Kc et al, 2006). AVPNs are intrinsically silent, and their activity relies entirely on their synaptic inputs including excitatory glutamatergic inputs and inhibitory γ-aminobutyric acid (GABA)-ergic and glycinergic inputs (Chen et al, 2007(Chen et al, , 2012.…”

Optimization of the Fluorescent Protein Expression Level Based on Pseudorabies Virus Bartha Strain for Neural Circuit Tracing

“…To depict the neural network, several tracers have been developed, such as Vesicular stomatitis virus and Herpes simplex virus type 1 (strain 129) can map the output information of a target brain region, while Rabies virus and Pseudorabies virus (PRV; Bartha strain) have the ability to reveal the input neural circuit. Among these tracers, the PRV Bartha strain is the only retrograde trans-multisynaptic tool, and it is indispensable to determining the input neural circuit of the CNS and PNS (Collins et al, 1999; Zhang et al, 2003; Kc et al, 2006; Zhao, 2008; Kirby et al, 2010; Gonzalez-Joekes and Schreurs, 2012; Chen et al, 2013; Griffiths, 2015; Yao et al, 2018; Jin et al, 2019).…”