Respiration-driven oscillations in emotional behaviour

• Applicant: Dr. Jonas-Frederic Sauer
• Subject Area: Cognitive, Systems and Behavioural Neurobiology
• Term: from 2018 to 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 407164792

Nasal respiration induces rhythmic fluctuations in the local field potential recorded in the brain. These respiration-related (RR) brain oscillations have been described in brain circuits involved in the processing of odor information. However, recent work, including our own, revealed that RR oscillations are also observed in brain regions responsible for the control of higher cortical functions including emotions. In a recent publication, we have shown that strong RR oscillations occur in the medial prefrontal cortex (mPFC) of awake mice. Prefrontal RR rhythms are coherent with nasal respiration and reach the mPFC via the olfactory system. Interestingly, preliminary work revealed that prefrontal RR oscillations are prominently observed during negative emotional states of despair and fear. Despair can be elicited in mice in a so-called tail suspension (TS) paradigm, in which the animals naturally try to escape but show intermittent epochs of immobility. These immobile periods are commonly interpreted as the animal ‘giving up’ the escape response, thus representing despair. This conclusion is backed up by published observations that antidepressant drugs reduce the time spent immobile in the TS paradigm. Fear memory, on the other hand, can be elicited by exposing mice to a context in which they had previously received mild foot shocks. Our finding of enhanced prefrontal RR oscillations during these negative emotional states thus suggests that RR rhythms might be involved in the expression of negative emotions. Furthermore, we demonstrate in preliminary work that RR oscillations occur in downstream brain areas involved in the behavioural expression of despair. Finally, RR oscillations contribute to the organization of neuron activity in mPFC and downstream regions such that neuronal action potentials occur predominantly during the rising phase of the RR rhythm during despair. Jointly, these data raise the intriguing possibility that RR rhythms might contribute to the behavioural realization of negative emotions by synchronizing neuronal discharges in distributed brain regions. In the proposed project we aim to test this hypothesis using in vivo electrophysiology and optogenetics applied to behaving mice. (1) We will characterize the coupling of prefrontal neuron discharges to RR oscillations during despair and fear. (2) We aim to dissect the impact of RR oscillations on brain-wide circuits related to despair behaviour. (3) We will examine whether neuronal spiking during the rising phase of RR activity is causally responsible for despair and fear behaviour. With this approach, we will reveal fundamental insights into the role of respiration-rhythms on brain activity during negative emotional states. Given the clinical relevance of affective disturbances such as depression or anxiety disorders, our results may also prove crucial for future research efforts understanding brain circuit dysfunction in psychiatric disease.

• DFG Programme: Research Grants