Abstract

Nasal breathing is a dynamic cortical organizer involved in various behaviors and states, such as locomotion, exploration, memory, emotion, introspection. However, the effect of sensory deprivation of nasal respiratory breath (NRD) on behavior remain poorly understood. Herein, general locomotor activity, emotion, learning and memory, social interaction, and mechanical pain were evaluated using a zinc sulfate nasal irrigation induced nasal respiratory sensory deprivation animal model (ZnSO4-induced mouse model). In the open field test, the elevated O-maze test, and forced swim test, NRD mice exhibited depressive and anxiety-like behaviors. In memory-associated tests, NRD mice showed cognitive impairments in the hippocampal-dependent memory (Y maze, object recognition task, and contextual fear conditioning (CFC)) and amygdala-dependent memory (the tone-cued fear conditioning test (TFC)). Surprisingly, NRD mice did not display deficits in the acquisition of conditional fear in both CFC and TFC tests. Still, they showed significant memory retrieval impairment in TFC and enhanced memory retrieval in CFC. At the same time, in the social novelty test using a three-chamber setting, NRD mice showed impaired social and social novelty behavior. Lastly, in the von Frey filaments test, we found that the pain sensitivity of NRD mice was reduced. In conclusion, this NRD mouse model showed a variety of behavioral phenotypic changes, which could offer an important insight into the behavioral impacts of patients with anosmia or those with an impaired olfactory bulb (OB) (e.g., in COVID-19, Alzheimer’s disease, Parkinson’s disease, etc.).

Highlights

  • Introduction iationsRespiration is an essential metabolic activity as it provides oxygen, which involves nasal breathing and mouth breathing

  • The airflow moves along the olfactory epithelium at the roof of the nasal cavity, triggering olfactory sensory neurons to respond to mechanical stimuli airflow via a cAMP cascade and to induce olfactory bulb (OB) neuronal oscillations, which lock to breathing cycles [5]

  • In the open field test, we found that the distance and shuttle times of the nasal respiratory sensory deprivation (NRD) mice in the central area were reduced, but the total distance and average speed in the open field had no significant difference

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Summary

Introduction

Respiration is an essential metabolic activity as it provides oxygen, which involves nasal breathing and mouth breathing. The respiratory drive is produced by conditional bursting pacemaker neurons in the brain stem [1]. Scientists discovered that nasal breathing is not constant and can be altered by various emotions [2], cognitive states [3]. Mammalian olfactory sensory neurons have dual functions as odor detectors and mechanical sensors for nasal breathing [5]. The airflow moves along the olfactory epithelium at the roof of the nasal cavity, triggering olfactory sensory neurons to respond to mechanical stimuli airflow via a cAMP cascade and to induce olfactory bulb (OB) neuronal oscillations, which lock to breathing cycles [5].

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