Acoplamento dos sinais frontais do cérebro à respiração de ratos durante repertório comportamental espontâneo no campo aberto

Abstract

Breathing is an essential rhythm of life, and the main system that terrestrial mammals use to smell the world around them. Breathing cycles passively carry odorant molecules that bind to the olfactory receptors of the olfactory epithelium, and each cycle is sufficient as a unit of odor sensation. It is also known today that breathing modulates activity in the brain. In 1942, work by Edgar Adrian showed that the rhythmic flux of air in the olfactory epithelium of hedgehogs generates oscillations in the olfactory bulb. Recent work in rodents has shown that neuronal oscillations synchronized to respiratory activity occur not only at the olfactory bulb but also across distant brain areas, from prefrontal and visual cortices to subcortical areas, such as the hippocampus and the amygdala. Intriguingly, these widespread respiratory brain rhythms are not continuously present. Instead, the coupling between neuronal activity and respiration across brain regions changes dramatically with time. Previous work also showed that the power of these respiration entrained oscillations is higher in frontal areas. To understand these dynamics, we simultaneously recorded depth video along with respiration (intranasal pressure) and distributed brain signals (anterior cingulate, prelimbic, medial orbital and parietal cortices and olfactory bulb) in 6 rats as they spontaneously behaved in an enriched open field arena (21 sessions of 30 minutes each). Animals displayed a rich set of behavior, ranging from immobility (putative sleep) to walking, grooming, rearing and object exploration. In this thesis, we will present and discuss results on the modulation by respiratory activity on low and high-frequency components of the local field potential (LFP) of the rats' frontal brain. We will show how the magnitude of this modulation is strongly dependent on the instantaneous respiratory rate of the rats and recording site. We found that all breathing frequencies modulate LFP activity in all areas, with higher modulation of low frequency LFP components in the olfactory bulb, and higher modulation of gamma LFP components in the medial orbitofrontal cortex. To better dissect possible modulations of entrainment strength, we detected and selected the behavioral state of the animals and quantified the LFP-respiration entrainment for each one. We found significant modulation of respiratory LFP components for all behaviors. We saw that grooming behavior has the highest modulation of frontal brain LFP by respiratory activity. The results presented here may help to understand a few pieces of this puzzle, and will raise more questions about how and when breathing modulates frontal brain activity.