Behavioral State-Dependent Modulation of Prefrontal Cortex Activity by Respiration

Respiration-rhythmic oscillations in the local field potential emerge in the mPFC, a cortical region with a key role in the regulation of cognitive and emotional behavior. Respiration-driven rhythms coordinate local activity by entraining fast γ oscillations as well as single-unit discharges. To what extent respiration entrainment differently engages the mPFC network in a behavioral state-dependent manner, however, is not known. Here, we compared the respiration entrainment of mouse PFC local field potential and spiking activity (23 male and 2 female mice) across distinct behavioral states: during awake immobility in the home cage (HC), during passive coping in response to inescapable stress under tail suspension (TS), and during reward consumption (Rew). Respiration-driven rhythms emerged during all three states. However, prefrontal γ oscillations were more strongly entrained by respiration during HC than TS or Rew. Moreover, neuronal spikes of putative pyramidal cells and putative interneurons showed significant respiration phase-coupling throughout behaviors with characteristic phase preferences depending on the behavioral state. Finally, while phase-coupling dominated in deep layers in HC and Rew conditions, TS resulted in the recruitment of superficial layer neurons to respiration. These results jointly suggest that respiration dynamically entrains prefrontal neuronal activity depending on the behavioral state.SIGNIFICANCE STATEMENT The mPFC, through its extensive connections (e.g., to the amygdala, the striatum, serotoninergic and dopaminergic nuclei), flexibly regulates cognitive behaviors. Impairment of prefrontal functions can lead to disease states, such as depression, addiction, or anxiety disorders. Deciphering the complex regulation of PFC activity during defined behavioral states is thus an essential challenge. Here, we investigated the role of a prefrontal slow oscillation that has recently attracted rising interest, the respiration rhythm, in modulating prefrontal neurons during distinct behavioral states. We show that prefrontal neuronal activity is differently entrained by the respiration rhythm in a cell type- and behavior-dependent manner. These results provide first insight into the complex modulation of prefrontal activity patterns by rhythmic breathing.