Brainstem Dbh⁺ neurons control allergen-induced airway hyperreactivity

Area of Science:

• Neuroscience
• Immunology
• Respiratory Medicine

Background:

• Asthma is characterized by exaggerated airway constriction (hyperreactivity) upon allergen exposure.
• Vagal sensory neurons are implicated in allergen-induced hyperreactivity, but downstream pathways are unclear.

Purpose of the Study:

• To map the complete neural circuit involved in allergen-induced airway hyperreactivity from the lung to the brainstem and back.
• To identify specific neuronal populations and neurotransmitters mediating this response.

Main Methods:

• Utilized single-nucleus RNA sequencing and RNAscope assays in mice exposed to inhaled allergens.
• Employed ablation and chemogenetic techniques to assess the function of identified neuronal populations.
• Used viral tracing to map neuronal projections and investigated neurotransmitter roles with antagonists.

Main Results:

• Identified a specific population of Dbh+ neurons in the nucleus of the solitary tract (nTS) activated by allergens.
• Demonstrated that Dbh+ nTS neurons project to the nucleus ambiguus (NA).
• Showed that NA neurons relay signals to drive airway constriction, with noradrenaline identified as a key transmitter.

Conclusions:

• Defined a canonical neural circuit for allergen response, involving nTS and NA neurons.
• Highlighted the role of noradrenaline in transmitting signals between nTS and NA.
• Suggests potential for neural modulation therapies to control allergen-induced airway hyperreactivity.