Dec 13th, 2024 - Sophie Bagur

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ESPCI Paris

The role of bodily feedback in prefrontal regulation of fear states

We have all introspectively sampled the tie between our body and our emotions and multiple lines of evidence demonstrate the tight correlations between brain–body interactions and affective states. However, the question of the specificity and causality of this link has remained unresolved since it was first epitomized by the historical James-Cannon debate. In the past few years, the possibility of manipulating bodily feedback in the mouse has driven insight into the underlying physiological mechanisms from multiple labs [1-3].

I will share our work investigating in mice how specific breathing-driven oscillations underlie specific states of fear and causally contribute to their regulation. During fear-related freezing, regular breathing entrains the olfactory bulb which in turn transmits this rhythm to the dorsomedial prefrontal cortex where it organizes neural activity. Blocking the feedback of the respiratory rhythm to the brain reduces mice’s ability to maintain prolonged states of freezing. Moreover we observed that breathing rate, as well as other bodily parameters, are heterogenous despite identical freezing behaviour and can “encode” threat proximity. Our analysis of prefrontal cortex neural activity shows that these neurons respond to specific breathing rates, thus displaying possible “interoceptive tuning curves”. I will discuss the possibility that this provides a mechanism to readout emotional state from bodily feedback.

[1] Bagur S, Lefort JM, Lacroix MM, de Lavilléon G, Herry C, Chouvaeff M, Billand C, Geoffroy H, Benchenane K. Breathing-driven prefrontal oscillations regulate maintenance of conditioned-fear evoked freezing independently of initiation. Nat Commun 2021 May 10;12(1):2605.

[2] Klein AS, Dolensek N, Weiand C, Gogolla N. Fear balance is maintained by bodily feedback to the insular cortex in mice. Science 2021 Nov 19;374(6570):1010-1015.

[3] Hsueh B, Chen R, Jo Y, Tang D, Raffiee M, Kim YS, Inoue M, Randles S, Ramakrishnan C, Patel S, Kim DK, Liu TX, Kim SH, Tan L, Mortazavi L, Cordero A, Shi J, Zhao M, Ho TT, Crow A, Yoo AW, Raja C, Evans K, Bernstein D, Zeineh M, Goubran M, Deisseroth K. Cardiogenic control of affective behavioural state. Nature 2023 Mar;615(7951):292-299.