Olfactory inputs modulate respiration-related rhythmic activity in the prefrontal cortex and freezing behavior

Andrew H Moberly,Minghong Ma,Janardhan P Bhattarai,Mary Schreck,Wenqin Luo,Larry S Zweifel

doi:10.1038/s41467-018-03988-1

Andrew H Moberly, Minghong Ma + Show 4 more

Open Access

https://doi.org/10.1038/s41467-018-03988-1

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Abstract

Respiration and airflow through the nasal cavity are known to be correlated with rhythmic neural activity in the central nervous system. Here we show in rodents that during conditioned fear-induced freezing behavior, mice breathe at a steady rate (~4 Hz), which is correlated with a predominant 4-Hz oscillation in the prelimbic prefrontal cortex (plPFC), a structure critical for expression of conditioned fear behaviors. We demonstrate anatomical and functional connections between the olfactory pathway and plPFC via circuit tracing and optogenetics. Disruption of olfactory inputs significantly reduces the 4-Hz oscillation in the plPFC, but leads to prolonged freezing periods. Our results indicate that olfactory inputs can modulate rhythmic activity in plPFC and freezing behavior.

Highlights

Respiration and airflow through the nasal cavity are known to be correlated with rhythmic neural activity in the central nervous system
A thermocouple was chronically implanted in the nasal cavity to monitor respiration and bipolar electrodes were implanted in the olfactory bulb (OB) to record local field potentials (LFPs) activity
Respiration patterns were markedly different during freezing compared to non-freezing periods as evidenced by power spectrum density estimates from thermocouple and OB LFP signals (Fig. 1b)

Summary

Introduction

Respiration and airflow through the nasal cavity are known to be correlated with rhythmic neural activity in the central nervous system. The rodent barrel cortex, prefrontal cortex, and hippocampus exhibit oscillations that are phase-locked with breathing and disrupted when peripheral olfactory signals are removed[12,13,14,15] Oscillations in these regions, representing spatially local activity, are modulated by the respiration-related rhythm. Low frequency oscillations can serve as a mechanism for longrange communication via synchronization of cortical and subcortical brain regions that are recruited during different behavioral states[17, 18] This mechanism is utilized during fear discrimination and fear expression when the prefrontal cortex, basolateral amygdala, and hippocampus dynamically interact to mediate appropriate behavior[19, 20]. Both OE ablation and OB inactivation lead to prolonged freezing periods in the conditioned fear retrieval paradigm, and the latter treatment increases baseline freezing

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